[gwasfilter: an R script to filter genome-wide association study].

Objective: To develop an R script that can efficiently and accurately filter genome-wide association studies (GWASs) from the GWAS Catalog Website. Methods: The selection principles of GWASs were established based on previous studies. The process of manual filtering in the GWAS Catalog was abstracted as standard algorithms. The R script (gwasfilter.R) was written by two programmers and tested many times. Results: It takes six steps for gwasfilter.R to filter GWASs. There are five main self-defined functions among this R script. GWASs can be filtered based on "whether the GWAS has been replicated" "sample size" "ethnicity of the study population" and other conditions. It takes no more than 1 second for this script to filter GWASs of a single trait. Conclusions: This R script (gwasfilter.R) is user-friendly and provides an efficient and standard process to filter GWASs flexibly. The source code is available at github (https://github.com/lab319/gwas_filter).

Correction of Hyperglycemia in Diabetic Rats With the Use of Microencapsulated Young Market Pig Islets.

OBJECTIVE: The aim of this work was to investigate the transplantation efficacy of microencapsulated young market pig islets in a diabetic rat model. METHODS: Islets were isolated and purified from young market pigs obtained from a local slaughterhouse. The islets were encapsulated in barium alginate and subjected to a glucose-induced insulin release functional assay in culture. Microencapsulated islets were transplanted into diabetic Sprague-Dawley rats and removed after 30 days for histologic examination. RESULTS: The mean islet equivalent (IEQ) yield per gram of digested tissue was 3,125 ± 617 IEQ/g after isolation and 2,618 ± 917 IEQ/g after purification, respectively. Host rats' blood glucose concentrations normalized (from 22.3 ± 2.7 mmol/L to 5.1 ± 0.67 mmol/L) following encapsulated islet transplantation. After graft removal, hyperglycemia recurred in the rats, indicating that the grafts were responsible for maintaining euglycemia. Histology revealed viable islets in the capsules 30 days after graft removal. Immunolabeling of insulin verified that ß-cells within the capsules remained well granulated. No fibrosis or immune cells were found in histopathology. CONCLUSIONS: Barium alginate encapsulation of young market pig islets can normalize glucose regulation in diabetic rats without fibrosis or an immunologic response.

[Predictive value of cardiac magnetic resonance-derived parameters on the improvement of left ventricular function in patients with acute viral myocarditis].

Objective: To evaluate the predictive value of cardiac magnetic resonance (CMR)-derived parameters on the improvement of left ventricular function in patients with acute viral myocarditis. Methods: Forty patients, who referred for acute viral myocarditis in our hospital from September 2011 to September 2015, were prospectively enrolled in this study.All patients were examined by CMR during hospitalization for acute viral myocarditis (baseline) and after 12 months.The CMR sequences include: two dimension steady state free precession, 2D SSFP; triple inversion recovery, triple IR; early gadolinium enhancement; phase sensitive inversion recovery turbo field echo, PSIR TFE. Results: Thirty out of 40 patients with susceptive acute viral myocarditis met the CMR criteria of acute viral myocarditis (Lake Louise Criteria) (LL+ ) and the other 10 patients did not meet the diagnostic criteria (LL-). Left ventricular ejection fraction (LVEF) values were significantly lower in LL+ group than in LL- group at baseline and at 12 months after discharge (P<0.01 or 0.05, respectively). The baseline left ventricular end-systolic volume index (LVESVI) was significantly higher in LL+ group than in LL- group (P<0.05) and was similar between the groups at 12 months follow up.Left ventricular end-diastolic volume index (LVEDVI )was similar between the two groups at baseline and at 12 months follow up.LVEF was significantly higher during 12 months follow up compared to baseline in LL+ group and remained unchanged in LL- group during the two time points.LVESVI and LVEDVI remained unchanged at baseline and during 12 months follow up both in LL+ and LL- groups (P>0.05). Results showed that LL+ , edema ratio (ER) positive and global relative enhancement (gRE) positive were associated with significant increase of LVEF at 12 months follow up.However, LL-, ER negative, gRE negative, late gadolinium enhancement(LGE) negative and LGE positive linked with unchanged LVEF at 12 months follow up (P>0.05). Patients were further divided into LVEF increase (ΔLVEF≥5%) group and non LVEF increase group (ΔLVEF<5%), the results of Chi-square test showed that LL+ and ER positive were related to the improvement of LVEF (P<0.05), while gRE and LGE were not associated with improvement of cardiac function (P>0.05). Multiple linear regression analysis, using ER, gRE and LGE as independent variables and LVEF as dependent variables, showed that the presence of myocardial edema was the strongest independent predictor of an increase in LVEF at follow up (full model: non-standardized coefficient 0.445, P=0.043; reduced model: non-standardized coefficient 0.442, P=0.12). Conclusion: Cardiac magnetic resonance imaging monitoring is valuable to observe the cardiac function and morphology changes in patients with acute viral myocarditis, and myocardial edema imaging is the most powerful parameter to predict the improvement of LVEF in this patient cohort.

[The effect and factors associated with outcome of extracorporeal membrane oxygenation in refractory cardiogenic shock patients].

Objective: To observe the clinical efficacy and factors associated with outcome of extracorporeal membrane oxygenation (ECMO) in refractory cardiogenic shock patients. Methods: Patients with refractory cardiogenic shock received ECMO treatment in our hospital from May 2013 to November 2015 were retrospectively analyzed. The clinical status before ECMO support, ECMO timing, complications and outcome were observed and analyzed.The hemodynamic data and the amount of vasoactive drugs at 2 hours before ECMO support and at 2, 6, 24 and 48 hours after ECMO support were collected and compared. Results: Ten refractory cardiogenic shock patients were included in this study (5 acute fulminant myocarditis patients, 4 acute myocardial infarction patients, 1 myocardial rupture patient (6 males, 4 females, age ranged 12 to 56 years). Before ECMO, the mean left ventricular ejection fraction (LVEF) was (31.4±10.2)%, the mean score of APACHE Ⅱ was 26.6±10.8. Eight patients developed cardiac arrests and the duration of CPR ranged from 10 to 300 minutes and three patients received IABP. CVP decreased, BP increased, HR decreased, ScVO2 increased, dose of dobutamine decreased at 2 hours after ECMO support. After ECMO support for 6 hours, lactate decreased, dose of norepinephrine decreased. After ECMO support for 24 and 48 hours, hemodynamics became stable and shock was significantly improved. Complication including infection of limb and catheterization site occurred in 3 patients, femoral arterial thrombosis occurred in 2 patients, critical limb ischemia occurred in 2 patients, hemorrhage at the catheterization site occurred in 2 patients. The duration of ECMO ranged from 2 to 220 hours. Nine patients could be weaned off ECMO support and 6 patients survived to hospital discharge. Two patients died due to too late ECMO support, the other two patients died due to severe complication of limb. Conclusions: ECMO can rapidly improve hemodynamic stability of patients with cardiogenic shock. Accurate assessing the timing of ECMO support and decreasing complication of limb play a critical role on improving outcome in refractory cardiogenic shock patients.

Disrupted Brain Connectivity Patterns in Patients with Type 2 Diabetes.

BACKGROUND AND PURPOSE: Type 2 diabetes is associated with an increased risk of dementia. This study investigated the global connectivity patterns in the brains of patients with type 2 diabetes by using a functional MR imaging technique. MATERIALS AND METHODS: Forty patients and 43 age-, sex-, and education-matched healthy controls underwent resting-state functional imaging in a 3T MR imaging unit. Degree centrality, a commonly used measurement of global connectivity, was computed for a full-brain exploration of the regions influenced by type 2 diabetes. We then examined the functional connectivity of each region by using the seed-based approach. Finally, voxelwise correlation analyses were performed to explore the relationship among the connectivity changes, cognitive performance, and diabetes-related variables. RESULTS: Patients exhibited decreased degree centrality in the left lingual gyrus and increased centrality in the right insula and dorsal anterior cingulate cortex (corrected P < .05). The occipital network anchored in the lingual gyrus showed extensively reduced connectivity, while the network connectivity of the insula and cingulate cortex (mostly included in the salience network) was significantly elevated (corrected P < .05). Correlational analyses revealed that in the diabetic group, impaired visual memory and executive function performance were correlated with occipital hypoconnectivity, while higher fasting plasma glucose levels and better executive functioning were related to anterior cingulate cortex hyperconnectivity (all corrected P values < .05). Similar effects were not detected in the controls. CONCLUSIONS: This preliminary study shows that network connectivity is altered in patients with type 2 diabetes, which may provide critical insight into the neural substrate of diabetes-related cognitive decline.

Optimization of pyrethroid and repellent on fabrics against Stegomyia albopicta (=Aedes albopictus) using a microencapsulation technique.

A new approach employing a combination of pyrethroid and repellent is proposed to improve the protective efficacy of conventional pyrethroid-treated fabrics against mosquito vectors. In this context, the insecticidal and repellent efficacies of commonly used pyrethroids and repellents were evaluated by cone tests and arm-in-cage tests against Stegomyia albopicta (=Aedes albopictus) (Diptera: Culicidae). At concentrations of LD50 (estimated for pyrethroid) or ED50 (estimated for repellent), respectively, the knock-down effects of the pyrethroids or repellents were further compared. The results obtained indicated that deltamethrin and DEET were relatively more effective and thus these were selected for further study. Synergistic interaction was observed between deltamethrin and DEET at the ratios of 5 : 1, 2 : 1, 1 : 1 and 1 : 2 (but not 1 : 5). An optimal mixing ratio of 7 : 5 was then microencapsulated and adhered to fabrics using a fixing agent. Fabrics impregnated by microencapsulated mixtures gained extended washing durability compared with those treated with a conventional dipping method. Results indicated that this approach represents a promising method for the future impregnation of bednet, curtain and combat uniform materials.

Percutaneous quadriceps tendon pie-crusting release of extension contracture of the knee.

To release extension contracture of the knee, the authors used a minimally invasive technique: percutaneous quadriceps tendon pie-crusting release. Percutaneous pie-crusting release was performed using an 18-gauge needle to puncture the stiff fibrous band of the distal and lateral quadriceps tendon under maximum knee flexion. Quadriceps contracture was gradually released by multiple needle punctures. A knee brace was prescribed for one week and knee flexion exercises were performed on the first postoperative day. This technique was performed in seven post-traumatic stiff knees and five stiff total knee arthroplasties. Mean maximum flexion increased from 37° preoperatively to 50° after arthrolysis and 107(o) after pie-crusting. At a mean follow-up of eight months, mean maximum flexion was 103°. There were no major complications. The technique of quadriceps tendon pie-crusting release is a simple, minimally invasive and effective treatment for knee extension contracture.

Expression pattern of tumour-associated antigens in hepatocellular carcinoma: association with immune infiltration and disease progression.

BACKGROUND: The distinct expression pattern of tumour-associated antigens (TAAs) might be a critical reason for the inefficacy of immunity-based treatments and heterogeneous postsurgical recovery in patients with solid tumours, including hepatocellular carcinoma (HCC). However, little is known about the clinical value of the coexpression patterns of multiple TAAs. METHODS: We determined the expression of multiple TAAs with identified immunogenicity (GPC3, AFP, SSX-2, NY-ESO-1, EpCAM, midkine) and the density of tumour-infiltrating immune cells by immunohistochemistry in a panel of 362 primary HCC patients. We evaluated the association between the TAAs, immune cell infiltration, clinicopathological parameters, and prognosis. RESULTS: Patients who coexpressed more TAAs had better prognosis (P<0.00001, overall survival). The integrated pattern of TAA was associated with good differentiation and small tumour size, and with more CD57(+) natural killer and CD20(+) B-cell infiltration (P<0.05). Multivariate Cox proportional hazards analysis identified the TAA index as an independent prognostic indicator (hazard ratio 0.625; 95% confidence interval 0.467-0.837; P=0.002), and could further predict patient prognosis in collaboration with local immune infiltration. CONCLUSION: Our results could provide new evidence for the improvement of prognostic molecular signatures in HCC, and a novel rationale for patient enrolment in future immunotherapeutic trials and/or clinical treatments.

Natural products with antitumor activity from endophytic fungi.

Endophytic fungi are a seemingly inexhaustible source of novel bioactive natural products. Currently, more than 140 fungal metabolites have shown confirmed activity in tumor cell line bioassays. We present the chemical structures of these antitumor metabolites, their corresponding fungal endophytes and host plants, and the activities they exhibited, and briefly discuss some of their action mechanisms. This review emphasizes the role of endophytic fungi as an important source of leads for drug discoveries.

PI3K/Akt/mTOR pathway inhibitors in cancer: a perspective on clinical progress.

The phosphoinositide 3-kinase (PI3K)/serine-theronine protein kinase Akt (also known as protein kinase B (PKB))/mammalian target of rapamycin (mTOR) pathway is a vital transduction cascade that is connected with many essential cellular activities, such as growth and survival. Along with extensive pharmacological studies validating the therapeutic potential of targeting the PI3K/Akt/mTOR pathway for the treatment of cancer, kinase inhibitors targeting significant knots of this pathway including PI3K, Akt, mTOR, and 3-phosphoinositide-dependent protein kinase-1 (PDK-1) keep arising and entering clinical studies. Herein, we review the most up-to-date landscape on developing small-molecule kinase inhibitors targeting the PI3K/Akt/mTOR pathway, with emphasis on small-molecule inhibitors which have been progressed into clinical studies.

CK19 mRNA expression in the bone marrow of patients with esophageal squamous cell carcinoma and its clinical significance.

The 5-year survival rate in resectable patients with esophageal cancer is only 20% to 36%. Regional relapse and distant metastasis are responsible for the failure of treatment and the majority of cancer-related deaths. Earlier detection of metastases, especially micrometastases, has the potential for more accurate risk stratification in subsequent therapy decisions. No effective techniques have yet been found to detect metastases in erroneously thought to have early stage disease. This study was designed to investigate the clinical significance of bone marrow micrometastases detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in patients with esophageal cancer. Expression of CK19 mRNA in the bone marrow of 61 patients with esophageal squamous cell carcinoma (ESCC) and 15 benign pulmonary and esophageal disease patients was assessed via RT-PCR. Correlation of CK19 mRNA expression to the clinicopathologic features and prognosis of the 61 patients was analyzed: 21.3% (13/61) were positive for expression of CK19 mRNA in patients with ESCC. No CK19 mRNA was detected of the 15 benign pulmonary and esophageal disease patients. CK19 mRNA expression did not correlate with the clinicopathologic features of the patients with ESCC, but patients with CK19 mRNA-positive bone marrow had earlier recurrence and shorter survival after surgery. In multivariate analysis, CK19 mRNA was found to be an independent predictor of a poor outcome. CK19 mRNA may be used as a molecular maker to detect bone marrow micrometastases in patients with ESCC and may help to select the proper therapy and predict the prognosis.

Inhibitive effect of diphenytriazol on rat cytochrome P450 enzyme in vitro.

The inhibiting effect of diphenytriazol, a non-hormonal early pregnancy-terminating agent, towards cytochrome P450 (CYP) enzymes in rat liver microsomes was studied in vitro. The inhibiting effect of diphenytriazol on CYP was investigated by coincubating diphenytriazol with the specific CYP1A substrates, ethoxyresorufin and phenacetin, in microsome induced by beta-naphthoflavone, with the specific CYP2B substrates, pentoxyresorufin and aminopyrine, in the microsome induced by phenobarbital, and with the specific CYP3A substrates, diazepam, testosterone, nifedipine and quinine sulfate in microsome induced by dexamethasone. The results showed that diphenytriazol inhibited the metabolism of ethoxyresorufin and phenacetin significantly, and its inhibition potential on CYP1A was higher than the typical inhibitor fluvoxamine. Diphenytriazol also inhibited the metabolism of diazepam, testosterone, nifedipine and quinine sulfate to different degrees, but its inhibition potential was relatively weaker than that of the typical inhibitor, ketoconazole. No inhibiting effect of diphenytriazol was seen on the metabolism of pentoxyresorufin and aminopyrine. The ability of diphenytriazol to inhibit rat liver CYP1A and CYP3A suggests that in human patients complex interactions may result from co-adiministration of diphenytriazol with other agents which are also substrates for CYP1A or CYP3A enzymes.

Synthesis and cytotoxic activity of 3-phenyl-2-thio-quinoxaline 1,4-dioxide derivatives in hypoxia and in normoxia.

A series of novel 3-phenyl-2-ethylthio/ethylsulfinyl/ethylsulfonyl/phenylthio/ phenylsulfonyl-quinoxaline 1,4-dioxide derivatives were synthesized and screened for their cytotoxicity in vitro on human leukaemia cell line HL-60, human esophagus cancer cell line ECA-109, human prostate cancer cell line PC-3, human gastric carcinoma cell line SGC-7901, and human breast cancer cell line MCF-7 in hypoxia and in normoxia. Half of tested compounds showed higher cytotoxic activity both in hypoxia and in normoxia. The mechanism of one potent compound, 67, in hypoxia showed that the mitochondria pathway is involved in the antitumor activity of this class of compounds.

Gender differences in limonin pharmacokinetics in rats.

In the present study, the pharmacokinetics of limonin (LM) were investigated in male and female rats. LM concentrations in the plasma were determined after the oral administration of 36 mg/kg LM or after intravenous (i.v.) injection of LM 3.6 mg/kg respectively. Concentrations in the tissues, urine, feces and bile were also analyzed following the oral administration of 36 mg/kg of the test product. It was found that the plasma concentrations of LM in female rats were significantly higher (P < 0.01) than those in male rats. Assessment of the effects of limonin based on the C(max) and AUC in female rats showed that levels were about 50-fold higher than those in male rats after oral administration of 36 mg/kg LM. Furthermore, after i.v. administration of 3.6 mg/kg LM, the C(max) and AUC in female rats was found to be about 3-fold higher than those in male rats. The total excretion of LM in the urine and bile of female rats was also found to be significantly higher than in male rats, which displayed lower concentrations of LM in the tissues, amounting to around one-half to one-tenth of those in female rats, apart from levels in the rectum and duodenum. In conclusion, the present results demonstrate the existence of marked gender difference in LM pharmacokinetics in rats.

Crowded Cu(I) complexes involving benzo[h]quinoline: pi-stacking effects and long-lives excited states.

The Friedländer condensation was employed to synthesize two series of 3,3'-polymethylene bridged ligands, L, based on 2-(2'-pyridyl)-benzo[h]quinoline and 2,2'-bibenzo[h]quinoline (BHQ) along with the fully aromatic naphtho[1,2-b]-1,10-phenanthroline. Complexes [Cu(L)(2)](+) were prepared as their perchlorate or hexafluorophosphate salts. The solution state structures were analyzed by NMR and shielding effects reflected significant interligand pi-stacking interaction in the complexes. Solid-state structures of the complexes where L = 3,3'-tetramethylene-2,2'-bibenzo[h]quinoline or naphtho[1,2-b]-1,10-phenanthroline were determined by X-ray analysis. The tetramethylene bridged complex showed a highly distorted coordination geometry with the BHQ rings of opposing ligands pi-stacked at a interplanar distance of about 3.37 A. Complexes of the BHQ series showed a pronounced MLCT absorption maximum which shifted bathochromically from 496 to 610 nm as the 3,3'-bridge decreased from 4 to 2 carbons. The BHQ complexes luminesced strongly in CH(2)Cl(2) solution and the tetramethylene-bridged system showed the longest yet recorded excited-state lifetime for a copper MLCT excited state, tau = 5.3 micros and Phi = 0.10.

Evaluation of diimine ligand exchange on Cu(I).

Four ligands have been prepared, 8,8-dimethyl-6,7,9-trihydropyrido[1,2-b]acridine and three 4,4',6,6'-tetrasubstituted derivatives of 2,2'-bipyrimidine where the substituents are methyl, phenyl, and p-tolyl. The corresponding [CuL(2)](+) salts of these ligands evidence nonequivalent NMR signals that allow an estimation of the ligand exchange barrier in both acetonitrile and chloroform solution. Lower barriers are found in the former solvent and attributed to solvent participation in the exchange process. Corresponding differences in the oxidation potentials of the complexes are explained in a similar manner. The electronic absorption properties of the complexes are also consistent with the steric and electronic properties of the ligands. [Cu(2c)(2)](PF(6)), where 2c = 4,4',6,6'-tetraphenyl-2,2'-bipyrimidine, was analyzed by X-ray diffraction and found to crystallize in the space group Pccn with a = 14.761(2) A, b = 15.007(2) A, c = 24.407(4) A, and Z = 4. The internal and external phenyl rings are disposed quite differently, with the internal rings interacting strongly with the orthogonal ligand.

[Inhibitory effect of genistein on the proliferation of the anterior pituitary cells of rats].

The effects of tyrosine kinase inhibitor genistein on the proliferation of rat anterior pituitary cells and mouse AtT-20 cells were studied using techniques of cell culture, 3H-TdR incorporation, flow cytometric analysis and electron microscope. Genistein significantly inhibited the proliferation of rat anterior pituitary cells and mouse AtT-20 cells. Genistein (50 and 100 mumol/L) blocked the proliferation of AtT-20 cells at G0/G1 and G2/M phases and evoked an apoptotic peak of these cells with an apoptotic ratio of 19.9% and 36.4%. The apoptotic cells were also observed under the electron microscope. In consequence, genistein, as a tyrosine kinase inhibitor, can significantly inhibit the proliferation of pituitary cells possibly by inducing apoptosis, and the tyrosine kinase activity may play a key role in the proliferation and differentiation of pituitary cells.

Direct comparison of electron transfer properties of two distinct semisynthetic triads with non-protein based triad: unambiguous experimental evidences on protein matrix effects.

In order to understand the roles of protein matrix in electron transfer processes (ET) within biological systems, a heme-based donor (Zn-heme: ZnPP)-sensitizer (Ru2+(bpy)3)-acceptor (cyclic viologen: BXV4+) triad 1 was used as a probe molecule. Two semi-synthetic systems, Cyt-b562(1) and Mb(1), in which the triad is incorporated into cytochrome b562 (Cyt-b562) or into myoglobin (Mb), were constructed by cofactor reconstitution. These two semi-synthetic proteins were compared with the triad itself (i.e., without the protein matrix) using absorption spectroscopy, steady state emission and excitation studies, laser flash photolysis experiments, and molecular modeling. Photoexcitation of the ZnPP moiety of Cyt-b562(1) or Mb(1) leads to a direct ET from the triplet state of ZnPP state (3ZnPP) to BXV4+ to generate a final charge-separated (CS) state, Cyt-b562(Zn+)-Ru2+-BXV3+* or Mb(Zn+)-Ru2+-BXV3+*. On the other hand, direct ET from the excited ZnPP moiety to the BXV4+ moiety is also involved in 1 in the absence of the protein matrix, but the excited state of ZnPP involved is not 3ZnPP, but the singlet excited state (1ZnPP) in this pathway. When the Ru2+(bpy)3 moiety of Cyt-b562(1) or Mb(1) is excited, a stepwise ET relay occurs with the ion-pair, Cyt-b562(Zn)-Ru3+-BXV3+* or Mb(Zn)-Ru3*-BXV3+*, as an intermediate, leading to the same final CS state as that generated in the direct ET pathway. The lifetimes of the corresponding final CS states were determined to be 300 ns for 1 in the absence of the protein matrix, 600-900 ns for Cyt-b562(1) and 1.1-18 micros for Mb(1), the values of which are greatly affected by the protein matrix. Molecular modeling study of the three systems consistently explained the differences of their photophysical behavior.

[Effect of interleukin 2 on the expression of estrogen receptors in the anterior pituitary of rats].

Using primary serum-free cell culture combined with immunocytochemistry and semi-quantified RT-PCR methods, we observe the modulation of estrogen receptor alpha (ERalpha) and beta (ERbeta) by interleukin-2 (IL-2) in rat anterior pituitary. The results show that IL-2 up-regulates the level of ERalpha protein and the expression of ERalpha mRNA, but down-regulates those of ERbeta. The density per cell of ERalpha-immunoreactive (ir) cells increases from 48.740 4.567 to 81.188+/-6.619, whereas that of ERbeta -ir cells decreases from 102.560+/-6.250 to 72.718+/-7.623 after rhIL-2 (10 microgram/L) incubation for 48 h. In parallel with these changes, the ratio of ERalpha/ beta -actin mRNA increases from 0.1511 to 0.4334, and ERbeta /beta -actin mRNA declines from 0.3822 to 0.1528. It is likely that IL-2 has direct regulatory effect on ER in anterior pituitary.

[Interleukin-2 stimulates the proliferation of cultured RC-4B/C pituitary adenoma cell line].

The aim of the present study was to investigate whether interleukin-2 (IL-2) is involved in the proliferation control of the cultured RC-4B/C cell, which is a derived pituitary adenoma cell line of the rat. The level of cell proliferation was estimated by assessing (3)H-thymidine ((3)H-TdR) incorporation rate. IL-2 (10 1000 U/ml) significantly stimulated (3)H-TdR incorporation into the cell line in a dose-dependent manner. Specific PTK inhibitor tyrphostin (1 micromol/L) suppressed RC-4B/C cell proliferation and blocked the effect of IL-2 on RC-4B/C cells. After the PKA signaling pathway was inhibited by specific PKA inhibitor H-9 (1 micromol/L), the proliferation rate of RC-4B/C cells increased significantly. H-9 also enhanced the stimulation of IL-2 on RC-4B/C cell growth. Anti-estrogen tamoxifen (1 micromol/L) had no significant effect on the action of IL-2 on the proliferation of RC-4B/C cells. In conclusion, it is suggested that IL-2 modulates the proliferation of the cultured RC-4B/C pituitary adenoma cell line, and the action is closely related with the PTK and PKA signaling pathway.