ABSTRACT
Dysfunction of the Hippo pathway enables cells to evade contact inhibition and provides advantages for cancerous overgrowth. However, for a significant portion of human cancer, how Hippo signaling is perturbed remains unknown. To answer this question, we performed a genome-wide screening for genes that affect the Hippo pathway in Drosophila and cross-referenced the hit genes with human cancer genome. In our screen, Prosap was identified as a novel regulator of the Hippo pathway that potently affects tissue growth. Interestingly, a mammalian homolog of Prosap, SHANK2, is the most frequently amplified gene on 11q13, a major tumor amplicon in human cancer. Gene amplification profile in this 11q13 amplicon clearly indicates selective pressure for SHANK2 amplification. More importantly, across the human cancer genome, SHANK2 is the most frequently amplified gene that is not located within the Myc amplicon. Further studies in multiple human cell lines confirmed that SHANK2 overexpression causes deregulation of Hippo signaling through competitive binding for a LATS1 activator, and as a potential oncogene, SHANK2 promotes cellular transformation and tumor formation in vivo. In cancer cell lines with deregulated Hippo pathway, depletion of SHANK2 restores Hippo signaling and ceases cellular proliferation. Taken together, these results suggest that SHANK2 is an evolutionarily conserved Hippo pathway regulator, commonly amplified in human cancer and potently promotes cancer. Our study for the first time illustrated oncogenic function of SHANK2, one of the most frequently amplified gene in human cancer. Furthermore, given that in normal adult tissues, SHANK2's expression is largely restricted to the nervous system, SHANK2 may represent an interesting target for anticancer therapy.
ABSTRACT
Objective To investigate the characteristic sonographic and pathological features of breast ductal carcinoma in situ (DCIS) without microcalcifications on mammography (MG).Methods Forty cases of DCIS without microcalcifications on MG were retrospectively reviewed.The 40 lesions were classified into mass and non-mass groups according to their sonographic findings.The pathological subtypes and nuclear grades of these cases were also analyzed.Fisher exact test was used to compare the differences of the sonographic accuracy rate,sonographic microcalcification rate,pathological nuclear grade and subtype rate between mass and non-mass groups.Results No abnormal finding was found in sixteen cases (40.0％)on MG and only one case (2.5％) on ultrasonography (US),respectively.The most common sonographic feature of DCIS without microcalcifications on MG were masses (75.0％,30/40),and other sonographic findings were round/oval and irregular shape,microlobulated margin,heterogeneous hypoechogenicity and isoechogenicity,and posterior acoustic feature.Ductal dilatations and heterogeneous isoechogenicity were present in most non-mass lesions of DCIS without microcalcifications on MG (22.5％,9/40).The ultrasonographic microcalcifications were found in 5 cases of DCIS without microcalcifications on MG.The common pathological features of DCIS without microcalcifications on MG were medium-low nuclear grade (85.0％,34/40) and noncomedo (87.5％,35/40).The difference of US accuracy rate in mass and non-mass groups was statistically significant [73.3％ (22/30) vs 33.3％ (3/9),P=0.047].The differences of US microcalcification rate,pathological subtype and nuclear grade were not significant (P=1.000,0.070).Conclusions The mass appearance and medium-low nuclear grade were most common sonographic findings and pathological features of DCIS without microcalcifications on MG.Ultrasonography should be an helpful tool for improving the diagnostic sensitivity ofmammography in breast DCIS.
ABSTRACT
OBJECTIVE:To establish a method for simultaneous determination of residual methylparaben,ethylparaben,nipa-sol and benzalkonium chloride in marketed eye drops. METHODS:HPLC method was adopted. The determination was performed on Hypersil GOLD C18 column with mobile phase consisted of 0.005 mol/L ammonium acetate(10 mL triehtylamine in 1 L solu-tion,pH adjusted to 5.0±0.5 with glacial acetic acid)-acetonitrile(45:55,V/V)at the flow rate of 1.0 mL/min. The detection wave-length was 262 nm(methylparaben,ethylparaben,nipasol)and 214 nm(benzalkonium chloride),respectively. The column tem-perature was 30 ℃ and sample size was 20 μL. RESULTS:The linear range were 1.2350-15.4380 μg/mL for methylparaben(r=0.9999),1.3170-16.3836 μ g/mL for ethylparaben (r=0.9997),1.2072-15.0894 μ g/mL for nipasol (r=0.9996) and 17.776-222.0 μg/mL for benzalkonium chloride(r=0.9999),respectively. Limits of quantitation were 2.0,2.0,2.0,1.11 μg,re-spectively;limits of determination were 0.375,0.375,0.375,0.333 μg,respectively. RSDs of precision,stability and reproducibili-ty tests were all lower than 2.0%. The average recoveries were 98.14%-102.48%(RSD=1.6%,n=9),98.79%-102.42%(RSD=1.3%,n=9),98.19%-102.49%(RSD=1.5%,n=9)and 98.76%-100.53%(RSD=0.6%,n=9),respectively. CONCLUSIONS:The method is accurate,reproducible,simple and suitable for the determination of residual methylparaben,ethylparaben,nipasol and benzalkonium chloride in marketed eye drops.
ABSTRACT
Objective To retrospectively assess the diagnostic value of nuchal translucency (NT) thickness and facial profile ultrasonic markers [including frontomaxillary facial (FMF) angle,and the ratio of prenasal thickness to nasal bone length (PT/NBL)] for trisomy 21 syndrome in first-trimester fetuses.Methods Ultrasonograhic images of 35 fetuses with trisomy 21 syndrome and 70 gestational age matched normal fetuses were analyzed in first-trimester.NT,FMF angle and the PT/NBL ratio were measured retrospectively in stored images from digital database between January 2012 and December 2015.The diagnostic value of NT,FMF angle and PT/NBL ratio were compared with different combinations.Results (1) The mean NT was significantly higher in the trisomy 21 group than that in controls (t =7.401,P =0.00).The NT above 2.5mm was observed in 20 trisomy 21 fetuses (57.1％) and in 3 normal fetuses (4.3％).(2) The mean FMF angle was significantly higher in the trisomy 21 group than that in controls (t =-5.283,P =0.00).The FMF angle above the 95th percentile (93.6°) was observed in 13 trisomy 21 fetuses (37.1％) and in 1 normal fetus (1.4％).(3) The mean PT/NBL ratio was significantly higher in the trisomy 21 group than that in controls (t =-7.826,P =0.00).The PT/NBL ratio above the 95th percentile (0.93) was observed in 19 trisomy 21 fetuses (54.3％) and in 4 normal fetuses (5.7％).(4) The sensitivity and Youden index for trisomy 21 increased gradually,which were 57.1 ％ and 0.528 by using NT,and 74.3％ and 0.686 by using NT and FMF angle,and 91.4％ and 0.828 by using NT,FMF angle and PT/NBL ratio.There were significant differences in the detection rates of trisomy 21 among the three strategies,while the diagnostic specificity of the three strategies were more than 90％.Conclusions The three parameters are significantly increased in trisomy 21 fetus in first-trimester.First,increased NT was most commonly detected,followed by increased PT/NBL ratio,and increased FMF angle again.Detection rates for trisomy 21 fetuses in first-trimester by ultrasound screening can be significantly improved if combination of all three parameters rather than just one parameter are performed.
ABSTRACT
Objective To evaluate the clinical significance of high frequency ultrasonography in the diagnosis of annular pancreas in neonates.Methods Ultrasound results,clinical data,operation results and complicating deformity of 19 neonates were reviewed retrospectively.The digestive tracts of 19 neonates,including stomach,duodenum,jejunoileum and colon,were examined with 8-12 MHz linear transducer before surgery.Results Of 19 neonates with annular pancreas,17 cases were diagnosed with ultrasound,the diagnostic rate was 89％.The pancreas tissue encircling the descending duodenum was directly displayed as a direct sign of ultrasonography and the expansion of the proximal end of the duodenum was presented as an indirect sign of ultrasonography in 17 neonates.There were 3 neonates with annular pancreas complicating intestine malrotation and 2 neonates with annular pancreas complicating duodenal membraneous stenosis.One neonate was misdiagnosised and the other was missed.Conclusions High frequency ultrasonography plays an important role in diagnosing annular pancreas and other digestive deformity in neonates.It can be used as the first choice for the neonatal annular pancreas.
ABSTRACT
Objective To compare high-frequency ultrasonography and MRI in diagnosis of medial patellofemoral ligament (MPFL) injury after acute lateral traumatic patellar dislocation(LTPD).Methods According to surgical data of 35 patients with acute LTPD,the incidence and sites of MPFL injury were analyzed.Further,based on high frequency ultrasonography and MRI data,the sensitivity,specificity and accuracy of high-frequency ultrasonography and MRI in different MPFL injuries were analyzed and compared.Results Among 35 patients,there were 21 cases with complete MPFL tear and 14 cases with partial MPFL tear.Tear of MPFL at the femoral attachment in 19 cases,at the patellar attachment in 15 cases,and at the mid-substance in 1 case.The sensitivity,specificity,accuracy of high-frequency ultrasonography diagnosis were 78.6％,95.2％,88.6％ respectively on partial MPFL tear and 95.2％,78.6 ％,88.6 ％ respectively on complete MPFL tear.The sensitivity,specificity,accuracy of MRI diagnosis were 85.7％,90.5％,88.6％ respectively on partial MPFL tear and 90.5％,85.7％,88.6％ respectively on complete MPFL tear.There were no significant difference between high-frequency ultrasonography and MRI in diagnosis of partial and complete MPFL injury (x2 =0.243,0.267; P =0.622,0.599).Conclusions MPFL formoral attachment is most vulnerable to damage,followed by patellar attachment.High-frequency ultrasonography,as well as MRI,can be used clearly to diagnose MPFL injury and accurately classify the damage,and it is also an easy,reliable,rapid method,which can be applied routinely to diagnose MPFL injury after actue LTPD.
ABSTRACT
Objective To explore the characteristics and the clinical application of MR perfusion weighted imaging(PWI)in the normal kidneys and the renal diseases.Methods Thirty-one subjects including 9 cases without urinary diseases,14 cases with renal carcinoma,6 cases with renal cyst and 2 cases witll renal tuberculosis who had been examined with T1WI,T2WI and PWI were analyzed retrospectively.All the data were processed by a workstation to obtain time-signal intensity curves,color perfusion maps and relative perfusion value.The relative renal blood volume(RBV),relative renal blood flow(RBF),mean transition time(MTT)and the time to peak(TTP)in the normal renal cortex and medulla and the renal lesions were calculated.Comparisons between the right and the left normal kidneys,and between the cortex and the medulla of the normal kidneys were performed using t test,and comparisons between the normal and the abnormal kidneys were performed using q test.Results Relative RBV and relative RBF of the cortex were 1.33±0.08 and 1.44±0.09 respectively,and for medulla were 0.58±0.05 and 0.78±0.13 respectively(t=9.2241 and 5.0336,P＜0.01);MTT(1.11±0.08)and TTP (1.04±0.06)of the cortex has no difference with that of the medulla(0.97±0.04 and 0.94±0.03)in the normal kidneys(t=2.2551 and 2.2613.P＞0.05).The values of relative RBF of the renal carcinoma (1.35±0.34)were significantly higher than that of the normal tissues(1.02±0.06)(q=3.0882,P＜0.01).Conclusion PWI is able to demonstrate the hemodynamic change of the normal renal tissues and the renal lesions,and it maybe an ideal method for showing the functional changes of the kidney and for differentiating the renal diseases.
ABSTRACT
Objective To study MR imaging manifestations of the mesorectum and mesorectal fascia. Methods 100 cases were divided into five groups according to the age. All MR images were retrospectively observed and analyzed by two radiologists.The observing contents included: ①exhibition of the mesorectal fascia, ②the signal intensity of the mesorectum and the pelvic fat and ③the thickness ratio of the mesorectum and the subcutaneous fat in different ages. All data were dealed with SPSS 10.0 software. Results The showing rate of the anterior, posterior, left and right mesorectal fascia respectively were 77, 100, 91 and 93 by MR imaging. The signal intensity of the mesorectum(550.8843) was significantly higher than that(469.8693) of pelvic fat in all five groups(P﹤0.05) and the signal difference between the mesorectum and the pelvic fat could be detected by naked eye. The thickness of the mesorectum and the subcutaneous fat had no association with ages.Conclusion MRI can display the mesorectum and mesorectal fascia clearly. The signal intensity of the mesorectum is significantly higher than that of pelvic fat in five groups. The thickness of the mesorectum and the subcutaneous fat have no association with ages.
ABSTRACT
Objective To assess the role of dynamic contrast-enhanced MRI for diagnosis and differential diagnosis of prostatic cancer. Methods Six volunteers, 32 patients with benign prostatic hyperplasia and 13 patients with biopsy-proven prostatic cancer underwent MR imaging. Dynamic MR with Gd-DTPA (gadolinium-diethylene triamine pentaacetic acid) bolus enhancement was performed followed by post-contrast T 1-weighed imaging. The signal intensive value in dynamic MRI was measured and calculated to draw the time-signal intensity curve of normal peripheral zone, prostatic cancer and benign hyperplasia. Results In dynamic MRI, the normal peripheral zone were enhanced mildly and slowly. The lesion enhancement of benign prostatic hyperplasia in 32 patients were obvious in early phase (60 s) and strengthened gradually, and then went to decrease in late phase (240 s) after peak value. The lesions in 9 of 13 cases with prostate cancer were enhanced obviously in early phase (60 s) and washed out rapidly in late phase, and the peak value was located on early phase. Conclusions In dynamic MRI, the enhancement of normal peripheral zone, prostate cancer and benign hyperplasia were different significantly. Dynamic MRI was very useful in the diagnosis and differentiation of prostate cance.
ABSTRACT
Objective To explore the diagnostic value of multiplanar reconstruction(MPR)of spiral CT in the disorders of lumbar intervertebral discs.Methods Fourty-one cases with the disorders of lumbar intervertebral discs were examined with conventional CT scans and MPR of spiral CT.CT findings of intervertebral discs at L 3/4 ,L 4/5 and L 5/S 1 were compared and observed.Results The conventional scans showed bulging and /or herniation of intervertebral discs in 35 cases,and normal in 6 cases which compression of nerveroots by intervertebral discs or osseous narrow of intervertebral discs were showed on MPR.The MPR showed compression of nerve roots,compression of dural sac or osseous narrow of intervertebral foramens in 36 cases.Conclusion MPR possesses important value in diagnosing the disorders of lumbar intervertebral discs,showing the causes of lumbar vertebral diseases and distinguishing the various diseases of lumbar vertebrae.
ABSTRACT
Objective To evaluate the value of MR-guided neurolytic celiac plexus block(NCPB)for treatment of upper abdominal cancer pain.Methods 13 neurolytic celiac plexus blocks were carried out in 12 patients with severe upper abdominal pain caused by malignant tumors.The pain-relieving effect of the block was both evaluated using visual analogue scale(VAS) and analyzed statistically in all cases.Results The placement of the needle MR-guided was easy and accurate,the successful rate of the puncture was 92%.There were no severe complications.The pain before and after the procedure had obvious difference and the pain relief could last for a long time.Conclusion MR-guided NCPB is a simple and effective technique for treatment of upper abdominal cancer pain.