[Efficacy of venetoclax-based induction regimen in newly diagnosed pediatric acute myeloid leukemia].

Objective: To explore the efficacy of venetoclax-based induction regimen for children with newly diagnosed acute myeloid leukemia (AML). Methods: Children with newly diagnosed AML in Beijing Children's Hospital Affiliated to Capital Medical University and Baoding Hospital Affliliated to Capital Medical University from November 2019 and December 2023 were prospectively included. The patients were divided into DAH group (daunorubicin, cytarabine and homoharringtonine) and VAH group (venetoclax, cytarabine and homoharringtonine) according to induction regimen. The clinical data of the children were collected, the clinical characteristics and induced remission rate between the two groups were compared, and multivariate logistic regression was used to analyze the related factors affecting the induced remission rate. Results: A total of 135 patients were enrolled, including 96 cases in the DAH group (54 males and 42 females), aged [M (Q1, Q3)] 6.4 (3.9, 11.6) years and 39 cases in the VAH group (26 males and 13 females), aged 8.0 (6.2, 13.2) years. Among patients initially diagnosed with low-medium risk AML, the morphologic complete remission rates were 94.7% (18/19) in the VAH group and 84.4% (38/45) in the DAH group, respectively, and the negativity conversion rates of minirnal residual disease (MRD) were 57.9% (11/19) and 46.7% (21/45), respectively, with no statistically difference (all P>0.05). Among patients initially diagnoised with high-risk AML, the morphologic complete remission rates in the VAH group was higher than that in the DAH group [95.0% (19/20) vs 70.6% (36/51), P=0.027], and negativity conversion rates of MRD were 45.0% (9/20) and 33.3% (17/51), respectively, with no statistically difference (P=0.359). The induction regimen (venetoclax, cytarabine and homoharringtonin) was beneficial to morphological remission (OR=0.126, 95%CI: 0.025-0.629). FLT3 mutation was not conducive to morphological remission (OR=5.832, 95%CI: 1.778-19.124) and negative MRD (OR=4.166, 95%CI: 1.396-12.433). Conclusion: Venetoclax-based induction regimen is more effective than traditional chemotherapy regimen for newly diagnosed pediatric AML.

A case of synovial chondromatosis of the knee with 87 free bodies and review of literature.

BACKGROUND: Synovial chondromatosis is a non-malignant synovial disorder characterized by the presence of cartilage formation within the synovial membrane, leading to the emergence of multiple cartilaginous nodules that may be either attached or unattached. The presence of this anatomical feature is frequently observed in articulations such as the knee, hip, elbow, and ankle. CASE REPORT: In this study, we present a case of synovial chondromatosis in the knee joint of a healthy male in his early 60s. Notably, the patient exhibited the simultaneous presence of 87 large loose bodies. The occurrence of a substantial quantity of unattached entities of notable dimensions within the joint is highly uncommon. CONCLUSIONS: The patient had several synovial chondromas, a rare disease. Synovial chondromatosis is a benign disorder; however, growing synovium can cause pyogenic cartilage nodules. Most loose bodies in joints can abrade and degenerate articular cartilage, causing long-term discomfort. Thus, an early-stage procedure to remove loose bodies and carefully excise synovial tissue is necessary to treat this condition.

[Clinical characteristics and prognosis of 28 cases of infant acute lymphoblastic leukemia].

Objective: To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL). Methods: A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children's Hospital, Capital Medical University and Baoding Children's Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients. Results: Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) (χ2=1.88, 1.47, P=0.170, 0.224). Conclusions: Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

[Impact of endoscopic endonasal approach on quality of life in patients with anterior skull base intra-extracranial extension meningioma].

Objective: To summarize the experience of endoscopic endonasal approach in the treatment of anterior skull base with intra-extracranial extension meningioma, and to analyze the perioperative quality of life of patients, and to discuss the safety and efficacy of the treatment. Methods: A total of 83 cases of anterior skull base with intra-extracranial extension meningioma admitted to Xuanwu Hospital, Capital Medical University from October 2007 to October 2019, who underwent endoscopic endonasal approach tumor resection, were retrospectively analyzed. The quality of life of the patients were evaluated by Anterior Skull Base Questionnaire (ASBQ) before and after surgery. The surgical techniques, extent of tumor resection, postoperative complications and the changes of patients' quality of life were summarized and analyzed. SPSS 23.0 software was used for statistical analysis. Results: A total of 57 anterior skull base with intra-extracranial extension meningioma patients were enrolled according to the inclusion and exclusion criteria, including 23 males and 34 females, aging (48.6±16.6) years. Fifty cases (87.7%) reached or exceeded Simpson gradeⅠ resection, and 7 cases underwent subtotal resection. Symptoms relief was as follows: headache relief in 45/50 (90%), vision improvement in 18/19 (94.7%), olfaction improvement in 6/45 (13.3%), mental symptoms improvement in 3/9 (33.3%), and seizure relief in 5/7 (71.4%). Postoperative complication included mental symptoms in 5 cases, cerebrospinal fluid leakage in 2 cases, epilepsy in 2 cases, frontal lobe hemorrhage in 1 case, and intracranial infection in 1 case. The follow-up period was 38 to 144 months. There were two cases recurring and no death. ASBQ assessment showed significant improvement in general condition, physical function, role function, mood disorder, pain, vision impairment, and sleep disturbance at 1 month postoperatively, with continued improvement thereafter, and reached stable at 6 months postoperatively. Conclusion: Endoscopic endonasal approach surgery is able to achieve safe and effective tumor resection for anterior skull base intra-extracranial extension meningioma, and the quality of life of patients can be improved steadily.

[Overexpression of NAT10 induced platinum drugs resistance in breast cancer cell].

Objective: To observe the platinum drugs resistance effect of N-acetyltransferase 10 (NAT10) overexpression in breast cancer cell line and elucidate the underlining mechanisms. Methods: The experiment was divided into wild-type (MCF-7 wild-type cells without any treatment) group, NAT10 overexpression group (H-NAT10 plasmid transfected into MCF-7 cells) and NAT10 knockdown group (SH-NAT10 plasmid transfected into MCF-7 cells). The invasion was detected by Transwell array, the interaction between NAT10 and PARP1 was detected by co-immunoprecipitation. The impact of NAT10 overexpression or knockdown on the acetylation level of PARP1 and its half-life was also determined. Immunostaining and IP array were used to detect the recruitment of DNA damage repair protein by acetylated PARP1. Flow cytometry was used to detect the cell apoptosis. Results: Transwell invasion assay showed that the number of cell invasion was 483.00±46.90 in the NAT10 overexpression group, 469.00±40.50 in the NAT10 knockdown group, and 445.00±35.50 in the MCF-7 wild-type cells, and the differences were not statistically significant (P>0.05). In the presence of 10 µmol/L oxaliplatin, the number of cell invasion was 502.00±45.60 in the NAT10 overexpression group and 105.00±20.50 in the NAT10 knockdown group, both statistically significant (P<0.05) compared with 219.00±31.50 in wild-type cells. In the presence of 10 µmol/L oxaliplatin, NAT10 overexpression enhanced the binding of PARP1 to NAT10 compared with wild-type cells, whereas the use of the NAT10 inhibitor Remodelin inhibited the mutual binding of the two. Overexpression of NAT10 induced PARP1 acetylation followed by increased PARP1 binding to XRCC1, and knockdown of NAT10 expression reduced PARP1 binding to XRCC1. Overexpression of NAT10 enhanced PARP1 binding to LIG3, while knockdown of NAT10 expression decreased PARP1 binding to LIG3. In 10 µmol/L oxaliplatin-treated cells, the γH2AX expression level was 0.38±0.02 in NAT10 overexpressing cells and 1.36±0.15 in NAT10 knockdown cells, both statistically significant (P<0.05) compared with 1.00±0.00 in wild-type cells. In 10 µmol/L oxaliplatin treated cells, the apoptosis rate was (6.54±0.68)% in the NAT10 overexpression group and (12.98±2.54)% in the NAT10 knockdown group, both of which were statistically significant (P<0.05) compared with (9.67±0.37)% in wild-type cells. Conclusion: NAT10 overexpression enhances the binding of NAT10 to PARP1 and promotes the acetylation of PARP1, which in turn prolongs the half-life of PARP1, thus enhancing PARP1 recruitment of DNA damage repair related proteins to the damage sites, promoting DNA damage repair and ultimately the survival of breast cancer cells.

Changes in the hepatitis B surface antibody in childhood acute lymphocytic leukaemia survivors after treatment with the CCLG-ALL 2008 protocol.

Antibody levels after hepatitis B virus (HBV) vaccination may be affected by suppression of the immune system due to cancer therapy. As such, childhood acute lymphocytic leukaemia (ALL) survivors are at risk of HBV infection due to immunosuppression secondary to chemotherapy. However, the hepatitis B surface antibody (HBsAb)-seropositive rate of childhood ALL survivors after chemotherapy is unknown, and the need to revaccinate HBsAb-seronegative ALL survivors is not appreciated in China. To assess the changes in HBsAb before and after chemotherapy, we retrospectively analyzed clinical data from 547 patients treated with the Chinese Children Leukaemia Group (CCLG)-ALL 2008 protocol from 1 April 2008 to 30 August 2019. The results revealed that 416 patients (76·1%) were HBsAb-seropositive at diagnosis, and at the time of the cessation of chemotherapy, 177 patients (32·4%) were HBsAb-seropositive and 370 patients (67·6%) were HBsAb-seronegative. Interestingly, 11 patients who were HBsAb-seronegative at diagnosis converted to seropositive at the time of the cessation of chemotherapy. HBsAb titres were decreased after chemotherapy (P < 0·0001). Further, patients with higher HBsAb titres at diagnosis were more likely to maintain protective antibody titres at the completion of chemotherapy (P < 0·0001). The loss of antibody was more remarkable in younger patients (≤ 10 years) both at diagnosis (P = 0·009) and at the completion of chemotherapy (P = 0·006). In summary, this study showed that 67·6% of patients were HBsAb-seronegative at the time of the cessation of chemotherapy, which indicates that ALL survivors are at high risk of HBV. As a result, HBV revaccination after chemotherapy should be highly valued in ALL survivors.

[Endovascular recanalization of symptomatic non-acute intracranial arterial occlusion: a single center case series].

Objective: To investigate the feasibility and safety of endovascular recanalization for symptomatic non-acute intracranial arterial occlusion (NAICO). Methods: Twenty-five consecutive patients who underwent endovascular recanalization for NAICO between January 2017 and October 2019 at Department of Neurosurgery, Beijing Hospital were retrospectively reviewed.There were 20 males and 5 females, aged (60.5±11.0) years (range: 41 to 73 years).The preoperative modified Rankin score(M(Q(R))) was 2 (2.5)(range: 1 to 5).The occlusion time was 40 (54)days (range: 17 to 570 days).The demographic data were collected. The initial procedural results, including the rate of successful recanalization, periprocedural complications and data pertaining to angiographic and clinical follow-up were recorded. Results: Recanalization was successful in 20 of 27 occlusive lesions of 25 patients. Intraoperative complications occurred in 3 cases, including vascular perforation in 1 case, arterial dissection in 1 case, and perforator occlusion occurred in 1 case. The incidence of permanent complications was 3.7% (1/27). All 25 patients underwent clinical follow-up, with a median period of 8 months (range: 1 to 33 months), and 23 patients with improved or stable modified Rankin scale. One patient developed new ischemic symptoms 2 months after discharge, and 1 patient died of complications of bed rest.The results of the angiography follow-up (median 4 months, range: 2 days to 9 months) showed that reocclusion occurred in 5 of all 20 successfully recanalized patients. Conclusions: Endovascular recanalization for symptomatic NAICO is feasible, relatively safe, and efficacious in highly selected cases. However, further larger scale pilot studies are needed to determine the efficacy and long-term outcome associated with this treatment.

[Preliminary application of drug-coated balloon in patients with symptomatic intracranial vertebrobasilar artery stenosis].

Objective: To explore the safety and short-term efficacy of drug-coated balloon (DCB) angioplasty for patients with symptomatic intracranial vertebrobasilar artery stenosis. Methods: Sixteen patients with symptomatic intracranial vertebrobasilar artery stenosis who received DCB angioplasty from September 2018 to December 2019 at Department of Neurosurgery, Beijing Hospital were retrospectively reviewed. There were 15 males and 1 female, aged (63.1±9.2) years (range: 48 to 77 years). Patients' demographics, lesions characteristics, complications, clinical and imaging follow-up data were collected and analyzed. Results: A total of 19 symptomatic intracranial vertebrobasilar artery stenosis were successfully treated with DCB.The degree of stenosis of lesion was 75% (20%) (M(Q(R))) before operation and 0 (20%) after operation. One posterior circulation stroke due to perforator artery occlusion happened in peri-procedural period.With a mean imaging follow-up time of 5.5 months, there was no restenosis occurred. Within a mean clinical follow-up period of 6.3 months, no new symptoms happened. Conclusion: For patients with symptomatic intracranial vertebrobasilar artery stenosis, DCB angioplasty seems relatively high safety with satisfactory short-term clinical and imaging outcomes.

Aclidinium bromide inhibits human glioma cell proliferation, migration and invasion and promotes apoptosis via the PI3K/AKT signaling pathway.

This study investigates the anti-cancer potential of Aclidinium bromide (INN) in glioblastoma. Glioblastoma cell lines U251 and U87 were treated with INN and its effects on cell migration and invasion were assessed by transwell migration and invasion assays., The effects of INN on proliferation and apoptosis were detected by CCK-8 kit and flow cytometry, and Western blotting determined anti-apoptotic proteins and signaling pathway changes. The results show that INN effectively suppressed proliferation, migration and invasion and induced apoptosis in U251 and U87 cells, respectively. Furthermore, the expression levels of the Bcl-2 anti-apoptotic protein was significantly decreased while Bax and caspase-3 expression were both increased in glioblastoma cells (all, p<0.05). Moreover, INN inactivated the PI3K/AKT signaling pathway by down-regulating the level of p-AKT, p-mTOR, P70 and CyclinD1 (all, p<0.05). In conclusion, our data suggests that INN could provide novel anticancer therapy in the treatment of glioblastoma.

[Sole angioplasty with tiny balloon for high-risk complex symptomatic intracranial atherosclerotic stenosis].

Objective: To explore the safety and short-term efficacy of sole angioplasty with tiny balloon for symptomatic intracranial atherosclerotic stenosis (ICAS) patients with complex lesions refractory. Methods: Consecutive 11 patients with complex ICAS lesions treated by sole angioplasty with tiny balloon (diameter≤2 mm) from September 2016 to November 2017 at Department of Neurosurgery, Beijing Hospital were retrospectively reviewed. Patients' demographics, lesions characteristics, procedures, complications, and clinical and imaging follow-up data were collected. There were 6 male and 5 female patients with mean age of 63.6 years (range: 45 to 77 years). Clinical manifestations were transient ischemia attack (TIA) in 4 cases, progressive ischemic stroke in 3 cases, recurrent stroke in 3 cases, and 1 case for preparation of scheduled radical resection of colon cancer. ICAS locations were middle cerebral artery M1 segment in 5 cases, M2 segment in 1 case, anterior cerebral artery A1 segment in 2 cases, and intracranial vertebral artery in 3 cases. Mean degree of ICAS stenosis was 92%. Lesion morphology was type A in 3 cases, B in 4 cases and C in 4 cases by Mori classification. Forward flow by modified thrombolysis in cerebral infarction (mTICI) was grade 1 to 2a in 8 cases, 2b in 3 cases. Collateral compensation grading was grade 2 in 5 cases, grade 3 in 6 cases. Results: Technique success rate was 10/11, peri-procedural complication rate was 1/11. Post-procedural forward flow in all cases had been enhanced and 10 cases obtained mTICI 2b to 3. Ten patients got favorable outcomes (modified Rankin score 0 to 2) at discharge. With a mean clinical follow-up time of 5.4 months, 1 patient was found to have TIA recurrence. With a mean clinical follow-up time of 7.4 months, 1 patient was found to have TIA recurrence. Eight in 11 cases obtained imaging follow-up during 3 months, and none restenosis was found. Conclusion: For symptomatic ICAS complex lesions, sole angioplasty with tiny balloon demonstrates relatively high safety with satisfactory short-term clinical and imaging results.

[Study of correlation between carotid artery tortuosity and atherosclerotic carotid artery stenosis].

Objective: To investigate the correlation between carotid artery tortuosity and atherosclerotic carotid artery stenosis. Methods: A total of 73 patients who underwent carotid computed tomography angiography with unilateral atherosclerotic carotid artery stenosis at Department of Neurosurgery of Beijing Hospital from January 2011 to June 2016 were retrospectively reviewed. There were 51 males and 22 females ranging from 48 to 90 years old, the average age was (65.9±9.5) years. There were 38 patients with carotid stenosis in the left carotid artery and 35 in the right, the stenosis degree of carotid artery ranged from 30% to 90% with the median was 44.0% (25.5%). According to the degree of carotid artery stenosis, the patients were classified into mild stenosis group and moderate/severe stenosis group. There were 43 patients in the mild stenosis group with an average stenosis degree of (37.5±5.4)%, there were 30 patients in moderate/severe stenosis group with an average stenosis degree of (65.6±10.9)%. The carotid artery (CCA) tortuosity, extracranial internal carotid artery (EICA) tortuosity and CCA-ICA bifurcation tortuosity were quantified by measuring the CCA tortuosity index, EICA tortuosity index and the internal carotid artery (ICA) angle, respectively. Comparison of diseased and normal carotid arteries was performed using t test or Wilcoxon signed-ranked test. Results: There were no statistically significant differences in CCA tortuosity index (Z=-0.584, P=0.559), ICA angle (t=0.278, P=0.781), and EICA tortuosity index (Z=-0.377, P=0.706) between diseased and normal carotid arteries in 73 patients. The diseased carotid arteries showed larger ICA angles (39.0° (19.0°) vs. 30.0° (15.0°)) (Z=-2.439, P=0.015) in the mild stenosis group, but smaller ICA angles ((31.5±11.7)° vs. (39.1±16.2)°) (t=-2.529, P=0.017) in the moderate/severe stenosis group, compared with the contralateral normal carotid arteries. There was no statistically significant difference in CCA (Z=-0.720, P=0.472; Z=-0.013, P=0.990) and EICA tortuosity index (Z=-0.349, P=0.727; Z=-0.114, P=0.909) between diseased and normal carotid arteries. Conclusions: Compared with normal carotid arteries, carotid arteries with mild atherosclerotic stenosis demonstrate a more tortuous CCA-ICA bifurcation, while those with moderate/severe stenosis demonstrate a straighter CCA-ICA bifurcation. There is no correlation between CCA, EICA tortuosity and carotid artery stenosis.

Correlation of preoperative ROMA scores with clinical stage in epithelial ovarian cancer patients.

PURPOSE: The significance of the Risk of Ovarian Malignancy Algorithm (ROMA) in differentiating benign and malignant ovarian lesions has been evidenced. In our clinical work, we found that advanced ovarian cancer were accompanied commonly with high ROMA scores. Thus, this study aimed to clarify the performance of ROMA in different disease stage of epithelial ovarian cancer (EOC) prior to surgery. METHODS: Carbohydrate antigen (CA125) and human epididymis protein 4 (HE4) levels and ROMA scores in 221 patients with FIGO stage I, II or III/IV stage EOC were analyzed. The positive rates of CA125, HE4 and ROMA at each disease stage were calculated. Their cutoff values, sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for distinguishing patients with FIGO stage I/II from those with FIGO stage III/IV were estimated via ROC curves. RESULTS: Serum CA125 and HE4 levels and ROMA scores rose significantly with advancing stage. ROMA and CA125 were significantly elevated more frequently in comparing with HE4 in EOC patients at with the same stage. Based on ROC curves, the cutoff values for FIGO stage III/IV EOC were 110 IU/mL, 126 pmol/L, 78 and 68% for CA125, HE4, premenopausal and postmenopausal ROMA, respectively. ROMA was the strongest predictor of FIGO stage, with the highest specificity, accuracy, and PPV, which were 84.4, 82.5, and 87.0% for postmenopausal patients, 89.3, 85.6, and 74.3% for premenopausal patients. CONCLUSIONS: Our data suggest high ROMA scores correlated with advanced ovarian cancer prior to surgery. These observations suggest potential utility of ROMA in the comprehensively preoperative evaluation of EOC patients.

Multiple energy synchrotron biomedical imaging system.

A multiple energy imaging system that can extract multiple endogenous or induced contrast materials as well as water and bone images would be ideal for imaging of biological subjects. The continuous spectrum available from synchrotron light facilities provides a nearly perfect source for multiple energy x-ray imaging. A novel multiple energy x-ray imaging system, which prepares a horizontally focused polychromatic x-ray beam, has been developed at the BioMedical Imaging and Therapy bend magnet beamline at the Canadian Light Source. The imaging system is made up of a cylindrically bent Laue single silicon (5,1,1) crystal monochromator, scanning and positioning stages for the subjects, flat panel (area) detector, and a data acquisition and control system. Depending on the crystal's bent radius, reflection type, and the horizontal beam width of the filtered synchrotron radiation (20-50 keV) used, the size and spectral energy range of the focused beam prepared varied. For example, with a bent radius of 95 cm, a (1,1,1) type reflection and a 50 mm wide beam, a 0.5 mm wide focused beam of spectral energy range 27 keV-43 keV was obtained. This spectral energy range covers the K-edges of iodine (33.17 keV), xenon (34.56 keV), cesium (35.99 keV), and barium (37.44 keV); some of these elements are used as biomedical and clinical contrast agents. Using the developed imaging system, a test subject composed of iodine, xenon, cesium, and barium along with water and bone were imaged and their projected concentrations successfully extracted. The estimated dose rate to test subjects imaged at a ring current of 200 mA is 8.7 mGy s-1, corresponding to a cumulative dose of 1.3 Gy and a dose of 26.1 mGy per image. Potential biomedical applications of the imaging system will include projection imaging that requires any of the extracted elements as a contrast agent and multi-contrast K-edge imaging.

Mechanism of serum miR-21 in the pathogenesis of familial and triple negative breast cancer.

The aim of this study was to clarify the mechanism of miR-21 in familial and triple-negative breast cancer (TNBC) by exploring the expression of serum miR-21. The sera were collected from healthy women at high risk of breast cancer. miR-39 was employed as the external reference, and real-time fluorescence quantitative PCR was used to detect the expression of serum miR-21 in 77 subjects. The miR-21 expression of the familial breast cancer group, TNBC group, and breast cancer high risk group were significantly higher than those in the normal control group and other breast cancer groups (P less than 0.01). A high serum miR-21 expression level was associated with lymph node metastasis and Ki67 expression (P less than 0.01). Serum miR-21 was closely associated with TNBC and familial breast cancer, and its expression was associated with genetic expression, degree of malignancy, and prognosis.

Prognostic significance of Versican expression in gastric adenocarcinoma.

Gastric cancer (GC) is the leading malignancy in the digestive system. Versican is a ubiquitous component of the extracellular matrix and has a role in tumor progression. We aim to examine the expression of Versican in GC and the relationship between Versican levels and patient survival. We detected the mRNA expression of Versican in tumorous pairs and adjacent normal tissues (ANTs) of 78 GC patients by quantitative real-time polymerase chain reaction. The protein expression of Versican in 101 cases of matched GC and ANT, as well as in 27 intraepithelial neoplastic (IN) samples, was evaluated by immunohistochemistry. We analyzed the correlation between Versican levels and clinical outcomes. Finally, we performed CCK-8 cell counting assay and transwell assay in GC cell lines. Versican mRNA expression was significantly greater in tumor tissues (P<0.001) than in ANT. Versican was majorly expressed in the stroma surrounding tumor epithelium and minorly some areas of tumor epithelium. The Versican expression level was higher in GC than in ANT (P=0.004), but no significant difference was observed between ANT and IN (P=0.517). The Versican mRNA and protein levels were consistent in GC. High Versican mRNA and protein expression correlated with greater tumor invasion depth (P=0.030, P=0.027). Univariate and multivariate analysis revealed that patients with high Versican mRNA expression exhibited poor disease-specific survival (P<0.001). In vitro experiments showed that Versican overexpression promoted cell proliferation and invasion. Our data indicate that Versican may be a novel prognostic indicator in GC and may be a potential target for clinical diagnosis.

Associations of miRNA polymorphisms and expression levels with breast cancer risk in the Chinese population.

Single-nucleotide polymorphisms in microRNAs (miRNAs) may dramatically affect gene expression and subsequently alter individual susceptibility to cancer, and thus has become a research hotspot for many cancer types, including breast cancer. We recruited 321 breast cancer patients and 290 controls in our study. Four established miRNA single-nucleotide polymorphisms (mir-499 rs3746444 A>G; miR-27a rs895819 A>G; miR-196a2 rs11614913 T>C; miR-146a rs2910164 G/C) were detected using Taqman assays. Mature miRNA expression, allele distribution, and the association with clinical features were further analyzed. Our results showed that the miR146a rs2910164 G/C polymorphism was associated with an elevated risk of breast cancer (odds ratio = 1.85, 95% confidence interval = 1.03-3.32; P < 0.05). Compared with the ancestral T allele in miR-196a2 rs11614913, the variant C allele was consistently associated with an increased risk of breast cancer (odds ratio = 2.20, 95% confidence interval = 1.19-4.09, P < 0.01) and clinical pathological type (P < 0.01). miR-27a rs895819 A>G and miR-499 rs3746444 A>G were not associated with breast cancer risk. Analysis of mature miRNA expression confirmed that the variant C allele in miR146a rs2910164 and miR-196a2 rs11614913 dramatically inhibited production of their mature products. Our results suggested that miR-146a rs2910164 G>C and miR-196a2 rs11614913 T>C may be biomarkers for predicting breast cancer risk in the Chinese population.

African-American men with low-grade prostate cancer have higher tumor burdens: results from the Duke Prostate Center.

BACKGROUND: To investigate racial differences in tumor burden (cancer volume, cancer percentage and cancer to PSA ratios) in a large cohort of men undergoing radical prostatectomy (RP). METHODS: Demographic, clinical and pathological data of patients undergoing RP between 1993-2010 were reviewed and compared between African-American (AA) and non African-American (nAA) men. Further assessments of pathological tumor burden (estimated tumor volume, percent of cancer involvement, and estimated tumor volume/PSA ratios) were performed across Gleason score categories. RESULTS: Of 4157 patients in the analysis, 604 (14.5%) were AA. Overall, AA patients were younger, had higher Gleason scores, PSA levels and incidence of palpable disease (all P < 0.001). Despite comparable prostate weights (39.4 vs. 39.6 g), AA men had higher percent cancer involvement and estimated tumor volume (all P < 0.001) but similar estimated tumor volume/PSA ratios ( P> 0.05). When stratified by Gleason scores, prostate weights were comparable; however, estimated tumor volume, percent cancer involvement and estimated tumor volume/PSA ratios were higher in AA men with low grade (≤ 6) prostate cancer (PCa), similar in intermediate grade (7-8) and lower in high grade (9-10) PCa compared to nAA men. CONCLUSIONS: In this large series, AA patients had higher disease burden (estimated tumor volume, percent cancer involvement, estimated tumor volume/PSA ratios) compared to nAA but this association was especially pronounced in low grade (Gleason ≤ 6) cancers. These data depict a complex picture of relations between race and tumor burden across the spectrum of PCa aggressiveness. Further investigation is warranted to understand the mechanisms of racial disparities in PCa.

SU-E-T-578: Beam Energy Dependence and Intermediate-Low Dose Bath on Normal Tissue When Comparing VMAT with Conventional IMRT.

PURPOSE: To evaluate the impact of beam energy and intermediate-low dose bath on normal tissue when comparing volumetric modulated arc therapy (VMAT) with conventional IMRT. METHODS: A total of 10 prostate patients were randomly chosen for this study. The clinical IMRT plans were designed with 5 coplanar 10 MV photon beams. To investigate impacts of energies and delivery methods, we created 2 additional IMRT plans with 6 and 15 MV photons and 3 VMAT plans with 6, 10, and 15 MV photons in the Pinnacle treatment planning system. All plans were evaluated in terms of target coverage, clinical endpoints for organs-at-risks (OAR), and intermediate-low dose distributions to normal tissue, for which endpoints of V5Gy, V10Gy, V20Gy, V30Gy, V40Gy, and V50Gy were used. For this study, normal tissue was further divided into near region (5 cm thick concentric shell of normal tissue surrounding the target) and far region (concentric shell of normal tissue surrounding the near region and target). Longitudinally, the total normal tissue in calculation was limited to 10 cm from field edges. RESULTS: No significant differences were found among 6 types of treatment plans in terms of target coverage, OAR sparing, plan quality, intermediate-low doses to the near region, and integral dose to the total normal tissue (p > 0.05). VMAT deposited less intermediate doses of 30-50 Gy and more low doses of 5-10 Gy to the far region than IMRT. For example, mean average V40Gy and V10Gy were 51 and 2,967 cc for VMAT, and 140 and 2,618 cc for IMRT, respectively. CONCLUSIONS: VMAT and IMRT plans created with different photon energies are comparable for target coverage and OAR sparing. For prostate treatment, VMAT redistribute normal tissue doses from intermediate range into low dose range while keeping the similar the integral dose as IMRT.

SU-E-T-486: Volume and Location Dependence on the Difference Between Monte Carlo and Pencil Beam Dose Calculations for Lung Stereotactic Body Radiation Therapy.

PURPOSE: Stereotactic body radiotherapy has been an efficacious treatment modality for early stage non-small cell lung cancer. The accuracy of dose calculations is in question due to the presence of inhomogeneity. It was required in several clinical trials to calculate dose without heterogeneity correction. However, to better correlate the outcomes with the planned dose, accurate dose calculation with heterogeneity correction is highly desirable. METHODS: We compared the recalculated dose with Monte Carlo (MC) algorithm to the original Pencil Beam (PB) calculations for clinical lung SBRT plans. Thirty-one clinical plans that followed protocol guidelines were retrospectively investigated. Dosimetric parameters D1, D95 and D99 for the PTV and D1 for organs at risk were compared. Correlations of mean lung dose and V20 of lungs between two calculations were investigated. RESULTS: Compared to the PB calculations without heterogeneity correction in clinical plans, we found that in terms of D95 of PTV, (1) the two calculations resulted in similar D95 for edge tumors with volumes greater than 25.1cc; (2) an average overestimation of 5% in PB calculations for edge tumors with volumes less than 25.1cc; and (3) an average overestimation of 9% or underestimation of 3% in PB calculations for island tumors with volumes smaller or greater than 22.6 cc, respectively. With heterogeneity correction, the PB calculation resulted in an average reduction of 23.8% and 15.3% in D95 for island and edge lesions respectively compared to the MC calculation. For organs at risks, no clinical meaningful differences were found among all the comparisons. Excellent correlations for mean dose and V20 of lungs were observed between the two calculations. CONCLUSIONS: Using a single scaling factor to account for the differences in using heterogeneity correction may not be sufficient. To understand dose-response relation in Lung SBRT, accurate dose calculation such as the Monte Carlo algorithms is highly recommended.

SU-E-J-22: Effect of MLC Leaf Width on MLC Leaf Shifting Algorithm for Concurrent Treatment of Prostate and Pelvic Lymph Nodes.

PURPOSE: Our previous study showed that adjusting selected MLC leaf pairsto follow prostate movement is an effective strategy to account for daily prostate displacement during concurrent treatment with pelvic lymph nodes. MLC leaf width affects the quality of MLC shifting plans for longitudinal prostate motion compensation. This study is to investigate the effect of the MLC leaf width in compensation of the prostate movement. METHODS: Fifty-one daily CT on-rail scans from three patients were available for this study. On these CTs, the prostate, bladder and rectum were manually contoured, and the lymph nodes contours were transferred from the planning CT after rigid bony registration. For each patient, three different IMRT plans were created based on a planning CT using leaf width of 2.5, 5, and 10 mm, respectively. For each CT, the prostate displacement was determined by dual imaging registration and compensated by shifting MLC resulting in a total of 153 MLC shifted plans. RESULTS: Among 51 daily CTs, the average prostate movement along the superior/inferior direction was 1.1±3.7 mm (range: -6 to 6.5 mm). The differences in D99 of the prostate between the dose of the day and dose of the plan were 2.3±3.3%, 1.3±2.0%, and 4.4±5.1% for 2.5, 5, and 10 mm leaf width plans, respectively (p<<0.05). The corresponding differences in D99 of the lymph nodes were 0.7±0.9%, 0.6±0.9%, and 1.4±0.8%. The mean differences in D50 were 0.8%, 1.6%, and 2.7% for the bladder, and 10.0%, 3.9%, and 5.7% for the rectum, respectively. CONCLUSIONS: Using the MLC Shifting method to compensate for prostate movement in the longitudinal direction depends on the MLC leaf width and the magnitude of the prostate motion. The use of leaf width of 5 mm can provide sufficient tumor coverage without significantly affecting doses to the critical structures.