Search

Colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer-related mortality worldwide. Even with advances in therapy, CRC mortality remains high. Therefore, there is an urgent need to develop effective therapeutics for CRC. PCTAIRE protein kinase 1 (PCTK1) is an atypical member of the cyclin-dependent kinase (CDK) family, and the function of PCTK1 in CRC is poorly understood. In this study, we found that patients with elevated PCTK1 levels had a better overall survival rate in CRC based on the TCGA dataset. Functional analysis also showed that PCTK1 suppressed cancer stemness and cell proliferation by using PCTK1 knockdown (PCTK1-KD) or knockout (PCTK1-KO) and PCTK1 overexpression (PCTK1-over) CRC cell lines. Furthermore, overexpression of PCTK1 decreased xenograft tumor growth and knockout of PCTK1 significantly increased in vivo tumor growth. Moreover, knockout of PCTK1 was observed to increase the resistance of CRC cells to both irinotecan (CPT-11) alone and in combination with 5-fluorouracil (5-FU). Additionally, the fold change of the anti-apoptotic molecules (Bcl-2 and Bcl-xL) and the proapoptotic molecules (Bax, c-PARP, p53, and c-caspase3) was reflected in the chemoresistance of PCTK1-KO CRC cells. PCTK1 signaling in the regulation of cancer progression and chemoresponse was analyzed using RNA sequencing and gene set enrichment analysis (GSEA). Furthermore, PCTK1 and Bone Morphogenetic Protein Receptor Type 1B (BMPR1B) in CRC tumors were negatively correlated in CRC patients from the Timer2.0 and cBioPortal database. We also found that BMPR1B was negatively correlated with PCTK1 in CRC cells, and BMPR1B expression was upregulated in PCTK1-KO cells and xenograft tumor tissues. Finally, BMPR1B-KD partially reversed cell proliferation, cancer stemness, and chemoresistance in PCTK1-KO cells. Moreover, the nuclear translocation of Smad1/5/8, a downstream molecule of BMPR1B, was increased in PCTK1-KO cells. Pharmacological inhibition of Smad1/5/8 also suppressed the malignant progression of CRC. Taken together, our results indicated that PCTK1 suppresses proliferation and cancer stemness and increases the chemoresponse of CRC through the BMPR1B–Smad1/5/8 signaling pathway.

The incidence of colorectal cancer (CRC) has increased significantly in the past decade. Early diagnosis and new therapeutics are still urgently needed for CRC in clinical practice. Human α-defensin 6 (HD6) plays a defense role against microbes in the gastrointestinal tract. However, the role and mechanism of HD6 in CRC is still unresolved. Specimens from CRC patients with higher HD6 showed better outcomes. Overexpressed HD6 in CRC cells caused a reduction of cell proliferative, migratory, and invasive ability in vitro and in vivo. HD6-overexpressed caused S phase arrest through changes in cyclin-A and B and CDK2 levels. In addition, serpine-1 may be negatively regulated by HD6 altering the translocation of c-Jun N-terminal kinases (JNK), extracellular regulated protein kinases (ERK), and p38. Higher HD6 and lower serpine-1 levels in CRC patients reflected better outcomes. Finally, we found that HD6 interacts directly with epidermal growth factor receptor (EGFR) by co-immunoprecipitated assay. EGF treatment caused an increase of the level of serpine-1 and pEGFR levels and then increased growth activity in HD6 overexpressing cells. Together, our study shows that HD6 may compete with EGF to bind to EGFR and interrupt cancer progression in CRC. We believe these findings may give new insights for HD6 in CRC therapy.

Malignant glioma can be divided into grade III (Gr. III) and grade IV (Gr. IV). Gr. III glioma patients have significantly better overall survival (OS) than those with Gr. IV glioma, also known as glioblastoma multiforme (GBM). We explored differentially expressed genes (DEGs) from the GSE4290 and GSE109857 datasets between Gr. III and Gr. IV gliomas. Six candidate prognostic genes for GBM were determined from survival analysis of data obtained from The Cancer Genome Atlas (TCGA), and the results were validated via assessments of the OS of Gr. III glioma and GBM patients using data obtained from the Chinese Glioma Genome Atlas (CGGA). Then, the expression levels of CXCL8, also named IL8, had a significant relationship with progression-free survival (PFS) in Gr. IV patients (P = 0.028), and had no effect in Gr. III glioma patients (P = 0.522). Furthermore, the receiver operating characteristic (ROC) curve revealed the critical role of IL8 with an accuracy value of 0.899 for discriminating Gr. IV from Gr. III in TCGA and 0.644 in CGGA. Macrophage (P

Glioblastoma multiforme (GBM) is a deadly malignant brain tumor that is resistant to most clinical treatments. Novel therapeutic agents that are effective against GBM are required. Antrodia cinnamomea has shown antiproliferative effects in GBM cells. However, the exact mechanisms and bioactive components remain unclear. Thus, the present study aimed to investigate the effect and mechanism of 4-acetylantrocamol LT3 (4AALT3), a new ubiquinone from Antrodia cinnamomeamycelium, in vitro. U87 and U251 cell lines were treated with the indicated concentration of 4AALT3. Cell viability, cell colony-forming ability, migration, and the expression of proteins in well-known signaling pathways involved in the malignant properties of glioblastoma were then analyzed by CCK-8, colony formation, wound healing, and western blotting assays, respectively. We found that 4AALT3 significantly decreased cell viability, colony formation, and cell migration in both in vitro models. The epidermal growth factor receptor (EGFR), phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR), Hippo/yes-associated protein (YAP), and cAMP-response element binding protein (CREB) pathways were suppressed by 4AALT3. Moreover, 4AALT3 decreased the level of DNA repair enzyme O6-methylguanine-DNA methyltransferase and showed a synergistic effect with temozolomide. Our findings provide the basis for exploring the beneficial effect of 4AALT3 on GBM in vivo.

Primary brain malignancy is a rare tumor with a global incidence of less than 10 per 100,000 people. Hence, there is limited power for identifying risk loci in individual studies, especially for Han Chinese. We performed a genome-wide association study (GWAS) in Taiwan, including 195 cases and 195 controls. We identified five new genes for malignant neoplasms of the brain: EDARADD (rs645507, 1p31.3, p = 7.71 × 10−5, odds ratio (OR) = 1.893), RBFOX1 (rs8044700, p = 2.35 × 10−5, OR = 2.36), LMF1 (rs3751667, p = 7.24 × 10−7, OR = 2.17), DPP6 (rs67433368, p = 8.32 × 10−5, OR = 3.94), and NDUFB9 (rs7827791, p = 9.73 × 10−6, OR = 4.42). These data support that genetic susceptibility toward GBM or non-GBM tumors is highly distinct, likely reflecting different etiologies. Combined with signaling analysis, we found that RNA modification may be related to major risk factors in primary malignant neoplasms of the brain.

Background: Radiotherapy (RT) provides a modern treatment to enhance the malignant glioma control rate. The purpose of our study was to determine the effect of tumor coverage on disease prognosis and to predict optimal RT plans to achieve a lower normal tissue complication probability (NTCP). Methods: Ten malignant-glioma patients with tumors adjacent to organs at risk (OARs) were collected. The patients were divided into two groups according to adequate coverage or not, and prognosis was analyzed. Then, using intensity-modulated radiation therapy (IMRT), volume-modulated arc therapy (VMAT), and helical tomotherapy (TOMO) to simulate new treatment plans for 10 patients, the advantages of these planning systems were revealed for subsequent prediction of NTCP. Results: The results of clinical analysis indicated that overall survival (p = 0.078) between the adequate and inadequate groups showed no differences, while the adequate group had better recurrence-free survival (p = 0.018) and progression-free survival (p = 0.009). TOMO had better CI (p < 0.001) and also predicted a lower total-irradiated dose to the normal brain (p = 0.001) and a lower NTCP (p = 0.027). Conclusions: The TOMO system provided optimal therapeutic planning, reducing NTCP and achieving better coverage. Combined with the clinical results, our findings suggest that TOMO can make malignant glioma patients close to OARs achieve better disease control.

Whole-brain radiotherapy (WBRT) is commonly used in patients with multiple brain metastases. Compared with conventional WBRT, hippocampal avoidance WBRT (HA-WBRT) more favorably preserves cognitive function and the quality of life. The hippocampal volume is considerably small (approximately 3.3 cmWe included 18 patients with brain metastasis. All target and avoidance structures were contoured by an experienced radiation oncologist. The prescribed dose was 30 Gy in 10 fractions. For each patient, three different treatment plans were generated for comparison: VMAT with couch-shift, VMAT without couch-shift, and TomoTherapy. All treatment plans fulfilled Radiation Therapy Oncology Group (RTOG) 0933 criteria for HA-WBRT. The Wilcoxon paired signed-rank test was used to compare different treatment plans.VMAT with couch-shift had the better average conformity index (0.823) with statistically significant difference compared to VMAT without couch-shift (0.810). VMAT with couch-shift (0.219) had a more favorable average homogeneity index (HI) than did VMAT without couch-shift (0.230), although the difference was not significant. TomoTherapy had an optimal average HI of 0.070. In terms of the hippocampus, all three treatment plans met the RTOG 0933 criteria. VMAT with couch-shift had a lower average DThe plan quality of VMAT for HA-WBRT was improved by using the couch-shift technique to simulate the half MLC leaf width. However, the improvement was not statistically significant except conformity index. The downsizing effect decreased with the use of the sophisticated grade of VMAT. TomoTherapy offered superior plan quality but required the longest delivery time.

Neurosurgeons require considerable expertise and practical experience to deal with the critical situations commonly encountered in complex surgical operations such as cerebral cancer; however, trainees in neurosurgery seldom have the opportunity to develop these skills in the operating room. Physical simulators can give trainees the experience they require. In this study, we adopted advanced molding and replication techniques in the fabrication of a physical simulator for use in practicing the removal of cerebral tumors. Our combination of additive manufacturing and molding technology with elastic material casting made it possible to create a simulator that realistically mimics the skull, brain stem, soft brain lobes, and cerebral cancer with cerebral tumors located precisely where they are likely to appear. Multiple and systematic experiments were conducted to prove that the elastic material used herein was appropriated for building professional medical physical simulator. One neurosurgical trainee reported that under the guidance of a senior neurosurgeon, the physical simulator helped to elucidate the overall process of cerebral cancer removal and provided a realistic impression of the tactile feelings involved in craniotomy. The trainee also learned how to make decisions when facing the infiltration of a cerebral tumor into normal brain lobes. Our results demonstrate the efficacy of the proposed physical simulator in preparing trainees for the rigors involved in performing highly delicate surgical operations.

We investigated the organ-sparing effect of the deep inspiration breath hold (DIBH) technique among different levels of lung expansion for left-side breast radiotherapy. This retrospective study enrolled 30 patients who received adjuvant left breast radiotherapy after breast-conserving surgery (BCS). Simulation scans of both DIBH and deep breathing four-dimensional computed tomography (4DCT) were acquired, and three treatment plans were generated for each patient. One plan was based on the DIBH images, and the other two plans were based on the mid-lung expansion (ME) and initial lung expansion (IE) phases retrieved from 4DCT data sets. Dosimetric comparisons and normal tissue complication probability (NTCP) models were conducted. We used image registration for displacement analysis and sought potential factors related to the dose benefit of DIBH. The DIBH plans resulted significantly lower doses to the heart, left ventricle (LV) and left anterior descending coronary artery (LAD), including the high- to low-dose areas, followed by the ME plans and IE plans (p < 0.05). DIBH reduced the risk of long-term cardiac mortality by 40% and radiation pneumonitis of the left lung by 37.96% compared with the IE plans (p < 0.001). The reduction in the mean dose to the heart and LV significantly correlated with anterior displacement of the left lung. The DIBH technique is a feasible tool to provide dosimetric and clinical advantages for adjuvant left-sided breast radiotherapy. Breathing pattern and the level of lung expansion seem to play an important role.

Hydrocephalus is a complication of spontaneous intracerebral hemorrhage; however, its predictive relationship with hydrocephalus in this patient cohort is not understood. Here, we evaluated the incidence and risk factors of hydrocephalus after craniectomy.Retrospectively studied data from 39 patients in the same hospital from 2016/01 to 2020/12 and analyzed risk factors for hydrocephalus. The clinical data recorded included patient age, sex, timing of surgery, initial Glasgow Coma Scale score, intracerebral hemorrhage (ICH) score, alcohol consumption, cigarette smoking, medical comorbidity, and blood data. Predictors of patient outcomes were determined using Student t test, chi-square test, and logistic regression.We recruited 39 patients with cerebral herniation who underwent craniectomy for spontaneous supratentorial hemorrhage. Persistent hydrocephalus was observed in 17 patients. The development of hydrocephalus was significantly associated with the timing of operation, cigarette smoking, and alcohol consumption according to the Student t test and chi-square test. Univariate and multivariate analyses suggested that postoperative hydrocephalus was significantly associated with the timing of surgery (P = .031) and cigarette smoking (P = .041).The incidence of hydrocephalus in patients who underwent delayed operation (more than 4 hours) was lower than that in patients who underwent an operation after less than 4 hours. nonsmoking groups also have lower incidence of hydrocephalus. Among patients who suffered from spontaneous supratentorial hemorrhage and need to receive emergent craniectomy, physicians should be reminded that postoperative hydrocephalus followed by ventriculoperitoneal shunting may be necessary in the future.

Glioblastoma multiforme (GBM) requires radiotherapy (RT) as its definitive management. However, GBM still has a high local recurrence rate even after RT. Cancer stem‐like cells (CSCs) might enable GBM to evade irradiation damage and cause therapeutic failure. The optimal RT plan should achieve a planning target volume (PTV) coverage of more than 95% but cannot always meet the requirements. Here, we demonstrate that irradiation with different tumor coverage rates to different brain areas has similar effects on GBM. To retrospectively analyze the relationship between PTV coverage and the survival rate in 26 malignant glioblastoma patients, we established primary cell lines from patient‐derived malignant glioblastoma cells with the PTV95 (PTV coverage of more than 95%) program (GBM‐MG1 cells) and the Non‐PTV95 (poor PTV coverage of less than 95%) program (GBM‐MG2 cells). The clinical results of PTV95 and Non‐PTV95 showed no difference in the overall survival (OS) rate (P = .390) between the two different levels of PTV coverage. GBM‐MG1 (PTV95 program) cells exhibited higher radioresistance than GBM‐MG2 (Non‐PTV95 program) cells. CD44 promotes radioresistance, CSC properties, angiogenesis and cell proliferation in GBM‐MG1 (PTV95 program) cells. GBM patients receiving RT with the PTV95 program exhibited higher radioresistance, CSC properties, angiogenesis and cell proliferation than GBM patients receiving RT with the Non‐PTV95 program. Moreover, CD44 plays a crucial role in these properties of GBM patients with the PTV95 program., Glioblastoma multiforme (GBM) patients receiving radiotherapy (RT) with the PTV95 program exhibited higher radioresistance, CSC properties, angiogenesis and cell proliferation than GBM patients receiving RT with the Non‐PTV95 program. Moreover, CD44 plays a crucial role in these properties of GBM patients with the PTV95 program.

Glioblastoma multiforme (GBM) is a deadly malignant brain tumor that is resistant to most clinical treatments. Novel therapeutic agents that are effective against GBM are required.

Neurosurgeons require considerable expertise and practical experience in dealing with the critical situations commonly encountered during difficult surgeries, however, neurosurgical trainees seldom have the opportunity to develop these skills in the operating room. Therefore, physical simulators are used to give trainees the experience they require. In this study, we created a physical simulator to assist in training neurosurgeons in aneurysm clipping and the handling of emergency situations during surgery. Our combination of additive manufacturing with molding technology, elastic material casting, and ultrasonication-assisted dissolution made it possible to create a simulator that realistically mimics the brain stem, soft brain lobes, cerebral arteries, and a hollow transparent Circle of Willis, in which the thickness of vascular walls can be controlled and aneurysms can be fabricated in locations where they are likely to appear. The proposed fabrication process also made it possible to limit the error in overall vascular wall thickness to just 2&ndash, 5%, while achieving a Young&rsquo, s Modulus closely matching the characteristics of blood vessels (~5%). One neurosurgical trainee reported that the physical simulator helped to elucidate the overall process of aneurysm clipping and provided a realistic impression of the tactile feelings involved in this delicate operation. The trainee also experienced shock and dismay at the appearance of leakage, which could not immediately be arrested using the clip. Overall, these results demonstrate the efficacy of the proposed physical simulator in preparing trainees for the rigors involved in performing highly delicate neurological surgical operations.

Introduction Glioblastoma multiforme (GBM) is the most common brain malignancy in adults, and currently available GBM treatments present several unique challenges. It is known that GBM involves cancer stem-like cells (CSCs) and tumor cells that aggressively invade normal brain tissues, and both cell types may cause resistance to radiotherapy (RT) and are thus responsible for therapeutic failure. The radioresistance of GBM cells relies on the efficient activation of the DNA damage response (DDR), but the mechanisms linking this response with stem-cell status and tumor invasion remain unclear. Materials and methods We used irradiation to treat patient-derived GBM (Par) cells and then purified radioresistant GBM (R2M2) cells through two rounds of irradiation and an invasion assay. Musashi-1 (MSI1) is a neural stem-cell marker and key oncogenic factor of GBM. We identified MSI1 expression to predict radioresistance through silencing an MSI1-high-expressing R2M2 cell line or inducing overexpression in a Par cell line with low/no MSI1 expression and assessing the subsequent DDR. Result MSI1 enhances tumor invasion via VCAM1 and modulates GBM radioresistance via the hyperactivation of the DDR through increasing homologous recombination repair and evading apoptosis. MSI1 knockdown induces DNA damage accumulation in irradiated GBM cells and promotes their depletion in vitro; MSI1 knockdown also inhibits the formation of GBMs generated by irradiated xeno-transplanted cells. MSI1 inhibition may radiosensitize tumors, prevent CSC-positive selection induced by RT, and reduce tumor invasion. Conclusion MSI1 may involve in regulating GBM radioresistance, invasion, and recurrence and could be a novel target for GBM treatment.

Purpose Hypofractionated radiotherapy can reduce treatment durations and produce effects identical to those of conventionally fractionated radiotherapy for treating prostate cancer. Volumetric arc radiotherapy (VMAT) can decrease the treatment machine monitor units (MUs). Previous studies have shown that VMAT with multileaf collimator (MLC) rotation exhibits better target dose distribution. Thus, VMAT with MLC rotation warrants further investigation. Methods and materials Ten patients with prostate cancer were included in this study. The prostate gland and seminal vesicle received 68.75 and 55 Gy, respectively, in 25 fractions. A dual-arc VMAT plan with a collimator angle of 0° was generated and the same constraints were used to reoptimize VMAT plans with different collimator angles. The conformity index (CI), homogeneity index (HI), gradient index (GI), normalized dose contrast (NDC), MU, and modulation complexity score (MCSV ) of the target were analyzed. The dose-volume histogram of the adjacent organs was analyzed. A Wilcoxon signed-rank test was used to compare different collimator angles. Results Optimum values of CI, HI, and MCSV were obtained with a collimator angle of 45°. The optimum values of GI, and NDC were observed with a collimator angle of 0°. In the rectum, the highest values of maximum dose and volume receiving 60 Gy (V60 Gy ) were obtained with a collimator angle of 0°, and the lowest value of mean dose (Dmean ) was obtained with a collimator angle of 45°. In the bladder, high values of Dmean were obtained with collimator angles of 75° and 90°. In the rectum and bladder, the values of V60 Gy obtained with the other tested angles were not significantly higher than those obtained with an angle of 0°. Conclusion This study found that MLC rotation affects VMAT plan complexity and dosimetric distribution. A collimator angle of 45° exhibited the optimal values of CI, HI, and MCSv among all the tested collimator angles. Late side effects of the rectum and bladder are associated with high-dose volumes by previous studies. MLC rotation did not have statistically significantly higher values of V60 Gy in the rectum and bladder than did the 0° angle. We thought a collimator angle of 45° was an optimal angle for the prostate VMAT treatment plan. The findings can serve as a guide for collimator angle selection in prostate hypofractionated VMAT planning.

// Jang-Chun Lin 1, 2, 3, 4 , Jo-Ting Tsai 1, 2 , Li-Jhen Chen 1 , Ming-Hsien Li 1 and Wei-Hsiu Liu 5, 6 1 Department of Radiation Oncology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan, ROC 2 Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC 3 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC 4 Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC 5 Department of Neurological Surgery, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan, ROC 6 Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC Correspondence to: Wei-Hsiu Liu, email: liubear0812bear@yahoo.com.tw Keywords: rectal cancer (RC), helical tomotherapy (TOMO), volumetric modulated arc therapy (VMAT), intensity modulated radiotherapy (IMRT), radiation dosimetry Received: October 21, 2016 Accepted: December 27, 2016 Published: January 31, 2017 ABSTRACT Objectives: To compare treatment plans for helical tomotherapy (TOMO), volumetric modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) for locally advanced rectal cancer (LARC). Materials and Methods: This retrospective study from December 2010 to June 2013 included 20 patients with LARC who received neoadjuvant concurrent chemoradiotherapy (CCRT) with radiation doses of greater than 50.4 Gy. Dosimetric quality was evaluated based on doses to organs at risk (OARs), including small bowel, urinary bladder and bilateral femoral head, over the same coverage of the clinical target volume (CTV). Results: In supine comparison of IMRT with VMAT, VMAT treatment plan had a lower hot spot dose (p=0.0154) and better conformity index (CI, p=0.0036) and homogeneity index (HI, p=0.0246). Lower bladder V34.98 (p=0.0008), V40 (p=0.0058), mean dose (p

To compare the effects of different photon energies on radiation planning by intensity-modulated radiotherapy (IMRT), volumetric-modulated arc therapy (VMAT) and helical tomotherapy (TOMO) for proximal gastric cancer (PGC). Network analysis with microarray procession and gene ontology were used to identify the effect of radiotherapy (RT) on PGC. Then, we retrospectively analyzed 8 PGC patients after receiving irradiation with a prescribed dose of 50.4 Gy. The Pinnacle treatment planning system (TPS, V9.8) was used to generate IMRT and VMAT plans by using 6 or 10 MV. TOMO plans were calculated on the Tomotherapy Planning Station Hi-Art Version 4.2.3 workstation (Tomotherapy Incorporated, Madison, WI, USA). PGC is associated with high DNA repair ability. TOMO plan results in higher tumor coverage and a better conformity index than IMRT and VMAT. 10-MV VMAT yields better dosimetric quality of the gradient index than 6-MV VMAT (P = .012). TOMO was associated with a lower irradiation dose in the mean dose to the right kidney (P = .049), left kidney and heart than 6-MV IMRT and 6-MV VMAT. 6-MV IMRT plan presented a higher dose of lung Dmean (P = .017) than 10-MV IMRT. Additionally, VMAT, using a planning energy of 6 MV, was associated with a significantly higher left kidney Dmean (P = .018) and V10 (P = .036) than a planning energy of 10 MV. TOMO is a better RT plan not only for tumor coverage but also for sparing organs at risk. IMRT and VMAT plans with 10 MV beams are more suitable than 6 MV beams for PGC treatment.

Glioblastoma multiforme (GBM) requires radiotherapy (RT) as a part of definitive management strategy. RT is highly effective, destroying cancer cells that may exist around the surgical tumor bed. However, GBM still has a poor prognosis and a high local recurrence rate after RT. Accumulating research indicates that GBM contains cancer stem-like cells (CSCs), which are radioresistant and result in therapeutic failure. Additionally, GBM cells can aggressively invade normal brain tissue, inducing therapeutic failure. Using clinical observations, we evaluated the effect of radiation on tumor control. We also explored the biomolecular pathways that connect radioresistance and CSC- and epithelial-mesenchymal transition (EMT)-associated phenotypes in patient-derived GBM cells. Transwell and microarray assay demonstrated that radioresistant GBM cells (GBM-R2I2) exhibit increased invasion and self-renewal abilities compared with parental GBM cells. Finally, to identify potential mechanisms underlying these observations, we used a PCR array to search for molecular markers of cell motility. Signal transducer and activator of transcription 3 (STAT3) directly bound to the Slug promoter in a chromatin immunoprecipitation assay. Reduced STAT3 decreased Slug expression and suppressed cell invasion in GBM-R2I2 cells while increasing Slug reversed these effects. In addition, STAT3 knockdown significantly inhibited CSC properties, synergistically increased the radiotherapeutic effect, and effectively increased the survival rate in vivo. We deciphered a new pathway of GBM radioresistance, invasion, and recurrence via the STAT3/Slug axis that could be a new target of GBM therapy.

To investigate the association between tumor response to thoracic radiotherapy and epidermal growth factor receptor (EGFR) mutation status in patients with lung adenocarcinoma, we collected 48 patients treated between January 2010 and December 2013. Of the 18 patients with EGFR mutation, 15 (83.3%) had a single mutation, and three (16.7%) had double mutation. Different EGFR mutation subtypes exhibited different responses to radiotherapy. The identified double EGFR mutations were associated with reduction of residual tumor burden (RTB) after radiotherapy. In univariate analysis, EGFR mutations in exon 18, 20, and 21 and double EGFR mutation were significant factors predicting RTB. In multivariate analysis, exon 20 mutation was the only significant factor. Patients with EGFR mutation seemed to have longer mean overall survival (OS) compared to the group with wild-type EGFR (31.1 vs. 26.6 months, p=0.49). The median and mean OS in patients with double EGFR mutation vs. wild-type EGFR were 20.1 vs. 16.9 months and 28.9 vs. 26.6 months, respectively. Further studies with larger sample size are warranted to clarify the association of EGFR mutation status with the lung tumor response after radiotherapy.

Objectives Survival in patients with locally advanced unresectable pancreatic cancer (LAUPC) is poor, and local recurrence continues to be a major problem in the management of this disease. Radiotherapy (RT) using different RT techniques, including intensity-modulated radiotherapy (IMRT) and stereotactic body radiation therapy (SBRT), may lead to different clinical outcomes for patients with LAUPC. Here, we compared SBRT with IMRT for patients with LAUPC with respect to survival rate, local control (LC) rate, and toxicity-related dose distribution. Materials and methods This retrospective study from March 2007 to March 2011 included 41 patients with LAUPC who were divided into two groups, with 20 patients receiving SBRT and 21 patients receiving IMRT. The median follow-up time was 16 months. Results For the IMRT and SBRT groups, the median survival times were 13 and 20 months, and 1-year overall survival (OS) rates were 70.7 and 80.0%, respectively. There was no difference in OS between the two RT techniques. RT with SBRT showed significantly better local disease-free survival than IMRT for patients with LAUPC. Tobacco use had a borderline effect on LC. Thus, further statistical analysis showed that patients who used tobacco had better LC after receiving SBRT than IMRT. Conclusion SBRT improved LC for LAUPC patients and had similar radiation toxicity compared with IMRT. Further study is required to define the effects of administered radiation dose and fractionation, as well as to further expand the sample size, to use a prospective study, and to observe the long-term efficacy of these techniques.

To investigate the association between tumor response to thoracic radiotherapy and epidermal growth factor receptor (EGFR) mutation status in patients with lung adenocarcinoma, we collected 48 patients treated between January 2010 and December 2013. Of the 18 patients with EGFR mutation, 15 (83.3%) had a single mutation, and three (16.7%) had double mutation. Different EGFR mutation subtypes exhibited different responses to radiotherapy. The identified double EGFR mutations were associated with reduction of residual tumor burden (RTB) after radiotherapy. In univariate analysis, EGFR mutations in exon 18, 20, and 21 and double EGFR mutation were significant factors predicting RTB. In multivariate analysis, exon 20 mutation was the only significant factor. Patients with EGFR mutation seemed to have longer mean overall survival (OS) compared to the group with wild-type EGFR (31.1 vs. 26.6 months, p=0.49). The median and mean OS in patients with double EGFR mutation vs. wild-type EGFR were 20.1 vs. 16.9 months and 28.9 vs. 26.6 months, respectively. Further studies with larger sample size are warranted to clarify the association of EGFR mutation status with the lung tumor response after radiotherapy.

Background: Adjuvant chemoradiotherapy is viewedas a definitive treatment after resection of stomach cancer (SC). To protectnormal tissue, several highly conformal radiotherapy modalities evolved.Therefore, we aimed to compare dosimetric parameters of helical tomotherapy(TOMO), volumetric-modulated arc therapy (VMAT), and intensity-modulatedradiotherapy (IMRT) in the adjuvant treatment of SC in different locations. Methods: This retrospective study wasconducted from January 2013 to May 2017 and included 11 patients with gastriccancer receiving adjuvant chemoradiotherapy after total gastrectomy. Both IMRTand VMAT plans were generated on the Pinnacle treatment planning system andTOMO plans were generated using a helical tomotherapy system. Adjuvantradiotherapy was prescribed with a total radiation dose of 50.4 Gy in 28fractions. Results: In proximal SC, TOMO achieved asignificantly lower dose for the heart, total kidney, left kidney, and liverthan that of IMRT or VMAT (P

Purpose To examine the safety and efficacy of Cyberknife stereotactic body radiation therapy (SBRT) and its effect on survival in patients of recurrent hepatocellular carcinoma (HCC). Methods and Materials This was a matched-pair study. From January 2008 to December 2009, 36 patients with 42 lesions of unresectable recurrent HCC were treated with SBRT. The median prescribed dose was 37 Gy (range, 25 to 48 Gy) in 4–5 fractions over 4–5 consecutive working days. Another 138 patients in the historical control group given other or no treatments were selected for matched analyses. Results The median follow-up time was 14 months for all patients and 20 months for those alive. The 1- and 2-year in-field failure-free rates were 87.6% and 75.1%, respectively. Out-field intrahepatic recurrence was the main cause of failure. The 2-year overall survival (OS) rate was 64.0%, and median time to progression was 8.0 months. In the multivariable analysis of all 174 patients, SBRT (yes vs. no), tumor size (≤4 cm vs. >4 cm), recurrent stage (stage IIIB/IV vs. I) and Child-Pugh classification (A vs. B/C) were independent prognostic factors for OS. Matched-pair analysis revealed that patients undergoing SBRT had better OS (2-year OS of 72.6% vs. 42.1%, respectively, p = 0.013). Acute toxicities were mild and tolerable. Conclusion SBRT is a safe and efficacious modality and appears to be well-tolerated at the dose fractionation we have used, and its use correlates with improved survival in this cohort of patients with recurrent unresectable HCC. Out-field recurrence is the major cause of failure. Further studies of combinations of SBRT and systemic therapies may be reasonable.

The aim of this study was to compare treatment plans of volumetric modulated arc therapy (VMAT) with intensity-modulated radiotherapy (IMRT) for all esophageal cancer (EC) tumor locations. This retrospective study from July 2009 to June 2014 included 20 patients with EC who received definitive concurrent chemoradiotherapy with radiation doses >50.4 Gy. Version 9.2 of Pinnacle3 with SmartArc was used for treatment planning. Dosimetric quality was evaluated based on doses to several organs at risk, including the spinal cord, heart, and lung, over the same coverage of gross tumor volume. In upper thoracic EC, the IMRT treatment plan had a lower lung mean dose (P = 0.0126) and lung V5 (P = 0.0037) compared with VMAT; both techniques had similar coverage of the planning target volumes (PTVs) (P = 0.3575). In middle thoracic EC, a lower lung mean dose (P = 0.0010) and V5 (P = 0.0145), but higher lung V20 (P = 0.0034), spinal cord Dmax (P = 0.0262), and heart mean dose (P = 0.0054), were observed for IMRT compared with VMAT; IMRT provided better PTV coverage. Patients with lower thoracic ECs had a lower lung mean dose (P = 0.0469) and V5 (P = 0.0039), but higher spinal cord Dmax (P = 0.0301) and heart mean dose (P = 0.0020), with IMRT compared with VMAT. PTV coverage was similar (P = 0.0858) for the 2 techniques. IMRT provided a lower mean dose and lung V5 in upper thoracic EC compared with VMAT, but exhibited different advantages and disadvantages in patients with middle or lower thoracic ECs. Thus, choosing different techniques for different EC locations is warranted.

Background: Intracranial solitary fibrous tumor was rare. However, most intracranial solitary fibrous tumors are benign, cerebral solitary fibrous tumor with malignant transformation was even more unusual. Case present: Herein, we presented a 55 year-old-male who was diagnosed intracranial solitary fibrous tumor five years ago. Partial tumor excision was performed via the pterional craniotomy. Unfortunately, one year later, cerebral solitary fibrous tumor with recurrence on latest operation was diagnosed via follow-up Magnetic Resonance imaging. Reopen the craniotomy site, subtotal removal of tumor and stereotactic radiation surgery were performed. However, four years later, a recurrent tumor was seen via follow-up computed topographic (CT) scans of brain with contrast. A third craniotomy with subtotal removal of tumor was performed. Pathological examination revealed solitary fibrous tumor with malignant transformation. Postoperative CyberKnife stereotactic radiosurgery was performed. One year after resection and CyberKnife stereotactic radiosurgery, a follow-up brain MR images showed tumor regression. Conclusion: Most of intracranial solitary fibrous tumors were benign lesions; however, physician should always keep in mind that malignant transformation may be found in intracranial solitary fibrous tumor.

Background: To analyze the local control of malignant lung tumors and survival of nonsmall cell lung cancer (NSCLC) patients after stereotactic ablative radiotherapy with CyberKnife. Materials and Methods: Patients with malignant lung tumors treated by CyberKnife between July 2007 and October 2010 at our institute were retrospectively reviewed. A total of 55 patients with 110 malignant lung tumors were included. There were 32 men and 23 women, and the median age was 67 years. There were 11 early-stage NSCLCs, while the other 44 patients with 99 lesions were metastatic lung tumors. The median gross tumor volume was 13.3 ml. Radiotherapy schedules include 40-60 Gy in 4-5 fractions, 45-60 Gy in 3 fractions and 30 Gy in 1 fraction. Results: The median follow-up time for patients alive was 34 months. The local control rates for all tumors were 96% at 1-year and 80% at 2 years. Univariate analysis demonstrated that target volume was important for local control. Biologically equivalent dose (BED) ≥100 Gy provided significantly higher chance to achieve a complete response than BED

The lumbar puncture is considered as a safe routine procedure in widespread clinical use for nearly a century. To the best of our knowledge, intracranial and intraspinal subarachnoid hemorrhage has never been reported as a complication after a lumbar puncture. We presented a case of a 76-year-old woman who fell in a deep coma after a lumbar puncture with diffuse subarachnoid hemorrhage and acute obstructive hydrocephalus on computed tomographic scans. Magnetic resonance imaging studies of the whole spine showed the hematoma spread along the spinal cord upward to the intracranial subarachnoid space. Remarkably, an extravasation of contrast medium presented at the level of L1 through L2, which was subsequently evaluated using the spinal angiography. There was an ongoing bleeding at the terminus of L1 lumbar segmental artery that lay within the spinal cord. Then a transarterial embolization followed and the hemorrhage stopped immediately. This case reminds us that although lumbar puncture is safe and simple, severe potential complication, such as intracranial and intraspinal subarachnoid hematoma, could occur.