A SwinTransformer-Based Segmentation Framework With Self-Supervised Strategy for Post-Operative Prostate Cancer Radiotherapy.

Radical prostatectomy (prostate removal) is a standard treatment for clinically localized prostate cancer and is often followed by postoperative radiotherapy. Postoperative radiotherapy requires accurate delineation of the clinical target volume (CTV) and lymph node drainage area (LNA) on computed tomography (CT) images. However, the CTV contour cannot be determined by the simple prostate expansion after resection of the prostate in the CT image. Constrained by this factor, the manual delineation process in postoperative radiotherapy is more time-consuming and challenging than in radical radiotherapy. In addition, CTV and LNA have no boundaries that can be distinguished by pixel values in CT images, and existing automatic segmentation models cannot get satisfactory results. Radiation oncologists generally determine CTV and LNA profiles according to clinical consensus and guidelines regarding surrounding organs at risk (OARs). In this work, we design a cascade segmentation block to explicitly establish correlations between CTV, LNA, and OARs, leveraging OARs features to guide CTV and LNA segmentation. Furthermore, inspired by the success of the self-attention mechanism and self-supervised learning, we adopt SwinTransformer as our backbone and propose a pure SwinTransformer-based segmentation network with self-supervised learning strategies. We performed extensive quantitative and qualitative evaluations of the proposed method. Compared to other competitive segmentation models, our model shows higher dice scores with minor standard deviations, and the detailed visualization results are more consistent with the ground truth. We believe this work can provide a feasible solution to this problem, making the postoperative radiotherapy process more efficient.

Timing theory continuous nursing, resistance training: Rehabilitation and mental health of caregivers and stroke patients with traumatic fractures.

BACKGROUND: Stroke is the leading cause of adult lifelong disability worldwide. A stroke is an acute cerebrovascular disease with a variety of causes and corresponding clinical symptoms. Around 75% of surviving stroke patients experience impaired nerve function, and some suffer from traumatic fractures, which can lead to special care needs. AIM: To determine the effect of timing theory continuous care, with resistance training, on the rehabilitation and mental health of caregivers and stroke patients with traumatic fractures. METHODS: Between January 2017 to March 2021, we selected 100 hospital admissions with post-stroke hemiplegia complicated with a traumatic fracture. Two participant groups were created: (1) Control group: given resistance training; and (2) Observation group: given timing theory continuous care combined with resistance training. The degree of satisfaction and differences in bone and phosphorus metabolism indexes between the two groups were compared. The self-perceived burden scale (SPBS) and caregiver burden questionnaire were used to evaluate the psychological health of patients and caregivers. The Harris hip function score, ability of daily living (ADL) scale, and global quality of life questionnaire (GQOL-74) were used to evaluate hip function, ability of daily living, and quality of life. RESULTS: Data were collected prior to and after intervention. Alkaline phosphatase (ALP), osteocalcin, and vitamin D3 in the observation group and control group increased after intervention (P < 0.05), and carboxy-terminal peptide of type I collagen ß Special sequence (ß-CTX) decreased (P < 0.05). ALP and osteocalcin in the observation group were higher than in the control group (P < 0.05). There was no significant difference in ß-CTX and vitamin D3 between the two groups (P > 0.05). The SPBS score of the observation group was lower and the ADL score was higher than the control group. The burden score was lower and the Harris hip function and GQOL-74 scores were higher than that of the control group (P < 0.05). The observation group's satisfaction rating was 94.00%, which was higher than the rating from the control group (P < 0.05). CONCLUSION: Timing theory continuous nursing with resistance training can reduce hip dysfunction in stroke patients with a traumatic fracture and enhance quality of life and mental health of patients and caregivers.

Prognostic significance of measurable residual disease based on multiparameter flow cytometry in childhood acute myeloid leukemia. / åŸºäºŽæµå¼ç»†èƒžæœ¯çš„å¯æµ‹é‡æ®‹ç•™ç— å¯¹å„¿ç«¥æ€¥æ€§é«“ç³»ç™½è¡€ç— é¢„åŽæ„ä¹‰çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To study the prognostic value of measurable residual disease (MRD) for childhood acute myeloid leukemia (AML) by analyzing MRD-guided risk stratification therapy. METHODS: A total of 93 children with AML were prospectively enrolled in this study. Chemotherapy with the 2015-AML-03 regimen was completed according to the risk stratification determined by genetic abnormality at initial diagnosis and MRD and bone marrow cytology after induction therapy I. Multiparameter flow cytometry was used to dynamically monitor MRD and analyze the prognostic effect of MRD on 3-year cumulative incidence of recurrence (CIR) rate, event-free survival (EFS) rate, and overall survival (OS) rate. RESULTS: The 93 children with AML had a 3-year CIR rate of 48%±6%, a median time to recurrence of 11 months (range 2-32 months), a 3-year OS rate of 65%±6%, and a 3-year EFS rate of 50%±5%. After induction therapy I and intensive therapy I, the MRD-positive children had a significantly higher 3-year CIR rate and significantly lower 3-year EFS and OS rates than the MRD-negative children (P<0.05). There were no significant differences in 3-year CIR, EFS, and OS rates between the MRD-positive children with a low risk at initial diagnosis and the MRD-negative children after adjustment of chemotherapy intensity (P>0.05). The multivariate analysis showed that positive MRD after intensive treatment I was a risk factor for 3-year OS rate in children with AML (P<0.05). CONCLUSIONS: MRD has predictive value for the prognosis of children with AML. Based on the MRD-guided risk stratification therapy, reasonable application of chemotherapy may improve the overall prognosis of children with AML.

Clinical features and prognosis of children with acute leukemias of ambiguous lineage under different diagnostic criteria. / ä¸åŒè¯Šæ–­æ ‡å‡†ä¸‹å„¿ç«¥æ€¥æ€§ä¸æ˜Žè°±ç³»ç™½è¡€ç— çš„ä¸´åºŠç‰¹ç‚¹å’Œé¢„åŽåˆ†æž.

OBJECTIVES: To study the clinical features and prognosis of children with acute leukemias of ambiguous lineage (ALAL) under different diagnostic criteria. METHODS: A retrospective analysis was performed on the medical data of 39 children with ALAL who were diagnosed and treated from December 2015 to December 2019. Among the 39 children, 34 received treatment. According to the diagnostic criteria for ALAL by World Health Organization and European Group for the Immunological Characterization of Leukemias, the 39 children were divided into two groups: ALAL group (n=28) and myeloid expression group (n=11). The clinical features, treatment, and prognosis were compared between the two groups. RESULTS: The 34 children receiving treatment had a 3-year event-free survival (EFS) rate of 75%±9% and an overall survival rate of 88%±6%. The children treated with acute myeloid leukemia (AML) protocol had a 3-year EFS rate of 33%±27%, those treated with acute lymphoblastic leukemia (ALL) protocol had a 3-year EFS rate of 78%±10%, and those who had no remission after induction with AML protocol and then received ALL protocol had a 3-year EFS rate of 100%±0% (P<0.05). The children with negative minimal residual disease (MRD) after induction therapy had a significantly higher 3-year EFS rate than those with positive MRD (96%±4% vs 38%±28%, P<0.05). Positive ETV6-RUNX1 was observed in the myeloid expression group, and positive BCR-ABL1, positive MLL-r, and hyperleukocytosis (white blood cell count ≥50×109/L) were observed in the ALAL group. There was no significant difference in the 3-year EFS rate between the myeloid expression and ALAL groups (100%±0% vs 66%±11%, P>0.05). CONCLUSIONS: ALL protocol has a better clinical effect than AML protocol in children with ALAL, and positive MRD after induction therapy suggests poor prognosis. Hyperleukocytosis and adverse genetic changes are not observed in children with myeloid expression, and such children tend to have a good prognosis, suggesting that we should be cautious to take it as ALAL in diagnosis and treatment.

[Second-generation Sequencing Analysis of Ph+ and Ph-like Childhood T-cell Acute Lymphoblastic Leukemia].

OBJECTIVE: To screen the core genes of Philadelphia chromosome positive/Ph like T-cell acute lymphoblastic leukemia (Ph+/Ph like T-ALL) using bioinformatics methods, and analyze the core sub-networks for exploration of the development process of Ph+/Ph like T-ALL, so as to find the molecular targets that may be used in clinical diagnosis and treatment. METHODS: The WES/RNA-seq examination results of Ph+/Ph-like T-ALL children had be collected in our hospital, the genetic data that met the requirements had be downloaded from GEO database, then GRO2R online differentially expressed gene screening program was used to screen differentially expressed genes, finally, GO function enrichment analysis and KEGG pathway enrichment analysis were performed to compare differentially expressed genes. At the same time, STRING database and Cytoscape software were used to build protein interaction network and screen hub genes and core sub-networks. RESULTS: For Ph+/Ph like T-ALL, a total of 84 differentially expressed genes had been found, for Ph+ ALL a total of 249 differentially expressed genes, and for T-ALL a total of 175 differentially expressed genes. Based on the results of GO function enrichment, KEGG pathway enrichment analysis and protein interaction network, RPA1, POLD1, POLE and SOCS1 were selected as hub genes. DNA damage repair and JAK/STAT signal transduction pathway were the main functional sub-networks. CONCLUSION: There are obviously abnormal DNA damage repair pathways in children with Ph+/Ph like T-ALL. RPA1, POLD1 and POLE may be important relevant biomarkers for the occurrence and development of Ph+/Ph like T-ALL, which can provide a basis for further research.

Bevacizumab Combined with S-1 and Raltitrexed for Patients with Metastatic Colorectal Cancer Refractory to Standard Therapies: A Phase II Study.

LESSONS LEARNED: Bevacizumab combined with S-1 and raltitrexed demonstrated positive antitumor efficacy and acceptable toxicity. This combination might represent a treatment option for refractory metastatic colorectal cancer. BACKGROUND: In patients with metastatic colorectal cancer (mCRC) refractory to standard therapies, S-1 plus raltitrexed showed a good objective response rate (ORR) and significant survival benefit in our previous study. In the present study, we assessed the activity and safety of bevacizumab combined with S-1 and raltitrexed. METHODS: This investigator-initiated, open-label, single-arm, phase II trial was performed at West China Hospital in China. Patients with mCRC who had disease progression after fluoropyrimidine, irinotecan, and oxaliplatin and had at least one measurable lesion were eligible for this trial. Anti-epidermal growth factor receptor (EGFR) (for tumors with wild-type RAS) and anti-vascular endothelial growth factor (VEGF) therapy in the first or second line was allowed, but patients who had been treated with bevacizumab across two consecutive chemotherapy regimens were excluded. Patients received bevacizumab (7.5 mg/kg on day 1), oral S-1 (80-120 mg per day for 14 days), and raltitrexed (3 mg/m2 on day 1) every 3 weeks. The primary endpoint was ORR. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: From September 2015 to November 2019, 44 patients were enrolled. Tumor response evaluation was available in 44 patients at the time of the analysis. There were no complete responses; the ORR was 15.9%, and the disease control rate was 54.5%. Median PFS and OS were 110 days (95% confidence interval [CI], 65.0-155.0) and 367 days (95% CI, 310.4-423.6), respectively. The combination was well tolerated. CONCLUSION: Bevacizumab combined with S-1 and raltitrexed showed promising antitumor activity and safety in refractory mCRC.

Correlation between serum cartilage oligomeric matrix protein and major adverse cardiovascular events within 30 days in patients with acute coronary syndrome.

BACKGROUND: We studied the correlation between cartilage oligomeric matrix protein (COMP) and major adverse cardiovascular events in patients with acute coronary syndrome (ACS) within 30 days. METHODS: This study included 170 ACS patients who were hospitalized in the Second Affiliated Hospital of Nantong University from August 2017 to April 2019. Serum COMP level was measured at baseline. The enrolled patients were followed up for 30 days and grouped according to the occurrence of major adverse cardiovascular events (MACE) during follow-up. Among the 170 patients, 23 patients had MACE during hospitalization (MACE group), and 147 patients had no MACE (no MACE group). RESULTS: The serum COMP levels in the MACE group were significantly higher than those of the non-MACE group [84.85 (51.55, 141.75) vs. 20.65 (9.11, 46.31) ng/mL, respectively, P<0.05]. The area under the receiver operating characteristic (ROC) curve for COMP in predicting the occurrence of MACE within 30 days was 0.839, with a cutoff level of 39.9 ng/mL [95% confidence interval (CI): 0.774-0.890], 86.96% sensitivity, and 72.79% specificity (P<0.0001). Multivariate logistic regression analysis showed that serum COMP could be used as an independent predictor of MACE within 30 days in ACS patients [odds ratio (OR): 1.024, 95% CI: 1.0133-1.0349, P=0.0001]. CONCLUSIONS: Serum COMP is associated with the short-term prognosis of ACS patients. High serum COMP levels can be used as a predictor of MACE within 30 days in ACS patients.

Chemoradiotherapy Is Inferior to Chemotherapy Alone in Adjuvant Setting for Signet Ring Cell Containing Gastric Cancer.

BACKGROUND: Signet ring cell containing gastric cancer (SRCGC) is a rare subtype of gastric cancer, and its adjuvant therapy is based on general gastric cancer. However, the effectiveness of radiotherapy for those SRCGC patients remains unknown. PURPOSE: The purpose of the study was to analyze whether the addition of radiotherapy to adjuvant chemotherapy (CT) can benefit survival in resected SRCGC patients. METHODS: Patients with SRCGC, who underwent D2 gastrectomy followed by adjuvant chemotherapy or chemoradiotherapy (CRT), were retrospectively collected. According to the proportion of signet ring cells, patients were histologically classified as pure SRCGC (pSRCGC) containing 100% of signet ring cells, mixed SRCGC (mSRCGC) containing >50% of signet ring cells, and contaminated SRCGC (cSRCGC) containing <50% of signet ring cells. Among the 272 patients, 156 were treated by CT alone and 116 by CRT. The primary endpoint was 3-year overall survival rate (3-year OS rate). RESULTS: With a median follow-up of 80.5 months, the 3-year OS rate was significantly higher in the CT group (70.5% vs. 58.6%, HR = 0.633, P = 0.017) compared with CRT group. Three independent characteristics were predictive of a poor overall survival: CRT treatment (P = 0.019), tumor size ≥5 cm (P < 0.001), and the presence of vessel invasion (P = 0.009). Subgroup analyses showed CRT significantly impaired prognosis in SRCGC patients in the cSRCGC subset, as well as lesions located in lower-middle sites, subtotal gastrectomy, male, <60 year, and no vessel invasion. Peritoneal was the most common recurrence site in SRCGC patients. The adverse events leukopenia and neutropenia were more common in the CRT group (P = 0.007). CONCLUSIONS: Adjuvant chemoradiotherapy was associated with poor survival compared with adjuvant chemotherapy in SRCGC patients with D2 gastrectomy.

[Serious adverse events associated with chemotherapy in children with acute lymphoblastic leukemia].

OBJECTIVE: To study the occurrence of serious adverse events (SAEs) related to chemotherapy with CCCG-ALL-2015 regimen in children with acute lymphoblastic leukemia (ALL) and the risk factors for death after the SAEs. METHODS: A retrospective analysis was performed on the medical data of 734 children with ALL. They were treated with CCCG-ALL-2015 regimen from January 2015 to June 2019. The occurrence of SAEs during the treatment was investigated. The children with SAEs were divided into a death group with 25 children and a survival group with 31 children. A multivariate logistic regression analysis was used to analyze the risk factors for death after the SAEs. RESULTS: Among the 734 children with ALL, 56 (7.6%) experienced SAEs (66 cases) after chemotherapy, among which 41 cases occurred in the stage of remission induction therapy. Of all 66 cases of SAEs, 46 (70%) were infection-related SAEs, including 25 cases of septic shock (38%), 20 cases of severe pneumonia (30%), and 1 case of severe chickenpox (2%), and 87% of the children with infection-related SAEs had neutrophil deficiency. The most common infection sites were blood and the lungs. The most common pathogens were Gram-negative bacteria, viruses, fungi, and Gram-positive bacteria. There were 16 cases (24%) of hemorrhage-related SAEs, with 11 cases of gastrointestinal bleeding (17%), 4 cases of pulmonary bleeding (6%), and 1 case of intracranial bleeding (2%). Of all 734 children with ALL, 66 (9.0%) died, among whom 25 died due to SAEs. The treatment-related mortality rate was 3.4%, and infection (72%) and bleeding (24%) were the main causes of death. Severe pneumonia was an independent risk factor for treatment-related death in ALL children (OR=4.087, 95%CI: 1.161-14.384, P=0.028). CONCLUSIONS: SAEs often occur in the stage of remission induction therapy, and infection-related SAEs are more common in ALL children accepting chemotherapy with CCCG-ALL-2015 regimen. The development of severe pneumonia suggests an increased risk for death in these children.

Primary hepatic follicular dendritic cell sarcoma: A case report.

BACKGROUND: Follicular dendritic cell sarcoma (FDCS) is an uncommon type of tumor with low incidence. To date, no standard treatment for the disease has been established. Surgery remains the main treatment. Adjuvant chemotherapy and radiotherapy are optional approaches. Metastatic cases require multidisciplinary collaborative treatments. However, the choice of chemotherapeutic drugs is controversial. CASE SUMMARY: A 66-year-old Chinese woman presented to our hospital complaining of intermittent pain of right upper quadrant. An enhanced computed tomography (CT) scan of the abdomen revealed hepatocellular carcinoma. Subsequently, the patient underwent a radical partial hepatectomy. Primary FDCS of the liver was diagnosed pathologically. Except for regular follow-up examinations, the patient did not receive adjuvant chemotherapy or radiotherapy. However, fluorine-18-fluorodeoxyglucose positron emission tomography/CT (PET/CT) confirmed lymph node metastases in the space of ligamentum hepatogastricum and pancreatic head, as well as the portacaval space. The patient was given systemic chemotherapy with gemcitabine and docetaxel for she was unsuitable for surgery. Satisfactorily, the metastatic lymph nodes were significantly reduced to clinical complete remission after eight cycles of chemotherapy. Then, strengthened radiotherapy was followed when the patient rejected the opportunity of surgery. Eventually, the carcinoma got better control and the patient was free of progression. CONCLUSION: This case highlights the importance of making suitable chemotherapy regimens for the rare tumor. The combination of gemcitabine, docetaxel, and consolidated radiotherapy may offer a new promising option for the treatment of metastatic hepatic FDCS in the future.

S-1 plus Raltitrexed for Refractory Metastatic Colorectal Cancer: A Phase II Trial.

LESSONS LEARNED: The upregulation of dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) are important mechanisms of resistance to 5-fluorouracil (5-FU) in metastatic colorectal cancer (mCRC) after long exposure to 5-FU.S-1 (containing a DPD inhibitor) combined with raltitrexed (a TS inhibitor) showed a moderate effect, which needs further study as a third- or later-line therapy in mCRC. BACKGROUND: 5-fluorouracil (5-FU) is a fundamental drug in the treatment of metastatic colorectal cancer (mCRC). Patients with mCRC are often exposed to 5-FU and/or its analogues for a long time because of its central role in treatment regimens. The upregulation of dihydropyrimidine dehydrogenase (DPD) and/or thymidylate synthase (TS) are important mechanisms of resistance of 5-FU. To evaluate the efficacy and safety of S-1 (containing a DPD inhibitor) and raltitrexed (a TS inhibitor) for refractory mCRC, a one-center, single-arm, prospective phase II trial was conducted. METHODS: Patients who had mCRC that had progressed after treatment with fluoropyrimidine, irinotecan, and oxaliplatin and who had at least one measurable lesion were eligible for this trial. Patients received oral S-1 (80-120 mg for 14 days every 3 weeks) plus an intravenous infusion of raltitrexed (3 mg/m2 on day 1 every 3 weeks). The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: In total, 46 patients were enrolled. Three patients did not complete the first assessment because of adverse events and unwillingness, leaving tumor response evaluation available in 43 patients. Of 43 evaluable patients, the ORR was 13.9% and disease control rate was 58.1%. In the intention-to-treat population (n = 46), the ORR was 13.0% and disease control rate was 54.3%. Median PFS and median OS were 107 days (95% confidence interval [CI], 96.3-117.7) and 373 days (95% CI, 226.2-519.8), respectively. Most of the adverse effects were mild to moderate. CONCLUSION: S-1 combined with raltitrexed for refractory mCRC showed moderate effect, and it is worthy of further study as third- or later-line therapy in mCRC.

Ovarian cancer treatment with a tumor-targeting and gene expression-controllable lipoplex.

Overexpression of folate receptor alpha (FRα) and high telomerase activity are considered to be the characteristics of ovarian cancers. In this study, we developed FRα-targeted lipoplexes loaded with an hTERT promoter-regulated plasmid that encodes a matrix protein (MP) of the vesicular stomatitis virus, F-LP/pMP(2.5), for application in ovarian cancer treatment. We first characterized the pharmaceutical properties of F-LP/pMP(2.5). The efficient expression of the MP-driven hTERT promoter in SKOV-3 cells was determined after an in-vitro transfection assay, which was significantly increased compared with a non-modified LP/pMP(2.5) group. F-LP/pMP(2.5) treatment significantly inhibited the growth of tumors and extended the survival of mice in a SKOV-3 tumor model compared with other groups. Such an anti-tumor effect was due to the increased expression of MP in tumor tissue, which led to the induction of tumor cell apoptosis, inhibition of tumor cell proliferation and suppression of tumor angiogenesis. Furthermore, a preliminary safety evaluation demonstrated a good safety profile of F-LP/pMP(2.5) as a gene therapy agent. Therefore, FRα-targeted lipoplexes with therapeutic gene expression regulated by an hTERT promoter might be a promising gene therapy agent and a potential translational candidate for the clinical treatment of ovarian cancer.

The Effects of ASMase Mediated Endothelial Cell Apoptosis in Multiple Hypofractionated Irradiations in CT26 Tumor Bearing Mice.

BACKGROUND: To investigate the effects of ASMase mediated endothelial cell apoptosis in multiple hypofractionated irradiations in CT26 tumor bearing mice. MATERIALS AND METHODS: Thirty-five CT26 tumor bearing mice were subjected to single ionizing radiation (IR) of 0, 3, 6, 9, 12, 15, 18 Gy. Eight hours after IR, the mice were sacrificed and tumor tissues were used for CD31 immunohistochemistry staining, TUNEL and CD31 double staining, ASMase activity assay. Then 6 and 12 Gy were chosen for multiple hypofractionated IR experiments according to the above results. Each time after IR, 5 mice were sacrificed and assayed as above. RESULTS: The ASMase activities were increased significantly after a single IR of 12 Gy or higher which was accompanied with remarkable increased endothelial cell apoptosis and decreased MVD. For 6 Gy which was not high enough to trigger ASMase activation, after 2 or more times of IR, the ASMase activities were significantly increased accompanied with remarkable increased endothelial cell apoptosis and decreased MVD. While for 12 Gy, after 2 or more times of IR, the ASMase activities and endothelial cell apoptosis rates were maintained without remarkable increase; however, the MVD was significantly decreased. What's more, the cancer cell apoptosis rates were significantly increased after multiple IR for both 6 Gy and 12 Gy. CONCLUSIONS: ASMase mediated endothelial cell apoptosis may play an important role in the process of multiple hypofractionated IR for CT26 colorectal carcinoma.

Phase I study of postoperative radiotherapy concurrent with S-1 in patients with gastric cancer.

Postoperative chemoradiotherapy (CRT) with concurrent 5-fluorouracil is the standard care for gastric cancer patients after curative surgery. The previous studies revealed that the subgroup of patients with high recurrence risk would benefit most from adjuvant CRT. S-1, a novel oral fluorouracil, has showed very effective in metastatic gastric cancer and became the standard option for gastric cancer with D2 dissection. The safety and dosage of S-1 combined with postoperative radiotherapy have not yet been evaluated. This study is to determine the maximum tolerate dose (MTD) and dose-limiting toxicity (DLT) of S-1 given concurrently with postoperative high-dose radiotherapy in gastric cancer. Patients with more advanced stage (pT4 and/or pN+) after R0 resection were recruited. Eligible patients received one cycle standard SOX (S-1 plus oxaliplatin) chemotherapy, then S-1 monotherapy with concurrent radiotherapy for 6 weeks, followed by additional three cycles of SOX. During the concurrent CRT, S-1 was administered on every radiotherapy treatment day according to a predefined dose-escalation schedule. Radiotherapy (3D-RT or IMRT) was given to a total dose of 50.4 Gy in 28 fractions. DLT was defined as grade 3 or 4 hematologic and non-hematologic toxicity. From March 2011 to October 2012, 21 patients were enrolled at five dose levels: 40 (n = 3), 50 (n = 3), 60 (n = 6), 70 (n = 6) and 80 mg/m(2)/day (n = 3). D2-dissection was performed in 18 patients (85.7 %) and 15 patients (71.4 %) had stage III disease. The most common dose-related toxicity was anorexia, nausea and vomiting, fatigue and leucopenia. DLT was occurred in one patient at 60 mg/m(2)/day (grade 3 fatigue), one patient at 70 mg/m(2)/day (grade 3 vomiting and anorexia), two patients at 80 mg/m(2)/day (one with grade 3 vomiting and anorexia; another with grade 3 febrile leucopenia). Four patients did not complete CRT as planned. Overall, this phase I study demonstrated that postoperative CRT with daily S-1 was feasible in gastric cancer and the MTD of S-1 concurrent with radiotherapy was 70 mg/m(2)/day. This S-1-based postoperative CRT will be investigated in a multicenter phase III study in West China.

Bone marrow mesenchymal stem cell-derived Wnt5a inhibits leukemia cell progression in vitro via activation of the non-canonical Wnt signaling pathway.

Leukemia is one of the most common malignancies in humans worldwide; however, the molecular mechanism of the effect of bone marrow mesenchymal stem cells (bMSCs) on leukemia cell growth remains unclear. The present study demonstrated that Wnt5a protein expression was significantly induced in bMSCs via an adenovirus vector (P<0.01). The results showed that the proliferation of HL60 cells, a leukemia cell line, was significantly inhibited when the cells were stimulated with the culture supernatant of adeno-Wnt5a bMSCs compared with the culture supernatants of bMSCs and adeno-vector bMSCs for 24 or 48 h (P<0.01). The promoted maturation levels of HL60 cells were also observed following stimulation with the culture supernatant of adeno-Wnt5a bMSCs (P<0.01). However, no significant difference was identified in the proliferation and maturation of HL60 cells among the three groups stimulated with the culture supernatants containing a neutralization antibody against Wnt5a. Furthermore, the bMSC-derived Wnt5a was found to influence the maturation and proliferation of the HL60 cells by enhancing the non-canonical Wnt signaling pathway, while inhibiting the canonical Wnt signaling pathway by upregulating the expression of receptor tyrosine kinase-like orphan receptor 2 and calcium/calmodulin-dependent protein kinase II, and suppressing the expression of ß-catenin and cyclin D1. In conclusion, bMSC-derived Wnt5a modifies the proliferation and maturation of HL60 cells via activation of the non-canonical Wnt signaling pathway.

Postoperative chemoradiotherapy in gastric cancer: a phase I study of radiotherapy with dose escalation of oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX regimen).

Concurrent chemoradiotherapy begins to be more and more widely accepted as a standard adjuvant treatment in gastric cancer. And oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) also reveals to be a very effective regimen in gastric cancer. But the safety and the dosages of FOLFOX combining with radiotherapy are still unknown. This study was to determine the maximum-tolerated dose and the dose-limiting toxicity of FOLFOX with higher-dose concurrent radiotherapy (RT) as adjuvant treatment in patients with gastric cancer. Patients with Stage II/III gastric cancer after surgery were recruited. They received one cycle of induction chemotherapy (standard FOLFOX4). Then, they received 50.4 Gy in 1.8-Gy fractions in combination with two cycles of concurrent FOLFOX, and oxaliplatin among this regimen was administered with escalating doses. Dose-limiting toxicity including grade 3 or grade 4 hematologic and nonhematologic toxicities was investigated. Fifteen patients were enrolled at the following dose levels: oxaliplatin 55 mg/m(2) (3 patients), 65 mg/m(2) (6 patients), and 75 mg/m(2) (6 patients). Dose-limiting toxicity was observed in 1 patient at 65 mg/m(2) (grade 4 leukopenia) and in 3 patients at 75 mg/m(2) (1 patient had grade 4 leukopenia, 1 had grade 3 thrombocytopenia, and 1 had grade 3 stomatitis). Combination chemotherapy FOLFOX with oxaliplatin 65 mg/m(2), d 1; leucovorin 200 mg/m(2), 2 h, d1-2; 5-fluorouracil 400 mg/m(2), iv, d 1-2 and 600 mg/m(2) civ, 22 h, d 1-2 given concurrently with RT (50.4 Gy) can be recommended as a safer and preferable regimen for the adjuvant treatment of patients with gastric cancer.

[Growth and differentiation effect on HL60 cells by adenovirus-mediated exogenous wnt5a gene modification on human bone marrow mesenchymal stem cells].

OBJECTIVE: To study the effect of human bone marrow mesenchymal stem cell (bMSCs) modified by the adenovirus-mediated exogenous wnt5a gene on the hematopoietic function of bone marrow and the inhibition of the growth of HL60 leukemia cells. METHODS: BMSCs were identified through flow cytometry and modified by Ad5-wnt5a, The transfection rate of wnt5a gene in bMSCs was detected by RT-PCR. The cell growth curves were detected in different groups (bMSCs group, Ad5-GFP group, Ad5-wnt5a group). Ad5-wnt5a-bMSCs and HL60 cells were co-cultured, the surface differentiation antigen (CD13, CD14, CD68) and cell cycles were detected by immunocytochemical and flow cytometry in different groups (HL60 cell group, HL60+bMSCs group, HL60+ Ad5-GFP group, HL60+ Ad5-wnt5a group), respectively. RESULTS: Adenovirus-mediated exogenous wnt5a gene was transfected into bMSCs. The expression of differentiation antigens of CD14, CD68 in HL60+Ad5-wnt5a group were higher than those in control group (P < 0.05), the expression of differentiation antigen CD13 were not significant difference in different groups (P > 0.05). Compared with control group, the cell cycle in HL60+ Ad5-wnt5a group was blocked at G2 phase in the fourth day. CONCLUSION: Exogenous wnt5a gene can promote the growth of bMSCs, and induce HL60 cells to differentiation and maturation.

[Interfractional and intrafractional setup errors in radiotherapy for tumors analyzed by cone-beam computed tomography].

BACKGROUND & OBJECTIVE: Both interfractional and intrafractional setup errors may affect the precision of radiotherapy. This study was to analyze the interfractional and intrafractional setup errors in radiotherapy for tumors using cone-beam computed tomography(CBCT). METHODS: Of the 51 patients received radiotherapy, 19 had head and neck tumors, 25 had thoracic tumors, and seven had abdominal-pelvic tumors. Patients received CBCT scans after initial setup, after re-positioning and after radiation delivery. The CBCT images were registered to the planning CT images, and setup errors on X,Y, Z axes were analyzed. RESULTS: A total of 1,934 CBCT scans were performed on 51 patients, of which 955 were performed after initial setup, 525 after re-positioning and 454 after radiation delivery. The interfractional setup errors on X, Y and Z axes were (1.2+/-0.9) mm,(1.2+/-1.1) mm and (1.0+/-0.8) mm, respectively, for head and neck tumors; (2.3+/-1.9) mm, (4.2+/-3.7) mm and (2.4+/-2.1) mm, respectively, for thoracic tumors; (1.7+/-1.5) mm,(4.7+/-3.6) mm and (2.1+/-1.6) mm, respectively, for abdominal-pelvic tumors. Comparing with the post-correction position, the post-treatment setup errors in head and neck tumors increased significantly on all three axes (P < 0.05), whereas the difference was not significant in trunk tumors (P > 0.05). CONCLUSIONS: Measurement and correction of interfractional setup errors before each fraction using CBCT could help to improve the precision of radiotherapy. The intrafractional setup error variations are obvious in head and neck tumors and should be taken into account during treatment planning. The intrafractional setup errors in trunk tumors need further study.