Outcomes Following Cytoreductive Surgery and Hyperthermic Intraoperative Thoraco-Abdominal Chemotherapy with Diaphragm Resection for Peritoneal Carcinomatosis: A Retrospective Cohort Study.

PURPOSE: We aimed to evaluate the safety and efficacy of hyperthermic intraoperative thoraco-abdominal chemotherapy (HITAC) and cytoreductive surgery (CRS) for peritoneal carcinomatosis (PC) patients who underwent diaphragm resection. METHODS: PC patients who underwent CRS with diaphragm resection were selected from a prospectively established database and were divided into hyperthermic intraperitoneal chemotherapy (HIPEC) and HITAC groups. The clinicopathological characteristics, treatment-related variables, perioperative adverse events (AEs), and survival outcomes were compared between the two groups. RESULTS: Of 1168 CRS + HIPEC/HITACs, 102 patients were enrolled-61 HITAC patients and 41 HIPEC patients. In the HITAC and HIPEC groups, the incidence of grade III-V AEs was 29.5% versus 34.1% (p = 0.621). The pleural progression rates were 13.2 versus 18.9% (p = 0.462) and the median overall survival (OS) was 50.5 versus 52.7 months (p = 0.958). Median time to progression (TTP) in thoracic disease was not reached. There was no significant difference in perioperative AEs, TTP, and OS for total patients and the completeness of cytoreduction (CC) score subgroups (p > 0.05). Age ≥ 60 years (hazard ratio [HR] 4.162, p = 0.026) was an independent risk factor influencing pleural progression, and primary malignant peritoneal mesothelioma (MPM; HR 2.749, p = 0.016) and the presence of two or more serious AEs (SAEs; HR 7.294, p = 0.001) were independent risk factors influencing OS. CONCLUSIONS: HITAC can be performed in carefully selected PC patients who underwent diaphragm resection, with no worsening of the safety profile and a possible benefit for pleural progression. In those patients, age ≥ 60 years is associated with a shorter TTP of thoracic disease, while primary MPM and two or more perioperative SAEs are associated with worse OS.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal metastasis from breast cancer: a preliminary report of 4 cases.

BACKGROUND: Breast cancer (BC) has the highest morbidity and the fifth-highest mortality rate among women in China. Peritoneal metastases from BC are rare, and presently, there are no guidelines or international consensus on its treatment. Patients with a prognosis of peritoneal carcinomatosis (PC) have poorer survival rates than patients with other regional metastases from BC. METHODS: Four BC PC patients, who had undergone cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC), participated in this study. Clinicopathologic characteristics and overall survival (OS) data were collected and analyzed. RESULTS: Patients' average age when they underwent CRS + HIPEC was 59.8 years. The average time of CRS + HIPEC was 8.8 h. The median number of resected organ areas was 7. Following CRS + HIPEC, each of the 4 patients survived for 31, 28, 16 and 52 months, respectively. There were no serious adverse events during the perioperative period. CONCLUSIONS: The study examined the detailed process of CRS + HIPEC and found that patients with BC PC may benefit from this treatment. The 4 cases provided evidence that the integrated therapy of CRS + HIPEC is a promising strategy that could improve outcomes for BC PC patients. Further, no serious adverse events (SAEs) occurred during the CRS + HIPEC perioperative period.

Peritoneal cancer index (PCI) based patient selecting strategy for complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy in gastric cancer with peritoneal metastasis: A single-center retrospective analysis of 125 patients.

OBJECTIVE: The role of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer with peritoneal metastasis (GCPM) is still controversial, mainly due to the limited survival benefit and uncertain patient selection. This study aims to construct a selecting strategy in GCPM for CRS + HIPEC. METHODS: From a prospective established database, 125 patients were enrolled. All these patients were pathologically confirmed as GCPM and treated with CRS + HIPEC with or without preoperative or postoperative chemotherapy. The clinical documents and follow-up results were collected and analyzed with the primary endpoint of overall survival (OS) and the secondary endpoint of perioperative serious adverse events (SAEs). RESULTS: The median OS of 125 GCPM patients treated with CRS + HIPEC was 10.7 months, with 1-, 2-, 3-, and 5-year survival rates of 43.8%, 24.7%, 18.6%, and 15.7%, respectively. The multivariate analysis identified completeness of cytoreduction (CC), SAEs, HIPEC drugs, and adjuvant chemotherapy as independent prognostic factors on OS. The median OS was 30.0 (95%CI: 16.8-43.3) months in CC-0 group, significantly better than 7.3 (95%CI: 5.8-8.8) months in CC1-3 group (P < 0.001). The median OS showed no significant difference among CC-1 (8.5, 95%CI: 6.7-10.2, months), CC-2 (5.6, 95%CI: 3.0-8.2, months) and CC-3 (6.5, 95%CI: 5.2-7.7, months) groups (P > 0.05 for all pairwise comparations). The nomogram based on peritoneal metastasis timing, preoperative tumor marker (TM), and peritoneal cancer index (PCI), with AUC of 0.985, showed a good accuracy and consistency between actual observation and prediction of the probability of complete CRS. The cutoffs of PCI were 16 for synchronous GCPM with normal TM, 12 for synchronous GCPM with abnormal TM, 10 for metachronous GCPM with normal TM, and 5 for metachronous GCPM with abnormal TM, setting the probability to achieve complete CRS as 50%. CONCLUSIONS: Only complete CRS + HIPEC (CC-0) could improve survival for high selected GCPM patients with acceptable safety. An incomplete CRS (CC1-3) should be avoided for GCPM patients. Synchronous GCPM with PCI ≤16 and normal TM, synchronous GCPM with PCI ≤12 and abnormal TM, metachronous GCPM with PCI ≤10 and normal TM, or metachronous GCPM with PCI ≤5 and abnormal TM maybe potential indications for complete CRS + HIPEC treatment.

Efficacy and safety of concurrent anti-tuberculosis treatment and chemotherapy in lung cancer patients with co-existent tuberculosis.

BACKGROUND: This retrospective study evaluated the safety and efficacy of concurrent anti-tuberculosis (TB) and chemotherapy treatment in patients with advanced lung cancer and active TB. METHODS: We retrospectively analyzed patients who were first diagnosed with advanced lung cancer and received first-line chemotherapy in Guangzhou Chest Hospital from 2015 to 2017. Patients were categorized into two groups (2:1): lung cancer patients without active TB (Group A), and lung cancer patients with active TB (Group B). Primary endpoints included adverse events (AEs), objective response rate (ORR), time to treatment failure, and overall survival (OS). RESULTS: A total of 99 patients were eligible (Group A, n=66; Group B, n=33). Grade ≥3 treatment-related AEs, primarily hematologic toxicity, occurred in 39.4% and 51.5% of patients in Groups A and B, respectively. The hypohepatia in both groups was generally at grade 1 or 2, with similar incidences (26% and 27%, respectively). After two cycles of chemotherapy, the ORR was 42.4% and 33.3% in Group A and B, respectively (P=0.383). The median time to treatment failure (TTF) was 7.0 and 5.6 months for Groups A and B, respectively (P=0.175). The median OS was 17.0 and 14.0 months for Groups A and B, respectively (P=0.312). After 3 months of anti-TB treatment, all patients achieved sputum acid-fast bacilli (AFB) smear conversion and absorption on imaging, and the end of follow-up observed no recurrence. CONCLUSIONS: Concurrent anti-TB and chemotherapy treatment did not increase hematological toxicity or hypohepatia in lung cancer patients with pulmonary TB.

Treatment of early-onset scoliosis: techniques, indications, and complications.

The treatments for early-onset scoliosis (EOS) remain great challenges for spine surgeons. This study aimed to comprehensively review the treatments for EOS, especially the advancements made in the last decade. Current studies on EOS were retrieved through a search on PubMed, UpToDate, the Web of Science Core Collection and Scopus were reviewed. The most pertinent information related to the current treatments for EOS was collected. The foci of treatments for EOS have included creating a well-developed thoracic cavity, improving lung volume, and improving pulmonary function. Conservative treatments include bracing, casting, halo-gravity traction, and physiotherapy. Serial casting is the most effective conservative treatment for EOS. Surgical treatments mainly include growth-friendly techniques, which are generally classified into three types according to the amount of correction force applied: distraction-based, compression-based, and growth-guided. The distraction-based systems include traditional or conventional growing rods, magnetically controlled growing rods, and vertical expandable prosthesis titanium ribs. The compression-based systems include vertebral body stapling and tethering. The growth-guided systems include the Shilla system and modern Luque trolley. In addition, some newer techniques have emerged in recent years, such as posterior dynamic deformity correction (ApiFix). For EOS patients presenting with sharp deformities in a long, congenital spinal deformity, a hybrid technique, one-stage posterior osteotomy with short segmental fusion and dual growing rods, may be a good choice. Hemivertebra resection is the gold standard for congenital scoliosis caused by single hemivertebra. Although the patient's growth potential is preserved in growth-friendly surgeries, a high complication rate should be expected, as well as a prolonged treatment duration and additional costs. Knowledge about EOS and its treatment options is rapidly expanding. Conservative treatments have specific limitations. For curves requiring a surgical intervention, surgical techniques may vary depending on the patients' characteristics, the surgeon's experience, and the actual state of the country.

Toward an Expert Level of Lung Cancer Detection and Classification Using a Deep Convolutional Neural Network.

BACKGROUND: Computed tomography (CT) is essential for pulmonary nodule detection in diagnosing lung cancer. As deep learning algorithms have recently been regarded as a promising technique in medical fields, we attempt to integrate a well-trained deep learning algorithm to detect and classify pulmonary nodules derived from clinical CT images. MATERIALS AND METHODS: Open-source data sets and multicenter data sets have been used in this study. A three-dimensional convolutional neural network (CNN) was designed to detect pulmonary nodules and classify them into malignant or benign diseases based on pathologically and laboratory proven results. RESULTS: The sensitivity and specificity of this well-trained model were found to be 84.4% (95% confidence interval [CI], 80.5%-88.3%) and 83.0% (95% CI, 79.5%-86.5%), respectively. Subgroup analysis of smaller nodules (<10 mm) have demonstrated remarkable sensitivity and specificity, similar to that of larger nodules (10-30 mm). Additional model validation was implemented by comparing manual assessments done by different ranks of doctors with those performed by three-dimensional CNN. The results show that the performance of the CNN model was superior to manual assessment. CONCLUSION: Under the companion diagnostics, the three-dimensional CNN with a deep learning algorithm may assist radiologists in the future by providing accurate and timely information for diagnosing pulmonary nodules in regular clinical practices. IMPLICATIONS FOR PRACTICE: The three-dimensional convolutional neural network described in this article demonstrated both high sensitivity and high specificity in classifying pulmonary nodules regardless of diameters as well as superiority compared with manual assessment. Although it still warrants further improvement and validation in larger screening cohorts, its clinical application could definitely facilitate and assist doctors in clinical practice.

[Shear wave elastography for guiding prostate puncture and differential diagnosis of prostatic lesions].

OBJECTIVE: To assess the value of transrectal shear wave elastography (SWE) in improving the detection of PCa and differentiating benign from malignant prostatic lesion. METHODS: We performed transrectal ultrasonography (TRUS) and SWE for 83 PCa-suspected patients and measured the maximum (Emax) and mean elastic modulus (Emean) of the lesions. In addition to conventional "6+X" puncture, we conducted SWE-guided prostate puncture and evaluated SWE in improving the detection rate of PCa based on the pathological results. Then, we obtained the threshold value of the Emax using the ROC curve and analyzed its correlation with the clinicopathological data. RESULTS: SWE-guided puncture was completed in all the 83 patients, of whom 31 were pathologically diagnosed with PCa and the other 52 with BPH. Compared with the BPH patients, the men with PCa showed significantly higher values of Emax (ï¼»47.13 ± 9.95ï¼½ vs ï¼»63.70 ± 14.29ï¼½ kPa, P < 0.05) and Emean (ï¼»33.25 ± 4.61ï¼½ vs ï¼»43.04 ± 8.57ï¼½ kPa, P < 0.05). The area under the ROC curve of Emax was 0.913, with a sensitivity of 90.1% and a specificity of 80.2%, with 54.15 kPa as the diagnostic threshold. The positive rates of PCa detected by SWE-guided puncture and single-needle puncture were 32.53% and 72.38%, respectively, significantly higher than 28.92% and 17.27% by TRUS-guided puncture and single-needle puncture (P < 0.05). Compared with TRUS, SWE exhibited a remarkably higher sensitivity (54.84% vs 80.65%, P < 0.05), specificity (67.31% vs 86.54%, P < 0.05), accuracy (62.65% vs 84.34%, P < 0.05), positive predictive value (50.00% vs 78.13%, P < 0.05) and negative predictive value (71.43% vs 88.26%, P < 0.05) in the differential diagnosis of benign and malignant prostatic lesions. Emax was positively correlated with the Gleason scores of the PCa patients. CONCLUSIONS: SWE can help determine the biopsy target, improve the detection of PCa and differentiate PCa from BPH.

[Safety of A 60-minute Rituximab Rapid Infusion Protocol for Adult B-cell Lymphoma Patients:A Single-center Single Arm Clinical Trail].

Objective To investigate the safety of a 60-minute rituximab rapid infusion protocol in the maintenance therapy for Chinese B-cell lymphoma patients (including the elderly) and to discuss the feasibility of rituximab treatment in outpatient departments or daily wards. Methods This prospective study enrolled 820 patients diagnosed with B cell lymphoma in the Department of Hematology of Peking Union Medical College Hospital from February 2015 to July 2016. From the second chemotherapy cycle,rituximab was infused within 60 minutes (100 mg/h over the first 15 minutes and the remaining dose given over 45 minutes, there was no maximum infusion rate,and 700 mg/h was acceptable),and the adverse reactions were recorded. Comparison was done between patients<65 years and≥65 years. Results The overall adverse reaction rate was 4.20% and no grade 4 or higher adverse reactions were recorded. The adverse reaction rate in the elderly patients was not significantly elevated. Conclusion For Chinese patients (including the elderly) with B cell lymphoma,the 60-minute rapid infusion of rituximab (beyond the first cycle) is a safe treatment option with low adverse reaction rate.

Treatment of hypermyoglobinemia after CRS + HIPEC for patients with peritoneal carcinomatosis: A retrospective comparative study.

This retrospective comparative study aims to explore the time courses of serum myoglobin (Mb) changes, and summarize our experience in treating patients with hypermyoglobinemia after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).This study covered 60 patients with peritoneal carcinomatosis treated with CRS + HIPEC as the study group, and another 25 cancer patients treated with conventional extensive surgery without HIPEC as the control group from February to October 2016. In the study group, patients with postoperative hypermyoglobinemia were on a comprehensive treatment regimen consisting intravenous injection of sodium bicarbonate solution according to the Mb level. In the control group, patients were recorded and treated with the same regimen except for special sodium bicarbonate solution. The preoperative and postoperative serum Mb, blood urine nitrogen (BUN), and creatinine (Cr) levels were evaluated.There were no significantly difference between the 2 groups in serum Mb, BUN, and Cr levels before surgery. Postoperative serum Mb levels were elevated in both groups and significantly higher on postoperative 0 to 2 days (P < .05) in the study group than the control group. The peak value of serum Mb levels (426.65 ±â€Š108.386 µg/L) occurred on the surgery day. The serum Mb change rate was much bigger in the study group than the control group. Serum BUN levels in both groups revealed a slow increase during the early postoperative period and were significantly lower in the study group than the control group on days 1 and 2. The serum Cr levels were similar and stable between the 2 groups after surgery. The serum Cr change rates changed synchronously with same tendency in both groups, and on postoperative day 1 the increase rate was bigger in the control group than the study group.Hypermyoglobinemia is a common and prominent lab abnormality after CRS + HIPEC, and serum Mb levels could be an early and sensitive indicator for dramatic disturbances in the internal milieu after CRS + HIPEC. Adequate treatment with sodium bicarbonate could accelerate the reduction in serum Mb levels and reduce the risk for major organ damages.

Novel homozygous PANK2 mutation identified in a consanguineous Chinese pedigree with pantothenate kinase-associated neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive neurodegenerative disorder resulting from pantothenate kinase 2 (PANK2) gene mutations. It is clinically characterized by early onset of extrapyramidal symptoms, with or without pigmentary retinopathy, optic atrophy and acanthocytosis. The specific radiographic appearance of PKAN is the eye-of-the-tiger sign. However, there are few studies regarding PKAN patients of Chinese Han ancestry. In the present study, a Chinese 20-year-old female with an 8-year history of unsteady walking and involuntary movements is described. Brain magnetic resonance imaging revealed eye-of-the-tiger sign. Following sequencing of PANK2, a novel homozygous c.863C>T (p.P288L) mutation was identified in the patient and heterozygous c.863C>T was identified in her consanguineous parents. The absence of this mutation in the 1000 Genomes database, The Exome Aggregation Consortium, and 200 controls demonstrated that this mutation was probably pathogenic for PKAN in this family. In addition, the PANK2 c.863C>T mutation was predicted to be deleterious by SIFT, disease causing by Mutation Taster and probably damaging by PolyPhen2.

Expression of ATP binding cassette E1 enhances viability and invasiveness of lung adenocarcinoma cells in vitro.

ATP binding cassette E1 (ABCE1), a member of the family of ATP binding cassette transporters, has initially emerged as an RNase L inhibitor. As a highly conserved protein, it is involved in capsid assembly and translation processes of the human immunodeficiency virus as well as in tumor development and progression. Studies have shown that ABCE1 protein was overexpressed in lung carcinoma tissues and metastatic lymph nodes compared to normal lung tissues. However, little is known about the roles of ABCE1 in lung cancer. The present study investigated the biological effects of vector-mediated ABCE1 overexpression in lung cancer cells in vitro and examined the underlying molecular mechanisms. Overexpression of ABCE1 in the LTEP­a-2 lung adenocarcinoma cell line was achieved by transfection with a plasmid containing full­length ABCE1 cDNA. The ectopic expression of ABCE1 was shown to promote the viability and invasive capacity of lung cancer cells, and to in reduce p27 expression. However, overexpression of ABCE1 did not significantly affect the cell cycle distribution. In conclusion, the present study suggested that ABCE1 promotes the growth, invasion and metastasis of lung adenocarcinoma cells and may represent a potential biomarker and therapeutic target for lung cancer.

Design, modification and 3D QSAR studies of novel naphthalin-containing pyrazoline derivatives with/without thiourea skeleton as anticancer agents.

Two series of novel naphthalin-containing pyrazoline derivatives C1-C14 and D1-D14 have been synthesized and evaluated for their EGFR/HER-2 inhibitory and anti-proliferation activities. Compound D14 displayed the most potent activity against EGFR and A549 cell line (IC(50)=0.05 µM and GI(50)=0.11 µM), being comparable with the positive control Erlotinib (IC(50)=0.03 µM and GI(50)=0.03 µM) and more potent than our previous compounds C0-A (IC(50)=5.31 µM and GI(50)=33.47 µM) and C0-B (IC(50)=0.09 µM and GI(50)=0.34 µM). Meanwhile, compound C14 displayed the most potent activity against HER-2 and MCF-7 cell line (IC(50)=0.88 µM and GI(50)=0.35 µM), being a little less potent than Erlotinib (IC(50)=0.16 µM and GI(50)=0.08 µM) but far more potent than C0-A (IC(50)=6.58 µM and GI(50)=27.62 µM) and C0-B (IC(50)=2.77 µM and GI(50)=3.79 µM). The docking simulation was performed to analyze the probable binding models and the QSAR models were built for reasonable design of EGFR/HER-2 inhibitors at present and in future. The structural modification of introducing naphthalin moiety reinforced the combination of our compounds and the receptor, resulting in progress of bioactivity. Moreover, the replacement of thiourea skeleton by using benzene ring resulted in the slight diversity of the two series towards specific targets.

[Cardura monotherapy versus combination therapy of cardura and tolterodine L-tartrate tablets for II° ? benign prostatic hyperplasia with overactive bladder].

OBJECTIVE: To evaluate the effectiveness of the monotherapy of Cardura and the combination therapy of Cardura and Tolterodine L-Tartrate Tablets for II° ? benign prostate hyperplasia (BPH) with overactive bladder (OAB). METHODS: This study included 87 cases of BPH with OAB, with a disease course > or = 3 months, daily urination > or = 8 times, nocturnal urination > or = 2 times, urine volume < 200 ml per time, International Prostate Symptom Score (IPSS) > or = 8, OAB symptom score (OABS) > or = 3, quality of life score (QOL) > or = 3, post-void residual (PVR) < or = 100 ml, maximum urinary flow (Qmax) > or = 5 ml/s, prostate weight 25-50 g, and PSA < 4 microg/L. We randomized the patients to a monotherapy group (n = 44) and combination group (n = 43), the former treated with Cardura 4 mg qd, and the latter with Cardura 4 mg + Tolterodine L-Tartrate Tablets 4 mg qd, both for 8 weeks. Then we recorded the IPSS, OABS, Qmax, PVR, PSA, and adverse events. RESULTS: The baseline parameters showed no significant differences between the two groups (P > 0.05). In comparison with the baseline, both the monotherapy group and the combination therapy group showed significant decreased in the IPSS (16.50 +/- 4.27 vs 13.68 +/- 3.69 and 15.51 +/- 3.80 vs 11.49 +/- 2.75), urine storage symptom score (10.48 +/- 2.75 vs 7.98 +/- 2.34 and 9.47 +/- 2.31 vs 5.74 +/- 1.66), OABS (8.55 +/- 2.69 vs 6.32 +/- 1.97 and 8.21 +/- 2.55 vs 4.44 +/- 1.62), urgent micturition score (4.25 +/- 1.06 vs 3.23 +/- 0.99 and 4.07 +/- 0.83 vs 2.26 +/- 1.05), QOL (5.36 +/- 0.72 vs 3.43 +/- 0.66 and 5.07 +/- 0.86 vs 2.37 +/- 0.76) and PVR ([44.55 +/- 22.39] vs [38.30 +/- 20.20] ml and [36.19 +/- 21.21] vs [24.98 +/- 17.60] ml) (P < 0.01). All the six parameters were significantly more improved in the combination therapy group than in the monotherapy group (P < 0.01), but there were no remarkable differences between the groups in Qmax and voiding symptom score (P > 0.05). Neither group exhibited significant changes in the PSA level and prostate weight after treatment as compared with the baseline (P > 0.05). No acute urinary retention and other severe adverse reactions were observed during the medication. CONCLUSION: Both Cardura monotherapy and the combination therapy of Cardura + Tolterodine L-Tartrate Tablets can improve II ? BPH with OAB, and the latter has an even better efficacy than the former.

Identification of novel 3,5-diarylpyrazoline derivatives containing salicylamide moiety as potential anti-melanoma agents.

There is an accumulating body of experimental evidences validating oncogenic BRAF(V600E) as a therapeutic target and offering opportunities for anti-melanoma drug development. Encouraged by the positive results of pyrazole derivatives as BRAF(V600E) inhibitors, we sought to design diverse novel potential BRAF(V600E) inhibitors as antitumor agents based on pyrazole skeleton. In silico and in vitro screening of our designed pyrazole derivatives has identified Hit 1 as BRAF(V600E) inhibitor. Based on its structure and through further structure modification, compound 25, which exhibited the most potent inhibitory activity with an IC(50) value of 0.16 µM for BRAF(V600E) and GI(50) value of 0.24 µM for mutant BRAF-dependent melanoma cells, was obtained. The 3D-QSAR models and the molecular docking simulation were introduced to analyze the structure-activity relationship.

[Expression of transgelin-2 and clinical significance in colorectal cancer].

OBJECTIVES: To investigate the relationship between the expression of transgelin-2 and the clinicopathological factors of colorectal carcinoma and evaluate the value of transgelin-2 in prognostic assessment of the colorectal cancer patients. METHODS: Using tissue microarray and immunohistochemical methods, we examined transgelin-2 of 120 colorectal cancer patients received surgical treatment from September 2002 to April 2004, including 74 male and 46 female, age from 26 to 89 years. Analyzed the relationship between transgelin-2 and both the clinicopathological features and prognosis of the colorectal cancer by using χ² test and Kaplan-Meier survival analysis. Cox proportion hazard regression analysis was used to study the independent prognostic factors. RESULTS: The positive rate of transgelin-2 expression was 69.2% in colorectal carcinoma. The transgelin-2 expression correlated with differentiation degree (χ² = 5.420), lymph nodes metastasis (χ² = 45.577), distant metastasis (χ² = 12.009), and TNM staging (χ² = 47.577). The survival time was (39 ± 5) months in patients with positive expression of the transgelin-2, while (59 ± 3) months in patients with negative expression. The patient's survival time was statistically correlated with the transgelin-2 expression (P = 0.003). Distant metastasis (RR = 8.318, 95%CI: 4.119 - 16.790), lymph nodes metastasis (RR = 2.794, 95%CI: 1.246 - 6.263) and transgelin-2 expression (RR = 1.834, 95%CI: 1.118- 2.973) were independent prognostic factors in patients with colorectal cancer (P < 0.05). CONCLUSIONS: The expression of transgelin-2 is correlated with clinicopathological features and prognosis in colorectal cancer, may be the potential marker of metastasis and the prognosis of colorectal cancer patients.

Design, synthesis and biological evaluation of heterocyclic azoles derivatives containing pyrazine moiety as potential telomerase inhibitors.

Three series of novel heterocyclic azoles derivatives containing pyrazine (5a-5k, 8a-8k and 11a-11k) have been designed, synthesized, structurally determined, and their biological activities were evaluated as potential telomerase inhibitors. Among the oxadiazole derivatives, compound 5c showed the most potent biological activity against SW1116 cancer cell line (IC(50)=2.46 µM against SW1116 and IC(50)=3.55 µM for telomerase). Compound 8h performed the best in the thiadiazole derivatives (IC(50)=0.78 µM against HEPG2 and IC(50)=1.24 µM for telomerase), which was comparable to the positive control. While compound 11f showed the most potent biological activity (IC(50)=4.12 µM against SW1116 and IC(50)=15.03 µM for telomerase) among the triazole derivatives. Docking simulation by positioning compounds 5c, 8h and 11f into the telomerase structure active site was performed to explore the possible binding model. The results of apoptosis demonstrated that compound 8h possessed good antitumor activity against HEPG2 cancer cell line. Therefore, compound 8h with potent inhibitory activity in tumor growth inhibition may be a potential antitumor agent against HEPG2 cancer cell. Therefore, the introduction of oxadiazole, thiadiazole and triazole structures reinforced the combination of our compounds and the receptor, resulting in progress of bioactivity.

Design, modification and 3D QSAR studies of novel 2,3-dihydrobenzo[b][1,4]dioxin-containing 4,5-dihydro-1H-pyrazole derivatives as inhibitors of B-Raf kinase.

Two series of novel 2,3-dihydrobenzo[b][1,4]dioxin-containing 4,5-dihydro-1H-pyrazole derivatives C1-C15 and D1-D15 have been synthesized and evaluated for their B-Raf inhibitory and anti-proliferation activities. Compound C14 ((3-(4-bromophenyl)-5-(2-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanone) showed the most potent biological activity against B-Raf(V600E) (IC(50) = 0.11 µM) and WM266.4 human melanoma cell line (GI(50) = 0.58 µM), being comparable with the positive control Erlotinib and more potent than our previous best compound, while D10 ((2,3-dihydrobenzo[b][1,4]dioxin-2-yl)(5-(3-fluorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)methanone) performed the best in the D series (IC(50) = 1.70 µM; GI(50) = 1.45 µM). The docking simulation was performed to analyze the probable binding models and poses and the QSAR model was built for reasonable design of B-Raf inhibitors in future. The introduction of 2,3-dihydrobenzo[b][1,4]dioxin structure reinforced the combination of our compounds and the receptor, resulting in progress of bioactivity.

Design, synthesis, biological evaluation and molecular modeling of novel 1,3,4-oxadiazole derivatives based on Vanillic acid as potential immunosuppressive agents.

In present study, a series of novel 1,3,4-oxadiazole derivatives have been designed, synthesized and purified. All of these compounds are reported for the first time, the chemical structures of these compounds were confirmed by means of (1)H NMR, ESI-MS and elemental analyses. Besides, we evaluated their immunosuppressive activity. Most of these synthesized compounds were proved to have potent immunosuppressive activity and low toxicity. Among them, the bioassay results demonstrated that compounds 5c, 5n, 5p, 5o, 6f and 6g exhibited immunosuppressive activities with IC(50) concentration range from 1.25µM to 7.60 µM against the T cells, and the IC(50) of positive control (csa) is 2.12 µM. Moreover, all the title compounds were assayed for PI3K/AKT signaling pathway inhibition using the ELISA assay. We examined the compounds with potent inhibitory activities against IL-1, IL-6 and IL-10 released in ConA-simulated mouse lymph node cells. The results showed compounds 5o and 6f displayed the most potential biological activity against T cells (IC(50)=1.25 µM and 4.75 µM for T cells). The preliminary mechanism of compound 5o inhibition effects was also detected by flow cytometry (FCM). The results of apoptosis and ELISA assay demonstrated that the immunosuppressive activity of compounds 5o and 6f against T cells may be mediated by the inhibition of PI3Kγ/AKT signaling pathway. Molecular docking was performed to position compounds 5o and 6f into PI3Kγ binding site in order to indicate the potential target.

Salvianolic acid A inhibits angiotensin II-induced proliferation of human umbilical vein endothelial cells by attenuating the production of ROS.

AIM: To investigate the action of salvianolic acid A (SalA) on angiotensin II (Ang II)-induced proliferation of human umbilical vein endothelial cells (HUVECs) and the possible signaling pathways mediating this action. METHODS: Cell proliferation was examined with MTT assay. The expression levels of Src phosphorylation (phospho-Src), Akt phosphorylation (phospho-Akt), and NADPH oxidase 4 (Nox4) in HUVECs were determined by Western blot. The production of reactive oxygen species (ROS) was estimated using fluorescence-activated cell sorting (FACS). RESULTS: SalA (6.25-50 µmol/L) did not affect the viability of HUVECs. Treatment of HUVECs with Ang II (1 µmol/L) markedly increased the cell viability; pretreatment of HUVECs with SalA (12.5, 25 and 50 µmol/L) prevented Ang II-induced increase of the cell viability in a concentration-dependent manner. Treatment of HUVECs with Ang II (1 µmol/L) markedly up-regulated the protein expression levels of phospho-Src, phospho-Akt (473) and Nox4; pretreatment of HUVECs with SalA (12.5, 25 and 50 µmol/L) blocked all the effects in a concentration-dependent manner. Treatment of HUVECs with Ang II (1 µmol/L) dramatically increased ROS production in HUVECs; pretreatment of HUVECs with SalA (12.5, 25 and 50 µmol/L) blocked the ROS production in a concentration-dependent manner. CONCLUSION: SalA inhibits Ang II-induced proliferation of HUVECs via reducing the expression levels of phospho-Src and phospho-Akt (473), thereby attenuating the production of ROS.

Synthesis, biological evaluation, and molecular docking studies of 1,3,4-oxadiazole derivatives possessing 1,4-benzodioxan moiety as potential anticancer agents.

In present study, a series of new 1,3,4-oxadiazole derivatives containing 1,4-benzodioxan moiety (6a-6s) as potential telomerase inhibitors were synthesized. The bioassay tests demonstrated that compounds 6k, 6l, 6m, 6n and 6s exhibited broad-spectrum antitumor activity with IC(50) concentration range from 7.21 µM to 25.87 µM against the four cancer cell lines, HEPG2, HELA, SW1116 and BGC823. Moreover, all the title compounds were assayed for telomerase inhibition using the TRAP-PCR-ELISA assay. The results showed compound 6k possessed the most potent telomerase activity (IC(50)=1.27 ± 0.05 µM). Docking simulation was performed to position compound 6k into the active site of telomerase (3DU6) to determine the probable binding model.