Search

Cancer cells can enter quiescent or dormant state to resist anticancer agents while maintaining the potential of reactivation. However, the molecular mechanism underlying quiescence entry and reactivation remains largely unknown. In this paper, cancer cells eventually entered a reversible quiescent state to resist long-term paclitaxel (PTX) stress. The quiescent cells were characterized with Na+/H+ exchanger 1 (NHE1) downregulation and showed acidic intracellular pH (pHi). Accordingly, decreasing pHi by NHE1 inhibitor could induce cell enter quiescence. Further, acidic pHi could activate the ubiquitin-proteasome system and inhibiting proteasome activity by MG132 prevented cells entering quiescence. In addition, we show that after partial release, the key G1-S transcription factor E2F1 protein level was not recovered, while MCM7 protein returned to normal level in the reactivated cells. More importantly, MCM7 knockdown inhibited G1/S genes transcription and inhibited the reactivated proliferation. Taken together, this study demonstrates a regulatory function of intracellular acidification and subsequent protein ubiquitination on quiescence entry, and reveals a supportive effect of MCM7 on the quiescence-reactivated proliferation.

Immune/stromal-associated genes may be promising biomarkers for cancer diagnosis and the determination of clinical cancer treatment options. The aim of the present study was to identify prognostic stromal/immune-associated genes in renal cell carcinoma (RCC). RCC gene expression data (885 cases) were obtained from The Cancer Genome Atlas database. Immune/stromal scores were calculated by using the ESTIMATE package in R. Immune/stromal scores were significantly associated with Tumor-Node-Metastasis stage, clinical stage and overall survival rate (P

Objective To evaluate the differences in the clinical effect and the safety in the treatment of post-stroke anxiety disorder (PSAD) between electroacupuncture (EA) and paroxetine on the base of the heart-brain theory. Methods A total of 70 patients of PSAD were randomized into an EA group and a medication group, 35 cases in each one. In the EA group, four acupoints were selected and divided into two pairs. In the Pair A, there were Baihui (百会 GV20) and Fēngfŭ (风府 GV16). In the Pair B, there were Xīnshū (心俞 BL15) and Shenmen (神门 HT7). After acupuncture, the electroacupuncture apparatus was applied. The duration of needle retention was 20 min. EA was given three times a week, totally for 4 weeks. In the medication group, paroxetine tablets were administered orally, 10 mg daily in the first 4 days and 20 mg afterwards, totally for 4 weeks. Before and after treatment, as well as in the follow-up period, Hamilton anxiety scale (HAMA), Barthel index (BI) for daily life ability, and clinical global impression (CGI) were observed and the clinical therapeutic effect was evaluated separately. Results A total of 3 cases were dropped-out in the medication group. Finally, 35 cases in the EA group and 32 cases in the medication group were included in the analysis. Compared with the scores before treatment, the scores of HAMA and CGI-SI (severity of illness) were lower and the scores of BI were higher after treatment and during the follow-up in either the EA group or the medication group (all P 0.05). Compared with the medication group, BI score in the EA group was higher in the follow-up, indicating the statistical significance (P Conclusions The therapeutic effect of electroacupuncture on the base of heart-brain theory is similar to the oral administration of paroxetine in the treatment of post-stroke anxiety disorder. This therapy relieves anxious emotions, promotes the recovery of limb function and has less adverse reactions in the patients.

Introduction: Cancer stem cells (CSCs) are the main source of tumor resistance and recurrence. At present, the main treatment for patients with advanced or metastatic bladder cancer (BCa) is cisplatin-based combination chemotherapy. However, CSCs are not sensitive to DNA-damaging drugs due to their enhanced DNA damage response (DDR) activity. Materials and methods: Bladder cancer stem cell-like cells (BCSLCs) were obtained by treating UMUC3 cells with cisplatin. The characteristics of the BCSLCs were identified by qPCR, flow cytometry, scratch wound-healing assays, transwell assays, tumorigenic ability experiments, Edu assays and Western blot assays in vivo. After BCSLCs were treated with norcantharidin (NCTD), the expression of Cdc6 and activation of the ATR-Chk1 pathway were detected by Western blotting. A subcutaneous tumor model in nude mice was successfully established to assess the anti-tumor efficacy of NCTD and cisplatin either alone or in combination in vivo. The tumor tissues were detected by immunohistochemistry. Results: The derived BCSLCs showed higher expression of stemness markers, increased invasiveness, improved resistance to multiple chemotherapeutics, and higher tumorigenic capacity in vivo. The protein expression level of chromatin-binding Cdc6 was increased in BCSLCs; however, NCTD decreased the level of chromatin-binding Cdc6 and inhibited the activation of the ATR-Chk1 pathway, which ultimately led to reduction in DDR activity in BCSLCs. NCTD enhanced the killing effect of cisplatin on BCSLCs in vitro and vivo. NCTD combined with cisplatin enhanced cisplatin-induced DNA damage in BCSLCs. Conclusion: Long-term cisplatin treatment can enrich BCSLCs. However, NCTD enhanced the killing effect of cisplatin on BCSLCs in vitro and vivo. The mechanism is inhibiting the DDR activity by reducing the expression of chromatin-binding Cdc6.

Objective To observe the clinical efficacy of acupuncture on back-shu points of five zang in treating chronic fatigue syndrome (CFS). Methods Sixty patients were randomized into treatment group and control group. In treatment group, the back-shu points of five zang organs were adopted for acupuncture. Shenshū (肾俞 BL23) was perpendicularly needled 15–30 mm in depth. The rest of the selected points were inserted obliquely 15–30 mm in the direction of the spine with even method of lifting-thrusting and twisting-twirling, 10 s for each acupoint. In control group, the acupoints were approximately 1.5–2 cm away outward from the back-shu points of five zang organs (about on the middle of the two sidelines of the bladder meridian of foot-taiyang) and the points from the bladder meridian of foot-taiyang were excluded. Acupoints were needled 6–9 mm in depth, and deqi was not required, without any manipulation. The treatments were carried out twice a week for twenty minutes each time, a total of eight treatments were given. The clinical efficacy of acupuncture treatment for CFS was evaluated through the Fatigue Scale-14 (FS-14) and the Symptom Check-List 90 (SCL-90) after treatment. Results The total effective rate was 86.67% in the treatment group and 53.33% in the control group (P Conclusions Acupuncture on back-shu points of five zang can significantly improve the somatic fatigue and mental fatigue of the patients, and at the same time improve their psychological status. Significant therapeutic effect was found on CFS. Compared with the control group, the acupuncture treatment can significantly improve the patient's somatic fatigue, mental fatigue and psychological status.

Background: Evidence for treating postprandial distress syndrome with acupuncture is limited. Aim: We aimed to evaluate the feasibility of verum acupuncture versus sham acupuncture in patients with postprandial distress syndrome. Methods: A total of 42 eligible patients were randomly allocated to either verum acupuncture or sham acupuncture groups in a 1:1 ratio. Each patient received 12 sessions over 4 weeks. The primary outcome was the response rate based on the overall treatment effect (OTE) 4 weeks after randomization. Secondary outcomes included dyspepsia symptom severity and adverse events. Results: In each group, 19 patients (91.5%) completed the study. Thirteen patients receiving verum acupuncture and seven patients receiving sham acupuncture were classified as responders according to OTE (61.9% vs 33.3%; rate difference 28.6%; p = 0.06). Dyspepsia symptom severity at the end of treatment also differed significantly between verum acupuncture and sham acupuncture groups (5.9 units vs 3.7 units; between-group difference 2.2 (95% CI, 0.2–4.2); p = 0.04). No serious adverse events occurred. Conclusion: Four weeks of acupuncture may represent a potential treatment for postprandial distress syndrome. The treatment protocol and outcome measures used in this trial were feasible. Since this was a pilot study, the efficacy of acupuncture still needs to be determined by a larger, adequately powered trial.

Supplemental material, supplementary_Table_1 for Acupuncture for postprandial distress syndrome: a randomized controlled pilot trial by Jian-Feng Tu, Jing-Wen Yang, Li-Qiong Wang, Yang Zheng, Li-Wen Zhang, Yong-Ting Li, Xin Zhang, Guang-Xia Shi, Jun Wang, Jing-Jie Zhao, Yi Du, San-San Chen, Lu Cheng and Cun-Zhi Liu in Acupuncture in Medicine

BACKGROUND The aim of this study was to investigate the benefit of nephron sparing surgery (NSS) compared with extirpative nephrectomy in different tumor stages of renal cell carcinoma. MATERIAL AND METHODS We reviewed the Surveillance, Epidemiology and End Results (SEER) database for NSS and extirpative nephrectomy in localized (stages T1-2N0M0) renal cell carcinoma diagnosed after 2004. We used the variable screening function of the SEER database to identified 55,947 cases that met inclusion and exclusion criteria for survival analysis. Overall mortality and cancer-specific mortality were the primary index outcomes. Stratification analysis was done by T stage subgroups. We also performed survival analysis using propensity score analysis, and changed the survival model to the competing-risk model for cancer-specific mortality analysis. RESULTS Overall, NSS significantly decreased the risk of overall mortality (HR 0.717, 0.668-0.769) and cancer-specific mortality (HR 0.604, 0.525-0.694) when compared to extirpative nephrectomy. In subgroup analysis, NSS had a lower overall mortality risk and cancer-specific mortality compared to extirpative nephrectomy only for T1a stage renal cell carcinoma (HR 0.654, 0.599-0.714, p

Background Postprandial distress syndrome (PDS) is referred to as meal-related functional dyspepsia (FD) and causes a reduced quality of life (QoL) for patients. Several randomized controlled trials (RCTs) have suggested that acupuncture is an effective treatment for FD, but few studies were particularly for PDS. This pilot study was designed to determine the feasibility and efficacy of acupuncture in patients with PDS characterized by postprandial fullness and early satiation according to the Rome III criteria. Methods This is a multi-center, two-arm, blinded (participants), pilot RCT. Forty-two participants who meet the inclusion criteria will be randomly assigned to the verum acupuncture group or minimal acupuncture group in a 1:1 ratio. Both treatments consist of 12 sessions of 20 min duration over four weeks (three sessions per week). The primary outcome measurement is the proportion of persons who improve as assessed using the global outcome by the overall treatment effect (OTE) at end-of-treatment (EOT) (four weeks after randomization). Global assessment at weeks 8 and 16 after randomization is one of the secondary outcomes. The other secondary outcomes including symptoms, disease-specific QoL, and depression and anxiety will be assessed at weeks 4, 8, and 16 after randomization. Discussion This pilot study will help determine the feasibility and efficacy of acupuncture in patients with PDS. Trial registration ISRCTN Registry, ISRCTN18135146. Registered on 7 July 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2285-9) contains supplementary material, which is available to authorized users.

Sen Wang, Wei-Cheng Gao, San-San Chen, Liang Bai, Li Luo, Xiang-Guang Zheng, You Luo Department of Urology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China Objective: To define the survival effect of surgery of primary adrenal malignant lesions in metastatic adrenocortical carcinoma (ACC) patients. Patients and methods: We used the Surveillance, Epidemiology and End Results (SEER) database (1973–2014) to identify metastatic ACC patients (stage IV by using European Network for the Study of Adrenal Tumors stage classification). Correlated variables, including age, sex, race, tumor laterality, treatment modality, lymph node dissection, surgery of metastatic site, tumor size, and tumor stage, were extracted. Univariate and multivariate Cox regression analyses were used to define the efficacy of surgery on survival outcomes, including overall survival and cancer-specific survival of ACC. Results: There were 290 metastatic ACC patients identified from the database. The overall median survival time was 7 (95% CI, 6–8) months. Among these patients, 118 patients received primary site surgery and 172 patients did not. In both univariate and multivariate analyses, primary site surgery significantly improved both overall (hazard ratio 0.413, 95% CI, 0.299–0.571, P

Adrenocortical carcinoma (ACC) is a rare and malignant tumor. The main treatment is primary surgical resection with or without mitotane therapy. The role of radiation therapy is still controversial. We aim to investigate the survival efficacy of radiotherapy in a large population-based cohort. We queried the Surveillance, Epidemiology, and End Results (SEER) database (1973–2013) to identify cases with ACC. Traditional multivariate Cox regression and propensity score analysis were used to evaluate the effect of radiotherapy on cancer survival. The survival outcomes included overall survival and cancer-specific survival. The treatment effect was evaluated using a hazard ratio (HR) and its 95% confidence interval (95% CI). Five hundred thirty patients diagnosed with ACC were identified. Among them, 74 patients received radiotherapy. In the multivariate Cox regression, radiotherapy did not increase the overall survival (HR 0.794, 95% CI 0.550–1.146, P = .218) or cancer-specific survival (HR 0.842, 95% CI 0.574–1.236, P = .388). In the propensity score analysis, the results consistently showed no survival benefit of radiotherapy regardless of the different propensity score analysis methods. Radiotherapy did not improve overall or cancer-specific survival in ACC patients. Further confirmation is needed from multi-institutional prospective studies in the future.

SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents.* (PDF 192Â kb)

Trial registration: Acupuncture for postprandial distress syndrome (PDS). (PDF 23Â kb)

To construct a recombinant lentiviral vector for p38 MAPK and establish a human prostatic carcinoma cell line that stably expresses p38 MAPK.EGFP/p38 fusion gene was subcloned into the lentiviral vector pTYF- EF1α-IRES-EGFP. The recombinant lentiviral vector pTYF-EF1α-EGFP/p38 was indentified by restriction enzyme digestion, and packaged in HEK 293T cells using lipofectamintm2000 with the packaging plasmid psPAX2 and envelope plasmid pMD2.G. The viral titer was tested according to the expression level of GFP. The resulting recombinant lentiviral vector was transduced into human prostatic carcinoma DU145 cells, and stably transduced cells were selected by limiting dilution analysis. The intracellular expression level of total p38 was detected by Western blotting and the cell growth curve was drawn.DNA restriction enzyme digestion demonstrated that the recombinant lentiviral vector of the fusion gene EGFP/p38 (pTYF-EF1α-EGFP/p38) was constructed successfully. The recombinant lentiviral vector was packaged in 293T with a viral titer of 4.7×10(6) TU/ml. A stable cell line, EGFP/p38-DU145, was established, which stably expressed exogenous EGFP/p38 MAPK fusion protein as detected by Western blotting and showed a lowered growth rate compared to the control cells.We have successfully constructed a recombinant lentiviral vector of the fusion gene EGFP/p38 and established a stable cell line EGFP/p38-DU145. Overexpression of p38 has a significant inhibitory effect on the proliferation of DU145 cells in vitro.

During cyclic voltammetry the ferrous complex Fe(PDT) 3 2+ is both reduced and oxidized on a GCE in acetonitrile solvent. The reduction occurs in three steps, while during its oxidation, the Fe(III) species is generated at a more positive potential than the standard potential of the simple Fe(III)/Fe(II) couple. The anodic peak potential promises to be useful as a reference for measurements in non-aqueous solvents. The diffusion coefficient of the species in acetonitrile is reported.