Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase Ⅱ trial

Objective:Glioblastomas are highly vascularized malignant tumors.We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor,anlotinib,for a newly diagnosed glioblastoma.Methods:This multicenter,single-arm trial(NCT04119674)enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November 2020.Patients underwent treatment with the standard STUPP regimen[fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w×6 w(total=54-60 Gy)]or radiotherapy plus continuous daily temozolomide(TMZ)(75 mg/m^(2)of body surface area/d,7 d/w from the first to the last day of radiotherapy),followed by 6 cycles of adjuvant TMZ(150-200 mg/m^(2)×5 d during each 28-d cycle)plus anlotinib(8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy,8 maximal cycles as adjuvant therapy,followed by maintenance at 8 mg/d.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival(OS)and adverse events(AEs).Results:Thirty-three patients received the planned treatment.The median PFS was 10.9 months(95%CI,9.9-18.7 months)and the 12-month PFS rate was 48.5%.The median OS was 17.4 months(95%CI,14.5-21.1 months)and the 12-month OS rate was 81.8%.The most common AEs included hypertriglyceridemia[58%(n=19)],hypoalbuminemia[46%(n=15)],and hypercholesterolemia[46%(n=15)]during concurrent chemoradiotherapy and leukopenia[73%(n=24)],hypertriglyceridemia[67%(n=22)],and neutropenia[52%(n=17)]during adjuvant therapy.Five patients discontinued treatment due to AEs.HEG1(HR,5.6;95%CI,1.3-23.7;P=0.021)and RP1L1 alterations(HR,11.1;95%CI,2.2-57.2;P=0.004)were associated with a significantly shorter PFS.Conclusions:Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity.HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

EZH2 is a biomarker associated with lung cancer diagnosis and immune infiltrates without prognostic specificity: a study based on the cancer genome atlas data

Enhancer of zeste homolog 2(EZH2)is the catalytic subunit of polycomb repressive complex 2(PRC2).Dysregulation of EZH2 causes alteration of gene expression and functions,thereby promoting cancer development.Recent studies suggest that EZH2 has a potential prognostic role in patients with nonsmall cell lung cancer(NSCLC).However,the prognostic value of EZH2 expression levels in NSCLC is controversial.In this study,we evaluated the prognostic value in lung cancer(LC-LUAD/LUSC)based on data from The Cancer Genome Atlas(TCGA)database.Kruskal-Wallis test,Wilcoxon signed-rank test,and logistic regression were used to evaluate the relationship between EZH2 expression and clinicopathological features.Cox regression and the Kaplan-Meier method were adopted to evaluate prognosis-related factors.Gene set enrichment analysis(GSEA)was performed to identify the key pathways related to EZH2.The correlations between EZH2 and cancer immune infiltrates were investigated by single-sample Gene Set Enrichment Analysis(ssGSEA).EZH2 was found to be up regulated with amplification in tumor tissues in multiple LC cohorts.High EZH2 expression was associated with poorer overall survival(OS).GSEA suggested that EZH2 regulates innate immune system,ECM affiliated,matrisome,surfactant metabolism.Notably,ssGSEA indicated that EZH2 expression was positively correlated with infiltrating levels of Th2 cells and significantly negatively correlated with mast cell infiltration level.These results suggest that EZH2 is associated with LC immune infiltration and significantly over-expressed in lung cancer,and its diagnostic value is better than prognosis,which lays a foundation for further study of the immunomodulatory role of EZH2 in LC.

The Relationship between p38MAPK and Apoptosis during Paclitaxel Resistance of Ovarian Cancer Cells

To investigate the relationship between p38 mitogen-activated protein kinase （p38MAPK） and cell apoptosis during the paclitaxel resistance of ovarian carcinoma cell lines, flow cytometry （FCM） and PI staining were employed to determine the effect of p38MAPK inhibitor SB203580 on the apoptosis of A2780/Taxol cells, a drug-resistant human ovarian carcinoma cell line. p38MAPK protein expression in SB203580-treated cells was immunochemically measured. The 50% inhibition concentration （IC50） of paclitaxel on A2780/Taxol cells was determined by MTT assay. MDR-1 mRNA, and expression of p38MAPK and phospho-p53 protein were detected by RToPCR and Western blotting, respectively. The apoptosis rate of A2780/Taxol cells was （19.7±1.04）% 24 h after SB203580 treatment. A significant difference in apoptosis rate was found among experiment group, control group and untreated group （p〈0.05）. The relative reversal rate of A2780/Taxol cells to paclitaxel was （57.18±2.01）%. As compared with the control group and the untreated group, p38MAPK protein and MDR-1 mRNA in SB203580-treated cells was substantially decreased. The expression of p53 protein was significantly increased. It is concluded that p38MAPK pathway is related to paclitaxel resistance of ovarian carcinoma, and blockade of this pathway can promote the apoptosis of the drug-resistant cells and reverse the drug-resistance. Moreover, p38MAPK-mediated apoptosis in paclitaxel-resistant ovarian carcinoma cells depends on the activation of p53.

Research on the effect of health care integration on patients’ negative emotions and satisfaction with lung cancer nursing activities

BACKGROUND Lung cancer is a clinical disease with multiple malignant tumors.Currently,it is difficult for patients to benefit from routine clinical nursing due to the lack of a pertinent and systematic approach.AIM To investigate the effect of integrated nursing care on the negative emotions and satisfaction of lung cancer patients.METHODS From January 2018 to December 2019,92 patients with lung cancer were selected and divided into the study group and the control group;there were 46 patients in each group.The control group received routine nursing,and the study group received integrated medical care in addition to the care received by the control group.Negative emotions before and after the intervention,the self-management ability score after the intervention,family care burden after the intervention and nursing satisfaction after the intervention were measured in the two groups.RESULTS After the intervention,the self-rating anxiety scale and self-rating depression scale scores in the study group were lower than those in the control group(P<0.05);the scores for health knowledge,self-concept,self-responsibility and self-care skills in the study group were higher than those in the control group(P<0.05);the scores for individual burden and responsibility burden in the study group were lower than those before the intervention(P<0.05);and the nursing satisfaction in the study group(93.48%)was higher than that in the control group(78.26%,P<0.05).CONCLUSION An integrated nursing care approach for lung cancer patients can effectively relieve the patient’s negative feelings,improve their self-management ability,help to reduce the burden of family care and improve patient satisfaction with nursing activities.

The diverse and contrasting effects of using human prostate cancer cell lines to study androgen receptor roles in prostate cancer

The androgen receptor （AR） plays an important role in the development and progression of prostate cancer （PCa）. Androgen deprivation therapy is initially effective in blocking tumor growth, but it eventually leads to the hormonerefractory state. The detailed mechanisms of the conversion from androgen dependence to androgen independence remain unclear. Several PCa cell lines were established to study the role of AR in PCa, but the results were often inconsistent or contrasting in different cell lines, or in the same cell line grown under different conditions. The cellular and molecular alteration of epithelial cells and their microenvironments are complicated, and it is difficult to use a single cell line to address this important issue and also to study the pathophysiological effects of AR. In this paper, we summarize the different effects of AR on multiple cell lines and show the disadvantages of using a single human PCa cell line to study AR effects on PCa. We also discuss the advantages of widely used epithelium-stroma co-culture systems, xenograft mouse models, and genetically engineered PCa mouse models. The combination of in vitro cell line studies and in vivo mouse models might lead to more credible results and better strategies for the study of AR roles in PCa.

Assessment of Monitor Units and Gamma Pass Rate for 6 MV and Flattening Filter Free (FFF) Beams in Volumetric Modulated Arc Therapy (VMAT)

Background: In linear accelerators, the treatment field’s uniform intensity is achieved by including a flattening filter in the beam. However, to produce more conformal dose distributions, contemporary radiotherapy practice now frequently uses fluence and aperture modifying techniques, such as volumetric modulated arc therapy. In these circumstances, the flattening filter in the beam manufacturing process is no longer required. It is therefore necessary to compare the monitor units of 6 MV and flattening filter free plans and how it influences the gamma pass rates to determine which is best for treating cervical cancer with pelvic lymph node metastasis. Methods: VMAT plans for fifteen patients with cervical cancer with pathological pelvic lymph node metastasis were included in this study. Each patient had two VMAT plans using conventional 6 MV beam with flattening filter and one with flattening filter free beam (FFF). The VMAT plans were made using two arcs, and then recalculated to give the planned dose distribution to the detectors in a Delta4 phantom. The VMAT plans were irradiated on the Delta4 phantom using an Elekta linear accelerator (6 MV). Results: The mean monitor unit for the 6 MV plans was 506.3 MU and a standard deviation of 48.6 while that of the FFF plans had a mean MU of 701.5 with a standard deviation of 87.6. The total monitor units (MUs) for the FFF plans were significantly greater than the 6 MV plans (p = 6.1 × 10-5). Conclusion: Flattening filter free (FFF) plans require more numbers of monitor units in comparison to conventional 6 MV filtered beams for external radiation of cervical cancer with pelvic lymph nodes involvement.

Gallbladder carcinosarcoma with a poor prognosis: A case report

BACKGROUND Carcinosarcoma of the gallbladder is a rare malignant tumor with a very poor prognosis.To date,only approximately 100 patients have been reported in the English literature.The prognosis of this tumor type is poor,the preoperative diagnosis is difficult,and there is a possibility of a misdiagnosis.We present an unsuccessful case of carcinosarcoma of the gallbladder with a preoperative misdiagnosis and rapid early postoperative recurrence.Therefore,we have a deeper understanding of the poor prognosis of gallbladder carcinosarcoma(GBC)patients.CASE SUMMARY The patient is a 65-year-old male.He was admitted to the hospital because of right upper abdomen distending pain and discomfort for half a month.Abdominal magnetic resonance imaging revealed a polycystic mass in the right lobe of the liver and the fossa of the gallbladder.After admission,the patient was diagnosed with a liver abscess,which was treated by abscess puncture drainage.Obviously,this treatment was unsuccessful.Hepatectomy and cholecystectomy were performed one month after the puncture.Postoperative pathologic examination revealed carcinosarcoma of the gallbladder,and the resected specimen contained two tumor components.One month after surgery,the patient's tumor recurred in situ and started to compress the duodenum,resulting in duodenal obstruction and bleeding.The treatment was not effective.The patient died of gastrointestinal hemorrhage and hypovolemic shock.CONCLUSION Carcinosarcoma of the gallbladder is a rare malignant tumor that is easily misdiagnosed preoperatively and has a poor prognosis.

Expression of human AR cDNA driven by its own promoter results in mild promotion, but not suppression, of growth in human prostate cancer PC-3 cells

Aim： To examine the physiological role of the androgen receptor （AR） in the PC-3 cell line by transfecting full-length functional AR cDNA driven by its natural human AR promoter. Methods： We generated an AR-expressing PC-3（AR）9 stable clone that expresses AR under the control of the natural human AR promoter and compared its proliferation to that of the PC-3（AR）2 （stable clone that expresses AR under the control of the cytomegalovirus （CMV） promoter, established by Heisler et al.） after androgen treatment. Results： We found that dihydrotestosterone （DHT） from 0.001 nmol/L to 10 nmol/L induces cell cycle arrest or inhibits proliferation of PC-3（AR）2 compared with its vector control, PC-3（plRES）. In contrast, PC-3（AR）9 cell growth slightly increased or did not change when treated with physiological concentrations of 1 nmol/L DHT. Conclusion： These data suggest that intracellular control of AR expression levels through the natural AR promoter might be needed for determining AR function in androgen-independent prostate cancer （AIPC） PC-3 cells. Unlike previous publications that showed DHT mediated suppression of PC-3 growth after transfection of viral promoter-driven AR overexpression, we report here that DHT-mediated PC-3 proliferation is slightly induced or does not change compared with its baseline after reintroducing AR expression driven by its own natural promoter, as shown in PC-3（AR）9 prostate cancer cells.

Id2 regulates the proliferation of squamous cell carcinoma in vitro via the NF-κB/Cyclin D1 pathway

Squamous cell carcinoma (SCC) is a significant cause of cancer morbidity and mortality worldwide, with an incidence of up to 166 cases per 100 000 population. It arises in the skin, upper aerodigestive tract, lung, and cervix and affects more than 200 000 Americans each year. We report here that a microarray experiment comparing 41 SCC and 13 normal tissue specimens showed that Id2, a gene that controls the cell cycle, was significantly up-regulated in SCC. Enforced expression of Id2 in vitro stimulated the proliferation of SCC cells and up-regulated the transcription of nuclear factor kappa B (NF-κB) and cyclin D1. Enhancement of the NF-κB activity with p65 significantly increased the cell proliferation and the transcription of cyclin D1, whereas inhibition of the NF-κB activity with I kappa B alpha mutant (IκBα M) and pyrroline dithiocarbamate (PDTC) abrogated cell proliferation and transcription of cyclin D1. Furthermore, a mutated NF-κB binding site in the cyclin D1 promoter fully abrogated the Id2-induced transcription of cyclin D1. Taken together, these data indicate that Id2 induces SCC tumor growth and proliferation through the NF-κB/cyclin D1 pathway.

Generation of iPS cells using defined factors linked via the self-cleaving 2A sequences in a single open reading frame

导致的 pluripotent 的产生从体的细胞的茎(iPS ) 细胞被定义 reprogramming 抄写因素(TF ) 的同时的病毒的 transduction 成功地完成了。然而，这个过程为基因交货要求多重病毒的向量。作为结果，产生了 iPS 房间港口在他们的染色体的众多的病毒的集成地点。这能增加基因 mutagenesis 和 genomic 不稳定性的概率，并且介绍重要障碍给研究和 iPS 房间的临床的申请研究。在这篇论文，我们在场定义因素是的一个简单 lentivirus reprogramming 在系统经由自我劈开的 2A 序列熔化了在里面框架进一个单个开的读物框架(ORF ) 。一个 GFP 标记下游地被放 transgene 启用 transgene 表示追踪。我们证明这个 polycistronic 表示系统高效地产生 iPS 房间。产生 iPS 房间有正常 karyotypes 并且类似于鼠标在形态学和基因表示的胚胎的干细胞。而且，他们能在 vitro 并且在 vivo 试金在两个区分进三胚胎的细菌层的房间类型。显著地，大多数这些 iPS 房间仅仅怀有病毒的向量的一个单个拷贝。这个系统提供一个珍贵工具因为 iPS 房间的产生，和我们的数据建议在每个房间的 transduced reprogramming TF 的表示的平衡为 reprogramming 进程是必要的。更重要地，当由非集成的基因交货系统交付了时，这重新设计的单个 ORF 将没有基因修正便于人的 iPS 房间的有效产生。

The Expression Levels of Endogenous aFGF mRNA in Microwave Burn Wound Tissues and Its Clinical Significance

The expression levels and changes of endogenous acid fibroblast growth factor （aFGF） in microwave burn wound tissues were detected in order to investigate how to get better therapeutic effects by using the exogenous aFGF for repairing trauma. A burnt-wound animal model was established by NS-FⅡ multifunction spectrum therapeutics equipment, and reverse transcriptase-polymerase chain reaction （RT-PCR） and immunohistochemistry assay were applied to detect the expression levels of endogenous aFGF mRNA in microwave burn wound tissues. The expression level of endogenous aFGF mRNA was significantly increased in the burn wound tissues 12 h after burn, reached the peak at 48 h, and gradually deceased 96 h after burn. The expression of endogenous aFGF mRNA after tissue damage was reversible, and its intensity was in accordance with the repair process of tissue damage, suggesting endogenous aFGF may take part in the cell metabolism and proliferation, and then promote the repair of the burn wound.

Primary malignant melanoma of the esophagus successfully treated with camrelizumab:A case report and literature review

An 83-year-old Chinese woman presented with a 3-month history of dysphagia.She also had a history of hypertension,type 2 diabetes,fundus hemorrhage,and cataract but no history of cutaneous,ocular,or other-site melanomas.Upper gastrointestinal tract angiography revealed gastritis and duodenal diverticulum;thus,an endoscopic review was recommended.Enhanced computed tomography of the chest and upper abdomen revealed the following:(1)Esophageal space-occupying lesions and mediastinal lymph node enlargement(considering the high possibility of esophageal cancer,further endoscopy was recommended)and(2)A small amount of right pleural effusion,with no significant lymph node infiltration or distant metastasis.Esophagoscopy identified a bulge mass blocking the esophagus from 23 to 30 cm from the incisors.The upper mass had a spherical clustering,while the lower mass significantly festered.Pathological biopsy samples were obtained from the esophagus 23 and 28 cm from the incisors.Tissue biopsy showed proliferation of large round tumor cells and melanocytes.Immunohistochemistry showed positive findings for HMB45 and MelanA;partially positive findings for S100,CK7,CK5/6,CAM5.2,LCA,P63,and TTF-1;and negative findings for Syn.The Ki-67 positivity index was approximately 60%.Based on these findings,the patient was diagnosed with malignant esophageal melanoma with enlarged mediastinal lymph nodes.She was then treated with five cycles of camrelizumab therapy combined with chemotherapy from October 18,2019,to May 5,2020.Gastroscopy review following two courses of combination therapy revealed that the esophagus was 23-25 cm away from the incisors,and there were two continuous uplifted and beaded masses that had a smooth and black surface,with each of them having a length and diameter of approximately 1 cm.Melanosis of the mucosa around the lumen was observed at 40 cm from the incisors to the cardia;the dentate margin was clear;and the cardia had no stenosis.The patient then received five courses of combination therapy and became consistently stable after partial remission.No severe adverse events related to the immunotherapy were recorded.Camrelizumab may be a viable treatment option for patients with PMME.Additional evidence from future clinical trials and research is necessary to fully validate our findings.

Cell transplantation therapy using pluripotent stem cells

The 2012 Nobel Prize in Physiology or Medicine was awarded jointly to Sir John B Gurdon and Shinya Yamanaka "for the discovery that mature cells can be reprogrammed to become pluripotent". Professor John B Gordon who pioneered the field of somatic cell nuclear transfer was the first to show that a nucleus of a mature cell can be transplanted into an enucleated egg and give rise to a living organism. His pioneering "cloning" technique paved the way for genome reprogramming and has led to subsequent cloning of differentanimal species. Professor Shinya Yamanaka revolutionized the filed of stem cell production by showing that the introduction of four selected genes into cells transform them into induced pluripotent stem cells that resemble embryonic stem cells and serve as promising cells for future regenerative medicine.

First-line atezolizumab plus chemotherapy in treatment of extensive small cell lung cancer:a cost-effectiveness analysis from China

Background:IMpower 133 trial first confirmed the efficacy and safety of adding atezolizumab or placebo to first-line treatment with chemotherapy in patients with extensive-stage small-cell lung cancer(SCLC).While,overprice limited its broad use in clinical.The aim of this study was to evaluate the cost-effectiveness of atezolizumab plus chemotherapy in treatment of extensive SCLC as first line in China.Methods:A Markov model was established by extracting data from the IMpower 133 trial with untreated extensive SCLC patients.Utility values were obtained from published studies,and the costs were acquired from real world and literature.Additionally,sensitivity analyses based on a willingness-to-pay(WTP)threshold were performed to identify the uncertain parameters of Markov model.Results:Total costs of atezolizumab group were$48,129,while cost of chemotherapy alone was just$12,920 in placebo group.The quality-adjusted life-years(QALYs)in atezolizumab group was just 0.072 higher than that in placebo group(0.858 QALYs vs.0.786 QALYs).The cost-effectiveness ratio between atezolizumab combination with chemotherapy and chemotherapy alone was$489,013/QALY in China.The net benefit of placebo group was significantly higher than atezolizumab group.One-way sensitivity analyses highlighted that utilities of the progression-free survival(PFS)and progression disease state in placebo group were the most influential parameter.Conclusions:Atezolizumab combination therapy was not more cost-effective than chemotherapy alone at a WTP threshold of$25,929/QALY in China.

夏枯草提取物对人T淋巴瘤Jurkat细胞增殖的影响及机制探讨(英文)

Objective:The aim of this study was to observe the effect of the Prunella vulgaris L extract on the Jurkat human T lymphoma cell line.Methods:Jurkat cells were cultivated with different concentrations of the extract from Prunella vulgaris L.The MTT assay and flow cytometry were employed to determine the cells' proliferation inhibition ratio and the apoptosis rates,respectively.Agarose gel electrophoresis was used to observe cellular DNA fragmentation,and western blotting was used to observe changes in Bcl-2 and Bax protein expression.Results:The Prunella vulgaris L extract remarkably inhibited the proliferation of Jurkat cells.This inhibition exhibited dose dependence,with an IC50 of 20.23 ± 0.31 μg/mL.Agarose gel electrophoresis showed that the apoptosis strap became wider and brighter,and flow cytometry showed that the apoptosis rate increased in a concentration-dependent manner.Western blotting showed that Bcl-2 protein was down-regulated and Bax protein was up-regulated during apoptosis.Conclusion:The extract from Prunella vulgaris L induced apoptosis of Jurkat cells by down-regulating Bcl-2 protein and up-regulating Bax protein.These actions inhibited the growth of Jurkat cells.

卡孕栓、双氯芬酸钠栓在宫颈癌后装放疗术中镇痛效果的临床分析(英文)

Objective:To observe the effects of Methyl Carboprost and Diclofenac Sodium on opening orifice of uterus and pain controlling in patients with uterine cervix cancer (UCC) when receiving intracavitary brachytherapy. Methods: Sixty patients with UCC of stage IIA-IIIB were divided into three groups randomly before receiving the intracavitary brachytherapy: the patients in group A received Methyl Carboprost in the hind fornix of the vagina, group B received Diclofenac Sodium in the anus, while group C was the control group. Results: The painlessness rates in groups A, B and C were 89.9%, 91.3% and 36.4%, respectively. The incidences of patients with relaxed uterus cervix in groups A, B and C were 91.7%, 85.9% and 48.9%, respectively. Conclusion: Methyl Carboprost and Diclofenac Sodium are useful in relaxing uterus cervix and pain controlling in patients with UCC when receiving intracavitary brachytherapy.

外照射配合肝动脉栓塞治疗不能手术切除的原发性肝癌的临床研究(英文)

Objective: This study evaluated the therapeutic effect of external beam radiotherapy (RT) combined with trans- catheter arterial chemoembolization (TACE) on the patients with unresectable hepatocellular carcinoma (HCC). Methods: From June 1994 to April 2002, 114 patients with unresectable HCC were nonrandomized prospectively stepped into our study. All patients received TACE as initial therapy, except 54 also received combination therapy with external beam therapy. Sur- vival failure patterns were analyzed and compared between the two groups. Results: Overall survival rates in the patients in the radiotherapy group were 65%, 47%, 38% at 1, 2, 3 years, respectively, improved over the non-radiotherapy group rates of 54%, 36.5%, 18% at 1, 2, 3 years, respectively. There was significant difference between two groups (P < 0.05). The survival rates correlated with tumor size, number of tumors, and portal vein embolus. Conclusion: TACE combined with RT is a more effective treatment than TACE alone in patients with unresectable HCC.

ERCC1 Asn118Asn基因多态性在预测晚期大肠癌患者奥沙利铂化疗疗效中的应用(英文)

Objective: To assess whether the polymorphism of ERCC1 Asn118Asn (C → T) had effects on cancer response to chemotherapy and outcome in Chinese patients treated with oxaliplatin as first-line chemotherapy regimen for advanced colorectal cancer. Methods: ERCC1 Asn118Asn polymorphism was analyzed in 99 patients with stages III and IV advanced colorectal cancer treated with oxaliplatin-based chemotherapy. For all of the patients, ERCC1 Asn118Asn genotype was analyzed for associations with treatment response and time to disease progress (TTP). Results: The allele frequencies of the ERCC1 gene codon 118 were C/C 50.51% (50/99), C/T 41.41% (41/99), T/T 8.08% (8/99), respectively. Patients with C/C genotype showed higher response rate than those with C/T + T/T (OR = 3.764, 95% CI: 1.310-10.813). The median TTP of all patients was 7 months (95% CI: 5.569-8.431). Patients with C/C genotype showed a median TTP of 10 months (95% CI: 8.924-11.076), which was longer than 5 months (95% CI: 4.424-5.576) in patients with C/T + T/T genotypes. Conclusion: Our results showed a link between ERCC1 Asn118Asn genetic polymorphism and cancer response to oxaliplatin-based che- motherapy and time to disease progress in Chinese patients with advanced colorectal cancer. ERCC1 Asn118Asn genotyping may be of predictive benefit in selecting treatment regimen for advanced colorectal cancer.

Potential for a pluripotent adult stem cell treatment for acute radiation sickness

Accidental radiation exposure and the threat of deliberate radiation exposure have been in the news and are a public health concern. Experience with acute radiation sickness has been gathered from atomic blast survivors of Hiroshima and Nagasaki and from civilian nuclear accidents as well as experience gained during the development of radiation therapy for cancer. This paper reviews the medical treatment reports relevant to acute radiation sickness among the survivors of atomic weapons at Hiroshima and Nagasaki, among the victims of Chernobyl, and the two cases described so far from the Fukushima Dai-Ichi disaster. The data supporting the use of hematopoietic stem cell transplantation and the new efforts to expand stem cell populations ex vivo for infusion to treat bone marrow failure are reviewed. Hematopoietic stem cells derived from bone marrow or blood have a broad ability to repair and replace radiation induced damaged blood and immune cell production and may promote blood vessel formation and tissue repair. Additionally, a constituent of bone marrow-derived, adult pluripotent stem cells, very small embryonic like stem cells, are highly resistant to ioniz-ing radiation and appear capable of regenerating radiation damaged tissue including skin, gut and lung.

PICOT promotes T lymphocyte proliferation by down-regulating cyclin D2 expression

The mammalian protein kinase C-interacting cousin of thioredoxin(PICOT;also termed glutaredoxin 3)is a multi-domain monothiol glutaredoxin that is involved in a wide variety of signaling pathways and biological processes.PICOT is required for normal and transformed cell growth and is critical for embryonic development.Recent studies in T lymphocytes demonstrated that PICOT can translocate to the nucleus and interact with embryonic ectoderm development,a polycomb group protein and a core component of the polycomb repressive complex 2,which contributes to the maintenance of transcriptional repression and chromatin remodeling.Furthermore,PICOT was found to interact with chromatin-bound embryonic ectoderm development and alter the extent of histone 3 lysine 27 trimethylation at the promoter region of selected polycomb repressive complex 2 target genes.PICOT knockdown in Jurkat T cells led to increased histone 3 lysine 27 trimethylation at the promoter region of CCND2,a cell cycle-regulating gene which encodes the cyclin D2 protein.As a result,the expression levels of CCND2 mRNA and protein levels were reduced,concomitantly with inhibition of the cell growth rate.Analysis of multiple data sets from the Cancer Genome Atlas revealed that a high expression of PICOT correlated with a low expression of CCND2 in a large number of human cancers.In addition,this parameter correlated with poor patient survival,suggesting that the ratio between PICOT/CCND2 mRNA levels might serve as a predictor of patient survival in selected types of human cancer.