Use of Initial Modified RECIST Tumor Response Evaluation Criteria for Predicting Survival in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization with Drug-Eluting Beads

Introduction: Transarterial chemoembolization (TACE) reduces tumor growth and increases survival in patients with hepatocellular carcinoma (HCC). Drug-eluting beads (DEB) deliver slow-release chemotherapy and reduce systemic toxicity during TACE. This study correlated initial tumor response according to modified RECIST (mRECIST) criteria and 1-year survival in patients with HCC treated with TACE-DEB, and identified predictors of tumor response. Methods: Fifty-two patients with HCC received TACE-DEB loaded with doxorubicin 75 mg during a 6-month period. Tumor response was evaluated 1 month after the procedure according to mRECIST criteria. Results: Most patients were cirrhotic and etiology of liver disease was hepatitis C in 26/52 (50%). Similar numbers of patients had Barcelona Clinic Liver Cancer (BCLC) A and BCLC B disease. Most patients had one nodule (66%). Complete response (CR) was achieved in 12/52 (23%), partial response in 19/52 (37%), stable disease in 4/52 (8%) and progressive disease in 17/52 (32%). Largest HCC ≤58 mm and BCLC stage A were associated with CR. The 1-year survival was 74%, with survival rates of 95% and 56% in the BCLC A and B groups, respectively. Variables reflecting tumor extension were associated with better survival. CR according to mRECIST criteria was a predictor of better 1-year survival (100% vs. 64%, P < 0.05). Conclusion: BCLC A and CR according to mRECIST criteria predict improved 1-year survival in patients with HCC treated with TACE-DEB. Further studies are needed to evaluate other predictors of survival and to determine if tumor response predicts long-term survival.

Prognostic Significance of Neuroendocrine Differentiation in Non-small Cell Lung Cancer Patients' Survival

Objective： To observe the relationship between non-small cell lung cancer with neuroendrocrine differentiation （NSCLC-NE） and patients＇ postoperative survival. Methods： During April 1997 to April 1999, 98 cases of hlng cancer were surgically treated. The tumor specimens of the patients were stained by NE markers, i.e. neuron specific enolase （NSE） and synaptophysin （SY）. The intensity of NE markers reaction was divided as ＂＋＂. ＂＋＋＂. ＂＋＋＋＂ scale groups. The same specimens were also examined under an electron microscope for the specific neuroendocrine granules. All enrolled patients were followed up for 36 months, and the longest follow-up time was 60 months. The COX proportional hazard model multivariate analysis was applied to observe the relationship between the NSCLE-NE and the patients＇ postoperative survival. Results： In 91 cases of NSCLC, 63.7% （58/91） were positive for NE stain reaction. Among them, 59.3% （54/91） were positive for NSE and 24.1% （22/91） for SY. 48.4% （44/91） were considered as NSCLC-NE by the combination of NE inarker stain reaction and electron microscopic examination. COX proportional hazard model lnnltivariate analysis showed that the NSCLC-NE patients＇ survival was significantly shortened （P=0.048）. The following factors were related to NSCLC-NE patients＇ survival： lung cancer cell differentiation （P=0.006）, clinical lung cancer stage （P=0.001）, the NE markers reaction （P=0.054）. Conclusion： NSCLE-NE is significantly related to the cancer cell differentiation and the patients＇ postoperative survival. The NE markers should be applied clinically as one of prognostic factors to evaluate the postoperative survival of NSCLC patients.

Micronuclei and cell survival in human liver cancer cells irradiated by 25MeV/u^(40)Ar^(14+)

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Cumulative scores based on plasma D-dimer and serum albumin levels predict survival in esophageal squamous cell carcinoma patients treated with transthoracic esophagectomy

Background:Recently,studies have shown that plasma D-dimer and serum albumin are prognostic markers for esophageal cancer.The purpose of this study was to evaluate a novel prognostic scoring system—DA score(combination of preoperative plasma D-dimer and serum albumin levels)—and analyze the association between survival of patients with esophageal squamous cell carcinoma(ESCC) and their Glasgow prognostic score.Methods:In this retrospective study,preoperative biochemical markers and clinicopathologic factors in 260 ESCC patients treated with transthoracic esophagectomy were reviewed.According to receiver operating characteristic analysis,the cutoff values of D-dimer and albumin were defined as 0.5 μg/mL and 43.8 g/L,respectively.Patients with high D-dimer levels(>0.5 μg/mL) and low albumin levels(<43.8 g/L) were assigned a score of 2,those with only one of the two abnormalities were assigned a score of 1,and those with neither of the two abnormalities were assigned a score of 0.Results:ESCC patients with a DA score of 0,l,and 2 numbered 55,116,and 89,respectively.Survival analysis showed that patients with a DA score of 2 had lower overall survival(OS) rates than those with DA scores of 1 and 0(37.1%vs.52.6%and 76.4%,P < 0.001);similar findings were observed for disease-free survival(DFS) rates(32.6%vs.44.8%and67.3%,P < 0.001).In addition,the predictive value of the DA score was also significant in patients with stages l-IIA and stages IIB-IV ESCC.Multivariate Cox regression analyses indicated that hazard ratios(HRs) for predicting OS of patients with DA scores 1 and 2 were 2.25 {P — 0.010) and 3.14(P< 0.001),respectively,compared with those with a DA score of 0,and HRs for predicting DFS of patients with DA scores of 1 and 2 were 1.86(P = 0.023) and 2.68(P < 0.001),respectively,compared with those with a DA scores of 0.Conclusions:Our study suggests that preoperative DA scores are notably associated with postoperative survival of ESCC patients.

Nomograms based on HPV load for predicting survival in cervical squamous cell carcinoma: An observational study with a longterm follow-up

Objective: To investigate the prognostic value of pretreatment human papillomavirus(HPV) viral load for cervical cancer, and to develop nomograms based on HPV load and other clinicopathological factors for long-term survival.Methods: We conducted a prospective study on cervical squamous cell carcinoma(SCC) patients diagnosed between January 2003 and December 2008. Cervical samples were tested for HPV viral load by the Hybrid Capture II(HCII) assay before treatment and 6 months after treatment. Clinical characteristics and follow-up information were also collected. A multivariable Cox proportional hazards model was used to adjust covariates in both the radical hysterectomy(RH) treatment group and concurrent chemoradiotherapy(CCRT) treatment group to identify relevant covariates, and then nomograms were constructed and used for internal validation.Results: A total of 520 SCC patients enrolled in this study with a median follow-up of 127 months, 360 patients received RH, whereas 160 patients received CCRT. The median HPV viral load in RH and CCRT groups was356.10 and 294.29, respectively. Tumor size was positively correlated with high pretreatment HPV load in both groups. In CCRT group, the advanced International Federation of Gynecology and Obstetrics(FIGO) stage and enlarged retroperitoneal lymph node status determined by computed tomography(LNSCT) were correlated with low HPV load group. Initial HPV viral load, FIGO stage and lymph node metastasis were prognostic factors for RH group, whereas HPV viral load, squamous cell carcinoma antigen(SCC-Ag) level and LNSCT were identified as prognostic factors for CCRT group. Nomograms incorporating these predictors for 10-year progression-free survival(PFS) were constructed [concordance index(C-index): 0.756, 0.749].Conclusions: A low pretreatment HPV viral load is an independent prognostic factor for poor prognosis of cervical SCC and is related to other clinicopathological factors. The survival nomogram based on HPV viral load could predict the long-term prognosis.

Role of adipose-derived stromal cells in pedicle skin flap survival in experimental animal models

The use of skin flaps in reconstructive surgery is the first-line surgical treatment for the reconstruction of skin defects and is essentially considered the starting point of plastic surgery. Despite their excellent usability, their application includes general surgical risks or possible complications, the primary and most common is necrosis of the flap. To improve flap survival, researchers have used different methods, including the use of adiposederived stem cells, with significant positive results. In our research we will report the use of adipose-derived stem cells in pedicle skin flap survival based on current literature on various experimental models in animals.

Long-term survival outcomes of video-assisted thoracic surgery for patients with non-small cell lung cancer

Background： Video-assisted thoracic surgery （VATS） has been shown to be a safe alternative to conventional thoracotomy for patients with non-small cell lung cancer （NSCLC）. However, popularization of this relatively novel technique has been slow, partly due to concerns about its long-term outcomes. The present study aimed to evaluate the long-term survival outcomes of patients with NSCLC after VATS, and to determine the significant prognostic factors on overall survival. Methods： Consecutive patients diagnosed with NSCLC referred to one institution for VATS were identified from a central database. Patients were treated by either complete-VATS or assisted-VATS, as described in previous studies. A number of baseline patient characteristics, clinicopathologic data and treatment-related factors were analyzed as potential prognostic factors on overall survival. Results： Between January 2000 and December 2007, 1,139 patients with NSCLC who underwent VATS and fulfilled a set of predetermined inclusion criteria were included for analysis. The median age of the entire group was 60 years, with 791 male patients （69%）. The median 5-year overall survival for Stage Ⅰ, Ⅱ, Ⅲ and Ⅳ disease according to the recently updated TNM classification system were 72.2%, 47.5%, 29.8% and 28.6%, respectively. Female gender, TNM stage, pT status, and type of resection were found to be significant prognostic factors on multivariate analysis. Conclusions： VATS offers a viable alternative to conventional open thoracotomy for selected patients with clinically resectableNSCLC

Survival and death of endoplasmic-reticulum-stressed cells:Role of autophagy

Accumulation of unfolded proteins in the endoplasmic reticulum (ER) results in ER stress, which subsequently activates the unfolded protein response that induces a transcriptional program to alleviate the stress. Another cellular process that is activated during ER stress is autophagy, a mechanism of enclosing intracellular compo- nents in a double-membrane autophagosome, and then delivering it to the lysosome for degradation. Here, we discuss the role of autophagy in cellular response to ER stress, the signaling pathways linking ER stress to autophagy, and the possible implication of modulating autophagy in treatment of diseases such as cancer.

A radiomics prognostic scoring system for predicting progression-free survival in patients with stageⅣnon-small cell lung cancer treated with platinum-based chemotherapy

Objective:To develop and validate a radiomics prognostic scoring system(RPSS)for prediction of progressionfree survival(PFS)in patients with stageⅣnon-small cell lung cancer(NSCLC)treated with platinum-based chemotherapy.Methods:In this retrospective study,four independent cohorts of stageⅣNSCLC patients treated with platinum-based chemotherapy were included for model construction and validation(Discovery:n=159;Internal validation:n=156;External validation:n=81,Mutation validation:n=64).First,a total of 1,182 three-dimensional radiomics features were extracted from pre-treatment computed tomography(CT)images of each patient.Then,a radiomics signature was constructed using the least absolute shrinkage and selection operator method(LASSO)penalized Cox regression analysis.Finally,an individualized prognostic scoring system incorporating radiomics signature and clinicopathologic risk factors was proposed for PFS prediction.Results:The established radiomics signature consisting of 16 features showed good discrimination for classifying patients with high-risk and low-risk progression to chemotherapy in all cohorts(All P<0.05).On the multivariable analysis,independent factors for PFS were radiomics signature,performance status(PS),and N stage,which were all selected into construction of RPSS.The RPSS showed significant prognostic performance for predicting PFS in discovery[C-index:0.772,95%confidence interval(95%CI):0.765-0.779],internal validation(C-index:0.738,95%CI:0.730-0.746),external validation(C-index:0.750,95%CI:0.734-0.765),and mutation validation(Cindex:0.739,95%CI:0.720-0.758).Decision curve analysis revealed that RPSS significantly outperformed the clinicopathologic-based model in terms of clinical usefulness(All P<0.05).Conclusions:This study established a radiomics prognostic scoring system as RPSS that can be conveniently used to achieve individualized prediction of PFS probability for stageⅣNSCLC patients treated with platinumbased chemotherapy,which holds promise for guiding personalized pre-therapy of stageⅣNSCLC.

Antibody-platinum(IV)prodrugs conjugates for targeted treatment of cutaneous squamous cell carcinoma

Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.

Is there an optimal time to initiate adjuvant chemotherapy to predict benefit of survival in non-small cell lung cancer?

Objective: Adjuvant chemotherapy (AC) after curative resection is known to improve the survival of patients with non-small cell lung cancer (NSCLC); however, few studies have reported the correlation between the time to initiation of AC (TTAC) and survival in NSCLC patients. Methods: The clinical data of 925 NSCLC patients who received curative resection and post-operative AC at the Cancer Hospital of Chinese Academy of Medical Sciences between 2003 and 2013 were retrospectively analyzed. TTAC was measured from the date of surgery to the initiation of AC. Disease-free survival (DFS) was defined as the duration from surgery to the time of tumor recurrence or last follow-up evaluation. The optimal cut-off value of TTAC was determined by maximally selected log-rank statistics. The DFS curve was estimated using the Kaplan-Meier method, and the Cox proportional hazards regression model was used to identify risk factors independently associated with DFS. Propensity score matching (PSM) was performed for survival analysis using the match data. Results: The optimal discriminating cut-off value of TTAC was set at d 35 after curative resection based on which the patients were assigned into two groups: group A (<= 35 d) and group B (> 35 d). There was no significant difference in the DFS between the two groups (P=0.246), indicating that the TTAC is not an independent prognostic factor for DFS. A further comparison continued to show no significant difference in the DFS among 258 PSM pairs (P=0.283). Conclusions: There was no significant correlation between the TTAC and DFS in NSCLC patients. Studies with larger samples are needed to further verify this conclusion.

Efect of body mass index on survival of patients with stage I non-small cell lung cancer

Background:Body mass index(BMI)has a U?shaped association with lung cancer risk.However,the effect of BMI on prognosis is controversial.This retrospective study aimed to investigate the effect of BMI on the survival of patients with stage I non?small cell lung cancer(NSCLC)after surgical resection.Methods:In total,624 consecutive stage I NSCLC patients who underwent radical resection were classified into four groups according to their BMI:underweight(BMI<18.5 kg/m^2),normal weight(BMI obese(BMI>28.0 kg/m^2).The effect of BMI on progress=18.5–22.4 kg/m2),overweight(BMI=22.5–28.0 kg/m^2),andion?free survival(PFS)and over?all survival(OS)was estimated using the Kaplan–Meier method and Cox proportional hazards model.Postoperative complications in each group were analyzed using the Chi square test or Fisher’s exact test.Results:A univariate analysis showed that PFS and OS were longer in the overweight group than in other groups(both P<0.05).A multivariate analysis showed that OS was longer in the overweight group than in other groups(compared with the other three groups in combination:hazard ratio[HR]e underweight group:HR=1.87,95%confidence interval[CI]1.30–2.68,P=0.003;compared with th3,P=2.24,95%CI 1.18–4.25,P=0.013;compared with the normal weight group:HR 1.48–5.59,P=1.58,95%CI 1.07–2.3=0.022;compared with the obese group:HR=2.87,95%CIwe=0.002),but PFS was similar among the groups(HRd an association between being overweight and pro=1.28,95%CI 0.97–1.68,P longed OS in patients at sta=0.080).A subgroup analysis shoge T1a(P 0.001).Overweight=0.024),T1b(P=0.051),and T2a(P=0.02),as well as in patients with a non?smoking history(P=patients had lower rates of postoperative complications,such as respiratory failure(compared with the underweight and obese groups:P=0.014),myocardial infarction(compared with the obese group:P=0.033),and perioperative death(com?pared with the other three groups:P=0.016).Conclusions:Preoperative BMI is an independent prognostic factor for stage I NSCLC patients after resection,with overweight patients having a favorable prognosis.

Stem cell technology for antitumor drug loading and delivery in oncology

The main aim of antineoplastic treatment is to maximize patient benefit by augmenting the drug accumulation within affected organs and tissues,thus incrementing drug effects and,at the same time,reducing the damage of non-involved tissues to cytotoxic agents.Mesenchymal stromal cells(MSC)represent a group of undifferentiated multipotent cells presenting wide self-renewal features and the capacity to differentiate into an assortment of mesenchymal family cells.During the last year,they have been proposed as natural carriers for the selective release of antitumor drugs to malignant cll,s thus optimizing cytotoxic action on cancer cll,while significantly reducing adverse side efect on healthy cells.MSC chemotherapeutic drug loading and delivery is an encouraging new area of cell therapy for several tumors,especially for those with unsatisfactory prognosis and limited treatment options available.Although some experim ental models have been sucesfuly developed,phase I dinical studies are needed to confirm this potential application of cell therapy,in particular in the case of primary and secondary lung cancers.

Prox1 Suppresses Proliferation and Drug Resistance of Retinoblastoma Cells via Targeting Notch1

Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,hepatocyte,pancreatic,heart,lens,retinal,and cancer cells.The goal of this study was to investigate the role of Prox1 in RB cell proliferation and drug resistance,as well as to explore the underlying Notch1 mechanism.Methods Human RB cell lines(SO-RB50 and Y79)and a primary human retinal microvascular endothelial cell line(ACBRI-181)were used in this study.The expression of Prox1 and Notch1 mRNA and protein in RB cells was detected using quantitative real time-polymerase chain reaction(RT-qPCR)and Western blotting.Cell proliferation was assessed after Prox1 overexpression using the Cell Counting Kit-8 and the MTS assay.Drug-resistant cell lines(SO-RB50/vincristine)were generated and treated with Prox1 to investigate the role of Prox1 in drug resistance.We employed pcDNA-Notch1 to overexpress Notch1 to confirm the role of Notch1 in the protective function of Prox1.Finally,a xenograft model was constructed to assess the effect of Prox1 on RB in vivo.Results Prox1 was significantly downregulated in RB cells.Overexpression of Prox1 effectively decreased RB cell growth while increasing the sensitivity of drug-resistant cells to vincristine.Notch1 was involved in Prox1’s regulatory effects.Notch1 was identified as a target gene of Prox1,which was found to be upregulated in RB cells and repressed by increased Prox1 expression.When pcDNA-Notch1 was transfected,the effect of Prox1 overexpression on RB was removed.Furthermore,by downregulating Notch1,Prox1 overexpression slowed tumor development and increased vincristine sensitivity in vivo.Conclusion These data show that Prox1 decreased RB cell proliferation and drug resistance by targeting Notch1,implying that Prox1 could be a potential therapeutic target for RB.

Effects of insurance status on long-term survival among non-small cell lung cancer(NSCLC) patients in Beijing,China: A population-based study

Objective: To evaluate the effects of health insurance status on long-term cancer-specific survival of non-small cell lung cancer(NSCLC) in Beijing, China, using a population-based cancer registry data.Methods: Information on NSCLC patients diagnosed in 2008 was derived from the Beijing Cancer Registry.The medical records of 1,134 cases were sampled and re-surveyed to obtain information on potential risk factors.Poorly-insured status was defined as Uninsured and New Rural Cooperative Medical Insurance Scheme(NRCMS),while well-insured included Urban Employees Basic Medical Insurance(UEBMI) and Free Medical Care(FMC).To estimate survival outcomes, individuals were followed-up until December 31, 2018. Cancer-specific survival probabilities at 5 and 10 years after diagnosis were estimated using the Kaplan-Meier method. Log-rank test was used to compare long-term survival with different characteristics. Multivariable Cox proportional hazard regression model was used to examine the relative effect of insurance status on cancer-specific mortality.Results: Well-insured NSCLC patients have longer cancer-specific survival than poorly-insured individuals[hazard ratio(HR)=0.81;95% confidence interval(95% CI): 0.67-0.97), even after adjusting for age, gender, cancer stage, smoking status, family history and residential area. Older age and rural residence were associated with a higher risk of cancer-specific mortality(HR=1.03;95% CI: 1.02-1.03 and HR=1.25;95% CI: 1.07-1.46,respectively). Smoking individuals had a 41% higher long-term cancer-specific mortality risk than non-smoking ones(HR=1.41;95% CI: 1.20-1.66).Conclusions: NSCLC patients with good insurance status had better survival rates than those with poor insurance. An association was significant even after 10 years. Large population-based studies are needed to validate that high reimbursement insurance status can lead to the improvement of long-term cancer prognosis in China.

Activation of the ERK 1/2 and STAT3 signaling pathways is required for 661W cell survival following oxidant injury

AIM: To evaluate the influence of hydrogen peroxide (H2O2) on mouse photoreceptor-derived 661W cell survival and to determine the effect of PD98059, an inhibitor for MEK1 (the direct upstream activator of ERK1/2), and S3I201, a STAT3-specific inhibitor on 661W cell survival after H2O2 exposure. METHODS: The mouse photoreceptor-derived 661W cells were cultured. 661W cells were treated for 12 hours with different concentrations (0, 0.25, 0.50, 0.75, 1mmol/L) of H2O2 and cell viability was determined by 3- (4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) (MTT) assay. 661W cells were treated with different concentrations H2O2 (0, 5, 10, 50, 500, 1000 mu mol/L) for 15 minutes or 1mmol/L H2O2 for different time points (0,5,10,15,30 minutes), and p-Tyr705-STAT3, STAT3, Phospho-p44/42 MAPK (Thr202/Tyr204), ERK1/2 were surveyed by immunoblot analysis. After treatment with 50 mu mol/L PD98059, or S3I201 for 1 hour, the inhibition efficiency of cell signal pathways was analyzed by immunoblot analysis and the effects of inhibitors on cell viability were determined by MTT. RESULTS: After treating with different concentrations of H2O2 for 12 hours, the cell viability of 661W cells decreased in concentration-dependent manner (P<0.05). Moreover, H2O2 induced phosphorylation of ERK1/2 and STAT3 in 661W cells (P <0.05). After pretreatment with 50 mu mol/L PD98059 or S3I201 for 1 hour, H2O2-induced phosphorylation of ERK1/2 or STAT3 was suppressed separately (P<0.05). Using PD98059 or S3I201 to inhibit ERK1/2 or STAT3 signal pathway, the cell viability of 661W cells decreased significantly (P<0.05). CONCLUSION: We demonstrated that the exposure of 661W cells to H2O2 increased the activation of ERK1/2 and STAT3 signal pathways. Activation of these pathways is required for 661W cell survival following oxidant injury.

The recurrence and survival of oral squamous cell carcinoma: a report of 275 cases

Oral squamous cell carcinoma(OSCC) is a common malignant tumor of the head and neck, and recurrence is an important prognostic factor in patients with OSCC. We explored the factors associated with recurrence of OSCC and analyzed the survival of patients after recurrence. Clinicopathologic and follow-up data of 275 patients with OSCC treated by surgery in the Cancer Institute and Hospital of Tianjin Medical University between 2002 and 2006 were analyzed. Recurrence factors were analyzed with Chisquare or Fisher′s exact test and multivariate analysis. The prognosis of patients after recurrence was analyzed with the Kaplan-Meier method and log-rank test. The recurrence rate was 32.7%. The recurrence time ranged from 2 to 96 months, with a median of 14 months. Univariate analysis showed that T stage, degree of differentiation, pN stage, flap application, resection margin, and lymphovascular invasion were factors of recurrence (P<0.05). Multivariate analysis showed that T stage, degree of differentiation, and pN stage were independent factors of recurrence (P<0.001). The differences in gender, age, tumor site, region of lymph node metastasis, and perineural invasion between the recurrence and non-recurrence groups were not significant (P>0.05). Kaplan-Meier and log-rank tests showed that the 2- and 5-year survival rates were significantly lower in the recurrence group than in non-recurrence group(67.6% vs. 88.0%, 31.8% vs. 79.9%, P<0.001). Therefore, to improve prognosis, we recommend extended local excision, flap, radical neck dissection, and adjuvant chemoradiotherapy for patients more likely to undergo recurrence.

Day 100 Absolute Monocyte/Lymphocyte Prognostic Score and Survival Post Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation in Diffuse Large B-Cell Lymphoma

Day 100 prognostic factors post-autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT) to predict clinical outcomes in diffuse large B-cell lymphoma (DLBCL) patients have not been studied. Thus, we retrospectively examined if day 100 absolute monocyte/lymphocyte prognostic score (AMLPS-100) affects clinical outcomes by landmark analysis from day 100 post-APBHSCT in DLBCL. Only DLBCL patients in complete remission at day 100 post-APBHSCT were evaluated. From 2000 to 2007, 134 consecutive DLBCL patients are qualified for the study. Patients with a day 100 absolute monocyte count (AMC-100) ≥ 630 cells/μL and day 100 absolute lymphocyte count (ALC-100) ≤ 1000 cells/μL experienced inferior overall survival (OS) and progression free survival (PFS). On multivariate analysis, the AMC-100 and ALC-100 remained independent predictors of OS and PFS. Combining both values into the AMLPS-100, the 5-year OS rates for low, intermediate, and high AMLPS-100 risk groups were 94% (95% CI, 83.0% - 98.1%), 70% (95% CI, 58.6% - 80.1%), and 13% (95% CI, 3.4% - 40.5%), respectively;and the 5-year PFS rates were 87% (95% CI, 74.0% - 94.1%), 68% (95% CI, 56.0% - 77.8%), and 13% (95% CI, 3.4% - 40.5%), respectively. The AMLPS-100 is a simple biomarker score that can stratify clinical outcomes from day 100 post-APBHSCT in DLBCL patients.

Fortuitous benefits of activity-based rehabilitation in stem cell-based therapy for spinal cord repair: enhancing graft survival

Traumatic injuries to spinal cord elicit diverse signaling pathways leading to unselective and complex pathological outcomes：death of multiple classes of neural cells,formation of cystic cavities and glial scars,disruption of axonal connections,and demyelination of spared axons,all of which can contribute more or less to debilitating functional impairments found in patients with spinal cord injury.

Human mesenchymal stem cells exhibit altered mitochondrial dynamics and poor survival in high glucose microenvironment

BACKGROUND Mesenchymal stem cells(MSCs)are a type of stem cells that possess relevant regenerative abilities and can be used to treat many chronic diseases.Diabetes mellitus(DM)is a frequently diagnosed chronic disease characterized by hyperglycemia which initiates many multisystem complications in the long-run.DM patients can benefit from MSCs transplantation to curb down the pathological consequences associated with hyperglycemia persistence and restore the function of damaged tissues.MSCs therapeutic outcomes are found to last for short period of time and ultimately these regenerative cells are eradicated and died in DM disease model.AIM To investigate the impact of high glucose or hyperglycemia on the cellular and molecular characteristics of MSCs.METHODS Human adipose tissue-derived MSCs(hAD-MSCs)were seeded in low(5.6 mmol/L of glucose)and high glucose(25 mmol/L of glucose)for 7 d.Cytotoxicity,viability,mitochondrial dynamics,and apoptosis were deplored using specific kits.Western blotting was performed to measure the protein expression of phosphatidylinositol 3-kinase(PI3K),TSC1,and mammalian target of rapamycin(mTOR)in these cells.RESULTS hAD-MSCs cultured in high glucose for 7 d demonstrated marked decrease in their viability,as shown by a significant increase in lactate dehydrogenase(P<0.01)and a significant decrease in Trypan blue(P<0.05)in these cells compared to low glucose control.Mitochondrial membrane potential,indicated by tetramethylrhodamine ethyl ester(TMRE)fluorescence intensity,and nicotinamide adenine dinucleotide(NAD+)/NADH ratio were significantly dropped(P<0.05 for TMRE and P<0.01 for NAD+/NADH)in high glucose exposed hAD-MSCs,indicating disturbed mitochondrial function.PI3K protein expression significantly decreased in high glucose culture MSCs(P<0.05 compared to low glucose)and it was coupled with significant upregulation in TSC1(P<0.05)and downregulation in mTOR protein expression(P<0.05).Mitochondrial complexes I,IV,and V were downregulated profoundly in high glucose(P<0.05 compared to low glucose).Apoptosis was induced as a result of mitochondrial impairment and explained the poor survival of MSCs in high glucose.CONCLUSION High glucose impaired the mitochondrial dynamics and regulatory proteins in hAD-MSCs ensuing their poor survival and high apoptosis rate in hyperglycemic microenvironment.