Chemotherapy-Induced Cognitive Decline: Moving from the Mechanistic Debate towards Prevention and Treatment—A Clinical Review

Patients receiving chemotherapy have reported cognitive challenges including short-term memory loss and reduced executive functioning. While cognitive decline can be multifactorial and related to aging, depression, surgery, and other medications, there has been a steadily increasing body of knowledge showing a significant association between cognitive decline and chemotherapy administration. This clinical review summarizes patient-reported cognitive changes, support from neuroimaging and neuropsychological testing. The mechanism of action of and patient susceptibilities to cognitive decline are reviewed. Current behavioral and pharmacologic interventions are discussed. There is a need to identify patients at risk for developing chemotherapy induced cognitive decline and?to?screen for early signs of cognitive deterioration. The risk of cognitive dysfunction and possible interventions should be included in the informed consent discussion with patients who are undergoing cytotoxic treatments.

Micro RNA-145 exerts tumor-suppressive and chemoresistance lowering effects by targeting CD44 in gastric cancer

AIM To determine the potential roles of CD4 and micro RNA(mi R)-145 in gastric cancer.METHODS The levels of CD44 and mi R-145 were determined in gastric cancer cells. Quantitative real-time polymerase chain reaction was used to measure to the level of CD44 m RNA. A luciferase reporter assay and western blotting were performed to examine the effect of mi R-145 on CD44 expression. Tumor sphere and MTT assays were carried out to evaluate the self-renewal and chemo-resistance properties of gastric cancer cells.RESULTS The expression of CD44 was greatly increased and mi R-145 was decreased in gastric cancer cells that were highly enriched in cancer stem cells(CSCs). The results demonstrated that mi R-145 regulated CD44 by targeting directly the CD44 3'-untranslated region(3'-UTR). In gastric cancer cells, overexpression of mi R-145 repressed the activity of the CD44 3'-UTR, and disruption of mi R-145/CD44 3'-UTR interactions abrogated the silencing effects. In addition, mi R-145 inhibition stimulated CD44 3'-UTR activity and disruption of mi R-145/CD44 3'-UTR interactions abrogated this stimulatory effect. Enforced CD44 expression greatly increased tumor sphere formation and chemoresistance in gastric cancer cells. Furthermore, the inhibition of CSCs and the chemo-sensitivity of gastric cancer cells treated with mi R-145 were significantly abrogated by overexpression of CD44. CONCLUSION mi R-145 targeting of CD44 plays critical roles in the regulation of tumor growth and chemo-resistance in gastric cancer.

A general solution for one dimensional chemo-mechanical coupled hydrogel rod

Smart hydrogels are environmentally sensitive hydrogels, which can produce a sensitive response to external stimuli, and often exhibit the characteristics of multi filed coupling. In this paper, a hydrogel rod under chemomechanical coupling was analytically studied based on a poroelastical model. The already known constitutive and governing equations were simplified into the one dimensional case, then two different boundary conditions were considered. The expressions of concentration, displacement,chemical potential and stress related to time were obtained in a series form. Examples illustrate the interaction mechanism of chemical and mechanical effect. It was found that there was a balance state in the diffusion of concentration and the diffusion process could lead to the expansion or the stress change of the hydrogel rod.

Down-staging depth score to predict outcomes in locally advanced rectal cancer achieving ypl stage after neoadjuvant chemo-radiotherapy versus de novo stage pl cohort:A propensity score-matched analysis

Objective：Prognosis of patients with locally advanced rectal cancer（LARC）but achieving yp T1–2N0 stage after neoadjuvant concurrent chemo-radiotherapy（CRT）has been shown to be favorable.This study aims to determine whether the long-term outcome of yp T1–2N0 cases can be comparable to that of p T1–2N0 cohort that received definitive surgery for early disease.Method：From January 2008 to December 2013,449 consecutive patients with rectal cancer were treated and their outcome maintained in a database.Patients with LARC underwent total mesorectal excision（TME）surgery at4–8 weeks after completion of CRT,and those achieving stage yp I were identified as a group.As a comparison,stage p I group pertains to patients whose initially limited disease was not upstaged after TME surgery alone.After propensity score matching（PSM）,comparisons of local regional control（LC）,distant metastasis-free survival（DMFS）,disease-free survival（DFS）and overall survival（OS）were performed using Kaplan-Meier analysis and log-rank test between yp I and p I groups.Down-staging depth score（DDS）,a novel method of evaluating CRT response,was used for subset analysis.Results：Of the 449 patients,168 matched cases were generated for analysis.Five-year LC,DMFS,DFS and OS for stage p I vs.yp I groups were 96.7%vs.96.4%（P=0.796）,92.7%vs.73.6%（P=0.025）,91.2%vs.73.6%（P=0.080）and 93.1%vs.72.3%（P=0.040）,respectively.In the DDS-favorable subset of the yp I group,LC,DMFS,DFS and OS resulted in no significant differences in comparison with the p I group（P=0.384,0.368,0.277 and0.458,respectively）.Conclusions：LC was comparable in both groups;however,distant metastasis developed more frequently in down-staged LARC than de novo early stage cases,reflecting the need to improve the efficacy of systemic treatment despite excellent pathologic response.DDS can be an indicator to identify a subset of the yp I group whose longterm oncologic outcomes are as good as those of stage p I cohort.

Current issues in locally advanced colorectal cancer treated by preoperative chemoradiotherapy

In patients with locally advanced rectal cancer,preoperative chemoradiotherapy has proven to significantly improve local control and cause lower treatmentrelated toxicity compared with postoperative adjuvant treatment.Preoperative chemoradiotherapy followed by total mesorectal excision or tumor specific mesorectal excision has evolved as the standard treatment for locally advanced rectal cancer.The paradigm shift from postoperative to preoperative therapy has raised a series of concerns however that have practical clinical implications.These include the method used to predict patients who will show good response,sphincter preservation,the application of conservative management such as local excision or"wait-and-watch"in patients obtaining a good response following preoperative chemoradiotherapy,and the role of adjuvant chemotherapy.This review addresses these current issues in patients with locally advanced rectal cancer treated by preoperative chemoradiotherapy.

Recent applications of chemosensitivity tests for colorectal cancer treatment

The evaluation of therapeutic efficacy is necessary to predict the outcome of patients with metastatic colorectal cancer(CRC). In these patients, there is a critical need for predictive chemosensitivity assays and biomarkers to optimize efficacy and minimize toxicity. The introduction of targeted agents has improved the progression-free survival and overall survival of patients with metastatic disease. However, approximately 50% of patients do not show a positive response to chemotherapy and the selection of patients likely to respond to a specific regimen remains challenging. Cell culturebased chemosensitivity tests use autologous viable tumor cells to evaluate susceptibility to specific agents in vitro and predict their direct effects. Adenosine triphosphate-based assays and methyl thiazolyl-diphenyltetrazolium bromide-based assays are used widely as sensitivity tests because of their short assay period, technical simplicity, and the requirement of small amount of specimen. Among protein- and gene-based chemosensitivity assays, assessment of KRAS mutation status predicts the response to epidermal growth factor receptor-targeted therapy in CRC patients. The validation of predictive and prognostic markers enables the selection of therapeutic regimens with optimal efficacy and minimal toxicity for each patient, which has been termed personalized treatment. This review summarizes currently available predictive and prognostic chemosensitivity tests for metastatic CRC.

Acceptance of Chemo-prophylaxis for Latent Tuberculosis Infection among High School/College Student Contacts of Tuberculosis Patients in Shanghai, China

Student contacts of tuberculosis（TB）cases are susceptible to latent tuberculosis infection（LTBI）,and chemo-prophylaxis can reduce the risk of active TB among them.This study aimed to assess the acceptance of chemo-prophylaxis for LTBI among students, and their concerns regarding TB and its preventive treatment.

A chemo-mechanical model coupled with thermal effect on the hollow core–shell electrodes in lithium-ion batteries

Electrode is a key component to remain durability and safety of lithium-ion（Li-ion） batteries. Li-ion insertion/removal and thermal expansion mismatch may induce high stress in electrode during charging and discharging processes. In this paper, we present a continuum model based on COMSOL Multiphysics software, which involves thermal, chemical and mechanical behaviors of electrodes. The results show that,because of diffusion-induced stress and thermal mismatch, the electrode geometry plays an important role in diffusion kinetics of Li-ions. A higher local compressive stress results in a lower Li-ion concentration and thus a lower capacity when a particle is embedded another, which is in agreement with experimental observations.

Synthetic Smac Peptide Enhances Chemo-sensitivity of Bladder Cancer Cells

The effects of synthetic Smac peptide （SmacN7） on chemotherapeutic sensitivity of bladder cancer cells were investigated. SmacN7 penetratin peptide was synthesized and delivered into T24 cells. MTT assay was used to evaluate the viability of T24 cells induced by low-dosage of MMC Flow cytometry was used to analyze the proportions of apoptosis. Western blot was used to detect the expression of XIAP and Caspase-3. The activity of Caspase-3 was measured and the effect of SmacN7 combined with MMC on T24 cell lines was also determined. The results showed that SmacN7 penetratin peptide could successfully interact with endogenous XIAP, increase the proportions of apoptosis of T24 cell lines induced by low-dosage of MMC in a dose-and time-dependent manner. An obvious down-regulation of XIAP expression and up-regulation of Caspase-3 was identi-fied by Western blot. The activity of Caspase-3 in experimental group was significantly increased as compared with that in the control group. As compared with MMC group, the viability of T24 cells in SmacN7 penetratin peptide＋MMC group was markedly decreased to 2.22 and 3.61 folds at 24 h and 48 h respectively. It was concluded that SmacN7 penetratin peptide could act as a cell-permeable IAP inhibitor, inhibit the proliferation, induce apoptosis and enhance the chemo-sensitivity of bladder cancer cells to MMC. These findings indicate that SmacN7 penetratin peptide may be a very promising ageut for bladder cancer treatment when used in combination with chemotherapy.

Study of Chemical Etching and Chemo-Mechanical Polishing on CdZnTe Nuclear Detectors

Cadmium zinc telluride (CdZnTe) semiconductor has applications in the detection of X-rays and gamma-rays at room temperature without having to use a cooling system. Chemical etching and chemo-mechanical polishing are processes used to smoothen CdZnTe wafer during detector device fabrication. These processes reduce surface damages left after polishing the wafers. In this paper, we compare the effects of etching and chemo-mechanical polishing on CdZnTe nuclear detectors, using a solution of hydrogen bromide in hydrogen peroxide and ethylene glycol mixture. X-ray photoelectron spectroscopy (XPS) was used to monitor TeO2 on the wafer surfaces. Current-voltage and detector-response measurements were made to study the electrical properties and energy resolution. XPS results showed that the chemical etching process resulted in the formation of more TeO2 on the detector surfaces compared to chemo-mechanical polishing. The electrical resistivity of the detector is of the order of 1010 Ω-cm. The chemo-mechanical polishing process increased the leakage current more that chemical etching. For freshly treated surfaces, the etching process is more detrimental to the energy resolution compared to chemo-mechanically polishing.

Feasibility and oncological outcomes of laparoscopic rectal resection following neo-adjuvant chemo-radiotherapy: A systematic review

AIM: To study the feasibility and oncological outcomesfollowing laparoscopic total mesorectal excision(LTME) in patients who have received Neo-adjuvant long course chemo-radiotherapy(LCRT). METHODS: A protocol driven systematic review of published literature was undertaken to assess the feasibility and oncological outcomes following LTME in patients receiving LCRT. The feasibility was assessed using peri-operative outcomes and short term results. The oncological outcomes were assessed using local recurrence, disease free survival and overall survival.RESULTS: Only 8 studies-1 randomized controlled trial, 4 Case Matched/Controlled Studies and 3 Case Series were identified matching the search criteria. The conversion rate was low(1.2% to 28.1%), anastomotic leak rates were similar to open total mesorectal excision(0%-4.1% vs 0%-8.3%). Only 3 studies reported on local recurrence rates(5.2%-7.6%) at median 34 mo follow-up. A single study described disease free survival and overall survival at 3 years as 78.8% and 92.1% respectively. CONCLUSION: LTME following LCRT is feasible in experienced hands, with acceptable short term surgical outcomes and with the usual benefits associated with minimally invasive procedures. The long term oncological outcomes of LTME after LCRT appear to be comparable to open procedures but need further investigation.

Influence of Coupled Chemo-Mechanical Process on Corrosion Characteristics in Reinforcing Bars

We studied the corrosion characteristics of reinforcing bars in concrete under different corrosion conditions. The area-box （AB） value was used to classify the shape of pitting corrosion morphology in meso-scale, and fractographs of reinforcing bars with different corrosion morphology were discussed in micro- and macro-scales. The results show that the existence of the tensile stress affects the corrosion characteristics of reinforcing bars. The pitting morphology and fractograph of reinforcing bars exhibit a statistical fractal feature. The linear regression model fits the relationship between fractal dimensions of corrosion morphology and fractal dimension of fractograph fairly well. Using fractal dimension as the characterization parameter can not only reflect the characteristics of pitting corrosion morphology in reinforcing bars, but also reveal the fracture feature of corroded reinforcing bars.

Chemo-mechanical couplings in compacted argillite submitted to high-pH environment

In the French concept of deep nuclear wastes repository, the galleries should be backfilled with excavated argillite after the site exploitation period. After several thousands of years, the degradation of the concrete lining of the galleries will generate alkaline fluid (pH 】 12) that will diffuse through the backfill. The objective of the paper is to describe the influence of such solute diffusion on the microstructure and the mechanical behavior of compacted argillite. Saturated-portlandite water was circulated through compacted samples for 3, 6 and 12 months at 20 °C or 60 °C, respectively. The microstructures before and after fluid circulation were determined with mercury intrusion porosimetry. Since it was planned to introduce additives (bentonite or lime) in the remoulded argillite to backfill the deep galleries, such mixtures were also studied. The results show that the influence of the alkaline fluid on the properties of the argillite is a function of the nature of the additive. The pure argillite undergoes slight modifications that can be related to a limited dissolution of its clayey particles. Conversely, intense alteration of the bentonite-argillite mixture was observed. Lime addition improves the mechanical characteristics of the argillite through the precipitation of cementitious compounds.

Expression of X-linked Inhibitor of Apoptosis Protein and Its Effect on Chemotherapeutic Sensitivity of Bladder Carcinoma

The expression of X-linked inhibitor of apoptosis protein (XIAP) gene and its effect on chemotherapeutic sensitivity in bladder carcinoma was explored. By using immunohistochemistry, the expression of XIAP was detected in 47 bladder carcinomas and 5 normal bladder tissues. The XIAP gene was transfected into bladder cancer cell line T24 by liposome and the positive clone was screened by G418. Cellular XIAP mRNA level was detected by RT-PCR. Low-dose mitocycin C was administered to induce the apoptosis of T24 cells. The in vitro growth of bladder carcinoma cells was analyzed by MTT colorimetry, and the apoptosis rate was assayed by TUNEL methods. It was found XIAP was moderately expressed in bladder carcinomas with the the positive rate being 78.73% (37/47), but the positive rate was not correlated with carcinoma stages and grades (P<0.05). XIAP mRNA level in transfected T24 cells was significantly increased by 3.8 times as compared with that in the cells not transfected with XIAP. After treatment with low-dose mitomycin C (0.005 and 0.05 mg/mL), the growth rate in XIAP no-transfected control group was increased by (11.60±0.25)% and (16.51±0.87)% (P<0.05), and the apoptosis rate was decreased by (10.1±0.2)% and (11.9±0.2%) (P<0.05) respectively as compared with XIAP transfected group. It was concluded that XIAP was expressed in most of bladder carcimoma samples. Overexpression of XIAP in T24 could significantly reduce the MMC-induced apoptosis of bladder carcinoma, suggesting its effect on the chemothera- peutic sensitivity of T24 cells.

Analysis of Clinical Effect of Concurrent Chemo/radiotherapy in the Treatment of Advanced Cervical Cancer

The study aimed to analyze the efficacy and adverse effects of concurrent chemo/radiotherapy in the treatment of advanced cervical cancer,and the efficacy and safety of concurrent chemo/radiotherapy were evaluated to standardize the treatment.First of all,retrospective analysis was carried out,and 30 cases of advanced cervical cancer treated in hospitals from 2013 to 2018 were included in the study.30 cases of concurrent chemo/radiotherapy were included in the synchronous group,and 30 cases of radical radiotherapy alone were included in the radiotherapy group.The results showed that the CR rate and remission rate in the synchronous group were 43.3%and 93.3%,which were higher than those in the radiotherapy group(26.7%and 80.0%).The 3-year survival rate of the synchronous group was 80.0%,which was higher than that of the radiotherapy group,with a statistically significant difference(P<0.05).There was no significant difference in 3-year all-cause mortality,5-year survival and 5-year allcause mortality between the two groups.The tumor-free survival time in the synchronous group was(24.4±8.2)months,which was higher than that in the radiotherapy group(17.0±8.5)months,and the difference was statistically significant(P<0.05).Therefore,compared with radiotherapy alone,concurrent chemo/radiotherapy in the treatment of advanced cervical cancer can improve the 3-year survival rate and prolong the tumor-free survival time.However,it did not increase 5-year survival rate,and bone marrow suppression and gastrointestinal reactions were increased.

Conjugation of Magnetite Nanoparticles with Melanogenesis Substrate, NPrCAP Provides Melanoma Targeted, <i>in Situ</i>Peptide Vaccine Immunotherapy through HSP Production by Chemo-Thermotherapy

In order to develop melanoma-targeted in situ peptide vaccine immunotherapy, magnetite nanoparticles were conjugated with a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP). Magnetite nanoparticles introduced thermotherapy which caused non-apoptotic cell death and generation of heat shock protein (HSP) upon exposure to alternating magnetic field (AMF). NPrCAP was expected to develop a melanoma-targeted therapeutic drug because of its selective incorporation into melanoma cells and production of highly reactive free radicals, that result in not only oxidative stress but also apoptotic cell death by reacting with tyrosinase.

Does Chemo-Radiation Therapy Influence Outcomes in Unresectable Locally Advanced State IV Rectal Cancer?

Introduction: The median survival for patients with stage IV rectal cancer is approximately 20 months. Therapy should focus not only on improving survival but also on quality of life. The aim of our study was to determine if chemoradiation (C-RT) would improve palliation for metastatic unresectable locally advanced disease compared to patients receiving palliative chemotherapy alone (C) for stage IV cancer. Methods: Retrospective review of a prospectively maintained database at a single institution was carried out under IRB approval. From January 2004 to December 2008, 43 patients presenting with unresectable stage IV rectal cancer were identified with a median follow-up of 12 months. Patients with evidence of locally advanced disease or bulky disease received infusional 5-FU ± bevacizumab and 3D conformed mega voltage photon therapy (5400 cGy). Patients without evidence of bulky disease received either FOLFOX or FOLFIRI ± bevacizumab. Data on demographics, investigations, treatment, complications, metastasis, number of blood transfusions, days of hospitalization, and surgical intervention were analyzed using SPSS statistical software. p < 0.05 was considered statistically significant. Results: There were 25 and 18 patients in the C and C-RT groups respectively. There was no difference in mean age, sex or overall survival. Three patient (12%) in the C group developed hydronephrosis compared to 8 patients (44%) in the C-RT group (p < 0.05). Six patients (24%) developed bowel obstructions requiring an ostomy in the C group compared to 9 patient (50%) in the C-RT group (p = 0.07). In the C arm, 80% of patients required multiple hospitalizations for symptoms consistent with progression of disease compared to 61% of patients in the C-RT arm (p < 0.01). Conclusion: Chemoradiation in patients with locally advanced unresectable stage IV cancer has not been extensively investigated. At our institution, patients treated with C-RT for bulky stage IV rectal cancer required fewer hospitalizations when compared to those treated with chemotherapy alone.

Predictive value of ^(18)F-fluorodeoxyglucose PET/CT for transarterial chemolipiodolization of hepatocellular carcinoma

Myeong Jun Song,Si Hyun Bae,Chung-Hwa Park,Jeong Won Jang,Jong Young Choi,Seung Kew Yoon,Department of Internal Medicine,College of Medicine,The Catholic University of Korea,Seoul 137-040,South Korea Ie Ryung Yoo,Department of Nuclear,Medicine College of Medicine,The Catholic University of Korea,Seoul 137-040,South Korea Ho Jong Chun,Byung Gil Choi,Hae Giu Lee,Department of Radiology,College of Medicine,The Catholic University of Korea,Seoul 137-040,South

Multiple Chromatographic and Chemometric Methods for Quality Standardization of Chinese Herbal Medicines

Quality standardization of complementary medicine is fundamental for industry and practice as it underpins the quality,safety and efficacy of Chinese herbal medicines.Current herbal standardizations are often based on the quantitative analysis of a single compound,which may not reflect the total characteristic,bioactive and toxic nature of the herbs or products.Therefore,there is a need to establish an internationally recognized methodology for quality standardization of Chinese herbal medicines.The analytical methods reviewed in this article are pharmacognosy,TLC,HPLC,LCMS,CE and chemo-metrics.This article also covers the developments and applications of these methods in quality standardization.Recent advances show that a combination of these methods creates an overall chemical profile of each herb.This is supported by results reviewed in this article and obtained in our laboratory tests on medicinal herbs including Hypericum perforatum,Morinda officinalis and Centella asiatica.Significant variations in active components have been observed between herbal samples and products.It is proposed that the identification of active components,pharmacological activities and eventual clinical applications are required for a comprehensive quality standardization system.Our findings indicate that the combination of various chromatographic and chemometric methods will advance the methodology of quality standardization and enhance the overall confidence in herbal medicine for the health practitioner and the public.