Cardiac Manifestations with Chemotherapeutic Agents: 5 Fluorouracil-Induced Coronary Artery Vasospasm

5-fluorouracil (5-FU) is a fluorinated, pyrimidine analog, antineoplastic agent that is used in the treatment of several solid organ cancers. Cardiotoxicity is uncommon but life-threatening manifestations such as myocardial infarction may manifest owing to 5-FU-induced coronary artery spasm. Administering smaller doses of the drug, more frequently than not, decreases the risk of cardiotoxicity compared to large doses or with continuous infusions. We present a case of ST-segment elevation in a patient without known coronary artery disease who had presented following continuous 5-FU infusion. Coronary angiogram confirmed absence of coronary artery disease and intravenous calcium channel blockers administration was commensurate with the patient’s improvement in symptoms. We discuss the literature on 5-FU and its association with coronary artery spasm, and also briefly review chemotherapy-induced cardiotoxicities to help better prepare internists and other primary health care providers to face similar challenges, particularly of the uncommon but potentially life-threatening manifestations.

Reduction of Plasma MicroRNA-21 is Associated with Chemotherapeutic Response in Patients with Non-small Cell Lung Cancer

Objective： To examine plasma microRNA-21 （miR-21） level in patients with non-small cell lung cancer （NSCLC） and its potential correlation with chemotherapeutic response. Methods： 77 NSCLC patients and 36 age and sex-matched healthy controls were included. Plasma miR-21 concentration was examined using a quantitative real-time reverse transcription polymerase chain reaction assay （qRT-PCR）. Potential correlation between plasma mir-21 concentrations with chemotherapeutic responses was analyzed in 35 patients with advanced NSCLC （stages IIIB and IV）. Results： Plasma miR-21 was significantly higher in NSCLC patients relative to the healthy controls （P0.0001）. As a biomarker, plasma mir-21 had a receiver operating characteristic （ROC） curve area of 0.729 with 61.04% sensitivity and 83.33% specificity. Chemotherapeutic response in the 35 patients with advanced NSCLC （stages IIIB and IV） included partial response （PR） （n=11）, stable disease and progression disease （SD＋PD） （n=24）. The overall response rate （CR＋PR） was 31.4%. Plasma miR-21 in patients who achieved PR was significantly lower than those who did not respond （SD＋PD） （P=0.0487）, and comparable to that of the healthy controls （P=0.2744）. Conclusion： Plasma miR-21 is a good biomarker for NSCLC, and could be used to predict responses to chemotherapy.

The response of Golgi protein 73 to transcatheter arterial chemoembolization in patients with hepatocellular carcinoma may relate to the influence of certain chemotherapeutics

BACKGROUND： Golgi protein 73 （GP73） is a promising bio- marker of hepatocellular carcinoma （HCC）. It decreases after surgical resection, and resumes upon recurrence, indicating a potential indicator for the effectiveness of the treatment. But changes of GP73 after transcatheter arterial chemoemboliza- tion （TACE） have not been reported so far. This study was to investigate the dynamic changes of GP73 in HCC patients af- ter TACE treatment, and the possible underlying mechanisms in the cell cultures. METHODS： Blood samples were collected from 72 HCC pa- tients, before TACE, at day I and day 30 after TACE. GP73 lev- els were measured by Western blotting. The dynamic changes of GP73 were analyzed and compared with image changes and clinical data. The effects of chemotherapeutic agents （5-FU and pirarubicin） on GP73 expression were tested in three HCC cell lines （HepG2, HCCLM3 and MHCC97H）. RESULTS： The GP73 level was significantly elevated at day 1 and day 30 after TACE in HCC patients compared with that before the procedure （P〈0.05）. There was no statistical differ- ence between the two time points after TACE, nor correlationbetween GP73 levels and dinicopathological features, tumor metastasis, and patient survival. Pirarubicin, not 5-FU, signifi- cantly increased GP73 expression in three cell lines. CONCLUSIONS： Unlike surgical resection which decreases the GP73 level, TACE significantly increased GP73 expression in patients with HCC. No correlations were observed among GP73 levels, tumor characteristics and prognosis of patients with HCC.

Isolated Pelvic Hyperthermochemotherapeutic Perfusion-An Experimental Study on Isolating Efficacy

Hyperthermochemotherapeutic perfusion model through isolated pelvic vessels was developed to evaluate the leakage of hyperthermia and drugs (such as adriamycin) from the isolated pelvic circulation to systemic circulation and its associated side/toxic effects. The isolated pelvic circulation was perfused through a femoral artery catheter with hyperthermic (48 ℃ to 55 ℃) adriamycin solution (50 μg/ml) for 30 min. The efflux was drained through a femoral vein catheter. And the pelvic temperature was kept at the level of 43±0.5 ℃. The temperature of pelvic circulation was kept at 4 ℃ to 5 ℃ greater than the systemic/core temperature. The adriamycin concentration of pelvic efflux was 12 to 46 folds of that of systemic serum. The difference between them was very significant ( P <0.001). As the perfusion pressure was increased, which kept lower than the mean systemic artery pressure, the leakage of the adriamycin from the isolated pelvic circulation to systemic circulation was increased, but there was no significant difference between them ( P >0.05). During isolated perfusion, the systemic blood dynamics remained stable and there were no organic injuries on the important organs. It was suggested that the isolating efficacy of the modality of isolated pelvic hyperthermochemotherapeutic perfusion through vessels was rather high. The hyperthermia and drugs could be effectively limited in the isolated pelvic region with minor side effects on the systemic circulation and important organs.

Can inhibition of telomerase increase pancreatic cancer cell's susceptibility to chemotherapeutic reagents?

Objectives: To clarify the inhibition of pancreatic can-cer cells by interference with the hTR component of thetelomerase reverse transcriptase enzymatic complexand evaluate susceptibility of antisense hTR pancreaticcancer cells to chemotherapeutic reagents.Methods: A 593 bp of full length hTR cDNA was sub-cloned into a mammalian expression vector pcDNA3.1(-) in antisense orientation to construct an antisensehTR expression plasmid. The plasmids were introducedinto Pancl cells, a human pancreatic carcinoma cellline, by lipofectin, and G418-resistant stable trans-formants were expanded. Resulting stable clones werescreened for the presence of hTR insert by PCR withT7 and BGH reverse primers located on the flanks ofthe multiclonal site of pcDNA3.1 vector. Cell growth rate,hTR expression, telomerase activity, and anchorage-in-dependent growth property were analyzed. Finally, sus-ceptibility of antisense hTR cells to chemotherapeuticreagents was evaluated.Results: Significant downregulation of endogenous hTRwas evident in the antisense-hTR transformed cells,and telomerase activity was markedly decreased com-pared to control cells in standard TRAP assays. Fur-thermore, the proliferation and the anchorage-inde-pendent growth ability in antisense-hTR expressingcells were significantly decreased compared with thecontrol parental cells. However, no crisis or senescencephenomena was observed. Antisense hTR appears toincrease Pancl cell's susceptibility to chemotherapeuticreagent cDDP, but not to differentiation reagent DM-SO, COX2 inhibitor sulinbac, NS-398, curcumin, andchemotherapeutic reagent adriamycin(ADM).Conclusions: These data indicate that hTR is probablya critical component of human telomerase activity andthat downregulation of the RNA component of humantelomerase is an effective target for anticancer strategyand antisense hTR can increase Pancl cell's susceptibilityto cDDP.

Evaluation of the Effect of Chemotherapeutic Drug Training on Mobile Terminal for Neuro-Oncology Nurses Based on Kirkpatrick’s Model

Background: Since there has been training, there has been discussion about the effect of training. But training evaluation is not systematic until Kirkpatrick came up with the training evaluation model in 1959. At present, the prevailing model in the systematic summary of training evaluation is still The Kirkpatrick’s model. This model was further improved in 1994, more responsive to contemporary needs, and thus widely used all over the world. At the beginning, it was widely used in human resource management of enterprises. In recent years, this model has been gradually used in the medical field to evaluate the effect of medical training. The Kirkpatrick’s model has a systematic, integrated and persuasive evaluation system for trainees. It has good effects in the pre-service nurse training, the professional image and code of conduct nurses training, and the geriatric nurse training. At present, there are few studies on the chemotherapeutic drug training of neurologist nurses in China. In clinical work, nurses’ cognitive and practical behaviors of chemotherapeutic drug protection and drug extravasation prevention and treatment are insufficient. It directly harms the health of nursing staff and increases the complications of chemotherapy, increases pain of tumor patients, delays or interrupts chemotherapy, and aggravates the economic burden of patients. Especially, Chemotherapeutic drugs for neuro-oncology have particularity and necessity of urgent training. Objective: To investigate the effect of chemotherapeutic drug training through mobile terminal for neuro-oncology nurses based on the Kirkpatrick’s model. Methods: The training content and evaluation questionnaire for chemotherapeutic drugs were designed by nursing management personnel and senior nurses in our department according to the guidelines and common diseases requiring chemotherapy in the department. The content includes the basic knowledge of neuro-oncology chemotherapy, pharmacological knowledge, toxic and side effect of chemotherapy, etc., which are regularly pushed through the mobile terminal-WeChat. Forty nurses participated in the training and the effect is evaluated by Kirkpatrick’s model. Result: After the training, 100% of nurses were satisfied with the training content and 97.5% with the training form. The scores of nurses in learning level such as basic pharmacological knowledge, drug configuration and exposure, drug treatment and infusion, observation of toxic and side effects, and treatment of drug extravasation were significantly higher than those before the training (P < 0.01). The scores of nurses in the behavior level such as drug allocation, health education, toxic and side effect observation and prediction, treatment of exosmosis, occupational protection were significantly higher than those before the training. After the training, the satisfaction of managers, chemotherapy physicians and chemotherapy patients on the behavior of nurses was significantly higher than that before the training (P < 0.01). Conclusion: The chemotherapeutic drug training through mobile terminal based on Kirkpatrick’s model can improve the ability of neuro-oncology nurses, so as to improve the satisfaction of physicians and patients.

Photosensitive pro-drug nanoassemblies harboring a chemotherapeutic dormancy function potentiates cancer immunotherapy

Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment.However,developing multifunctional biodegradable,biocompatible,low-toxic but highly efficient,and clinically available transformed nano-immunostimulants remains a challenge and is in great demand.Herein,we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components-a self-assembled natural small molecule betulinic acid(BA),a water-soluble chitosan oligosaccharide(COS),and a low toxic photosensitizer chlorin e6(Ce6)-to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer immunotherapy.We show that the designed nanodrugs harbored a smart and distinctive“dormancy”characteristic in chemotherapeutic effect with desired lower cytotoxicity,and multiple favorable therapeutic features including improved^(1)O_(2)generation induced by the reduced energy gap of Ce6,pH-responsiveness,good biodegradability,and biocompatibility,ensuring a highly efficient,synergistic photochemotherapy.Moreover,when combined with anti-PD-L1 therapy,both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy(PDT)could effectively activate antitumor immunity when treating primary or distant tumors,opening up potentially attractive possibilities for clinical immunotherapy.

Dexamethasone and N-acetylcysteine before transarterial chemoembolization in hepatocellular carcinoma:A Western perspective

Post-embolization syndrome(PES)is the most common complication in patients with hepatocellular carcinoma treated with transarterial chemoembolization.Many strategies have been evaluated to reduce the incidence of PES,but no standard prevention guidelines currently exist.In a single-center,placebo-controlled trial,Simasingha et al evaluated the prophylactic administration of a combination of dexamethasone and N-acetylcysteine and documented a significant reduction in the incidence of PES(from 80%to 6%),of post-procedural liver decompensation(from 14%to 0%),and a shorter hospital stay(4 days vs 6 days),alongside an acceptable safety profile.The results of this study raise several controversial points regarding their applicability in the Western world.In the West,there is a greater and increasing prevalence of metabolic and alcoholic etiologies of liver cirrhosis,so a not negligible number of patients with type II diabetes or hypertension would be excluded from high-dosage dexamethasone prophylaxis.Furthermore,in the West,there is a preferred use of drug-eluting beads loaded with doxorubicin,which are associated with a lower incidence of PES.A study on prophylaxis with dexamethasone and/or N-acetylcysteine in a Western population is hopefully awaited.

Current landscape of preoperative neoadjuvant therapies for initial resectable colorectal cancer liver metastasis

Colorectal cancer liver metastasis(CRLM)presents a clinical challenge,and optimizing treatment strategies is crucial for improving patient outcomes.Surgical resection,a key element in achieving prolonged survival,is often linked to a heightened risk of recurrence.Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases,this approach has gained attention for its role in tumor downsizing,assessing biological behavior,and reducing the risk of postoperative recurrence.However,the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates.The balance between tumor reduction and the risk of hepatic injury,coupled with concerns about delaying surgery,necessitates a nuanced approach.This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases.Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion.Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative.The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing,such as RAS/BRAF and PIK3CA,in tailoring neoadjuvant regimens.Furthermore,the review emphasizes the need for a multidisciplinary approach to navigate the comp-lexities of CRLM.Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies.The management of progression following neoadjuvant chemotherapy requires a tailored approach,acknowledging the diverse biological behaviors that may emerge.In conclusion,this review aims to provide a comprehensive perspective on the considerations,challenges,and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM.By combining evidencebased insights with practical experiences,we aspire to contribute to the ongoing discourse on refining treatment paradigms for improved outcomes in patients with CRLM.

Adult rhabdomyosarcoma combined with acute myeloid leukemia: A case report

BACKGROUND Rhabdomyosarcoma is a tumor of mesenchymal origin.Secondary leukemia is a complication of previous transformation to other hematologic disorders or is a treatment-related acute myeloid leukemia secondary to cytotoxic chemotherapy or radiation therapy for other malignancies.CASE SUMMARY We present the case of a 36-year-old female patient who was diagnosed with rhabdomyosarcoma and acute myeloid leukemia.Further disease progression was observed after multiline chemotherapy.Eventually,the patient suffered cerebral hemorrhage,which resulted in death.CONCLUSION The incidence of rhabdomyosarcoma in adults is extremely low,and secondary leukemia caused by rhabdomyosarcoma is even rarer.Secondary leukemia has a very poor prognosis and a low overall survival rate.

Monomorphic epitheliotropic intestinal T-cell lymphoma with bone marrow involved: A case report

BACKGROUND Monomorphic epithelial intestinal T-cell lymphoma(MEITL)is a rare type of peripheral T-cell lymphoma.The clinical manifestations are diarrhea,abdominal pain,perforation and an abdominal mass.CASE SUMMARY We present a 52-year-old female patient who was diagnosed with MEITL.Further disease progression was observed after multiline chemotherapy.Eventually,the patient died of a severe infection.CONCLUSION MEITL is a rare intestinal primary T-cell lymphoma with aggressive behavior,a high risk of severe life-threatening complications,and a poor prognosis.

Britanin–a beacon of hope against gastrointestinal tumors?

Britanin is a bioactive sesquiterpene lactone known for its potent anti-inflammatory and anti-oxidant properties.It also exhibits significant anti-tumor activity,suppressing tumor growth in vitro and in vivo.The current body of research on Britanin includes thirty papers predominantly related to neoplasms,the majority of which are gastrointestinal tumors that have not been summarized before.To drive academic debate,the present paper reviews the available research on Britanin in gastrointestinal tumors.It also outlines novel research directions using data not directly concerned with the digestive system,but which could be adopted in future gastrointestinal research.Britanin was found to counteract liver,colorectal,pancreatic,and gastric tumors,by regulating proliferation,apoptosis,autophagy,immune response,migration,and angiogenesis.As confirmed in pancreatic,gastric,and liver cancer,its most commonly noted molecular effects include nuclear factor kappa B and B-cell lymphoma 2 downregulation,as well as Bcl-2-associated X protein upregulation.Moreover,it has been found to induce the Akt kinase and Forkhead box O1 axis,activate the AMP-activated protein kinase pathway,elevate interleukin-2 and peroxisome proliferator-activated receptor-γlevels,reduce interleukin-10,as well as downregulate matrix metalloproteinase-9,Twist family bHLH transcription factor 1,and cyclooxygenase-2.It also inhibits Myc–HIF1αinteraction and programmed death ligand 1 transcription by interrupting the Ras/RAF/MEK/ERK pathway and mTOR/P70S6K/4EBP1 signaling.Future research should aim to unravel the link between Britanin and acetylcholinesterase,mast cells,osteolysis,and ischemia,as compelling data have been provided by studies outside the gastrointestinal context.Since the cytotoxicity of Britanin on noncancerous cells is significantly lower than that on tumor cells,while still being effective against the latter,further in-depth studies with the use of animal models are merited.The compound exhibits pleiotropic biological activity and offers considerable promise as an anti-cancer agent,which may address the current paucity of treatment options and high mortality rate among patients with gastrointestinal tumors.

Nanocarrier-mediated co-delivery of chemotherapeutic drugs and gene agents for cancer treatment

The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells,which is usually caused by abnormal gene expression.RNA interference mediated by si RNA and mi RNA can selectively knock down the carcinogenic genes by targeting specific m RNAs.Therefore,combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer therapy.Due to poor stability and solubility associated with gene agents and drugs,suitable protective carriers are needed and have been widely researched for the co-delivery.In this review,we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents,as well as the advances in co-delivery systems.

Low dosages:new chemotherapeutic weapons on the battlefield of immune-related disease

Chemotherapeutic drugs eliminate tumor cells at relatively high doses and are considered weapons against tumors in clinics and hospitals.However,despite their ability to induce cellular apoptosis,chemotherapeutic drugs should probably be regarded more as a class of cell regulators than cell killers,if the dosage used and the fact that their targets are involved in basic molecular events are considered.Unfortunately,the regulatory properties of chemotherapeutic drugs are usually hidden or masked by the massive cell death induced by high doses.Recent evidence has begun to suggest that low dosages of chemotherapeutic drugs might profoundly regulate various intracellular aspects of normal cells,especially immune cells.Here,we discuss the immune regulatory roles of three kinds of chemotherapeutic drugs under low-dose conditions and propose low dosages as potential new chemotherapeutic weapons on the battlefield of immune-related disease.

EFFECTS OF TNF ALONE OR IN COMBINATION WITH CHEMOTHERAPEUTIC AGENTS ON HUMAN OVARIAN CANCERS IN VITRO AND IN NUDE MICE

Using the tetrazolium (MTT) assay, we examined the cytotoxicities of recombinant human tumor necrosis factor (rhTNF) and five chemotherapeutic agents, namely CTX, 5-FU, VCR, DDP and KSM, on human ovarian cancer cell lines OVCAR3 and CAOV3. The results showed that the cytotoxicities of rhTNF at concentrations of 50-50 000 U / ml on OVCAR3 cell line and CAOV3 cell line exposed to rhTNF for 24 hours were from 14.2% ± 6.8% to 67.2%± 3.0% and from 8.2%± 4.3% to 60.9%±1.3%, respectively. The cytotoxicities of all five chemotherapeutic agents tested on the two cell lines were much lower than that of rhTNF. We also studied the combined antitumor potential of rhTNF with the five chemotherapeutic agents and the results showed that there were various degrees of synergism in cytotoxicities of rhTNF in combination with DDP or KSM on the two cell lines. Based on experiments in vitro, the in vivo antitumor activities of rhTNF, both alone and in combination with KSM, were examined in OVCAR3 cancer transplanted in nude mice. The results showed a considerable antitumor effect of rhTNF when it was used alone and a marked synergistic effect when it was used in combination with KSM on the xenograft tumors.

喜辽妥联合硫酸镁湿敷在血液肿瘤患儿化疗性静脉炎中的应用效果探究

目的:探讨喜辽妥联合硫酸镁湿敷治疗血液肿瘤患儿化疗性静脉炎的临床效果。方法:选择2015年1—2016年10月我院儿科收治的90例因血液肿瘤化疗而放置留置针的患儿。按随机数字表法分为观察组和对照组,各45例。在放置留置针的过程中,对照组予硫酸镁湿敷,观察组联合应用硫酸镁湿敷和喜辽妥软膏。比较两组静脉炎发生率,发生静脉炎患儿的治愈时间,以及患儿在治疗过程中的舒适度。结果:观察组静脉炎发生率低于对照组,差异有统计学意义(P<0.05);在发生静脉炎后,观察组缓解时间短于对照组,差异有统计学意义(P<0.05);对于整个治疗过程中的舒适程度评价,观察组评分高于对照组,差异有统计学意义(P<0.05)。结论:喜辽妥联合硫酸镁湿敷能够有效预防化疗性静脉炎的发生,提高患儿在放置留置针期间的舒适度,并能在较短时间内治愈静脉炎,具有较高的临床应用价值。

Long interspersed nuclear element ORF-1 protein promotes proliferation and resistance to chemotherapy in hepatocellular carcinoma

AIM:To clarify the specific roles and mechanisms of long interspersed nuclear element-1 ORF-1 protein [human long interspersed nuclear element-1(LINE-1),ORF-1p] in chemotherapeutic drug resistance and cell proliferation regulation in hepatocellular carcinoma(HCC) cells.METHODS:MTT assays were performed to identify the effect of the chemotherapeutic drug toxicity on HepG2 cells.Cell proliferation inhibition and the IC 50 were calculated by the Origin 8.0 software.Western blotting assays were performed to investigate whether LINE-1 ORF-1p modulates the expression of some important genes,including p53,p27,p15,Bcl-2,mdr,and p-gp.To corroborate the proliferation and anchor-independent growth results,the HepG2 cells were analyzed by flow cytometry to investigate the effect of LINE-1 ORF1p on the apoptosis regulation.RESULTS:LINE-1 ORF-1p contributed to the resistance to several chemotherapeutic drugs(cisplatin and epirubicin) in HepG2 cells.The IC 50 of the epirubicin and cisplatin increased from 36.04 nmol/L to 59.11 nmol/L or from 37.94 nmol/L to 119.32 nmol/L.Repression of LINE-1 ORF-1p expression by the siRNA could markedly enhance the response of HepG2 cells to the epirubicin and cisplatin.The IC 50 correspondingly decreased from 28.06 nmol/L to 3.83 nmol/L or from 32.04 nmol/L to 2.89 nmol/L.Interestingly,down-regulation of LINE-1 ORF-1p level by siRNA could promote the response of HepG2 cells to the paclitaxel.The IC 50 decreased from 35.90 nmol/L to 7.36 nmol/L.However,overexpression of LINE-1 ORF-1p did not modulate the paclitaxel toxicity in HepG2 cells.Further Western blotting revealed that LINE-1 ORF-1p enhanced mdr and p-gp gene expression.As a protein arrested in the nucleus,LINE-1 ORF-1p may function through modulating transcriptional activity of some important transcription factors.Indeed,LINE-1 ORF-1p promoted HepG2 cell proliferation,anchor-independent growth and protected the cells against apoptosis through modulating the expression of p15,p21,p53,and Bcl-2 genes.CONCLUSION:LINE-1 ORF-1p promotes HepG2 cell proliferation and plays an important role in the resistance of chemotherapeutic drugs.By establishing novel roles and defining the mechanisms of LINE-1 ORF1p in HCC chemotherapeutic drug resistance and cell proliferation regulation,this study indicates that LINE-1 ORF-1p is a potential target for overcoming HCC chemotherapeutic resistance.

Cerebral lipiodol embolism following transcatheter arterial chemoembolization for hepatocellular carcinoma

Cerebral lipiodol embolism (CLE) is an extremely rare complication of transcatheter arterial chemoembolization for hepatocellular carcinoma (HCC). The authors present a case of CLE that occurred after the second hepatic arterial chemoembolization for HCC, and attempt to introduce several plausible mechanisms of CLE, after reporting the clinical and radiological findings and reviewing the medical literature.

The 150 most important questions in cancer research and clinical oncology series:questions 50-56

Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology, which sparkle diverse thoughts, interesting communications, and potential collaborations among researchers all over the world. In this article, seven more questions are presented as followed. Question50. When tumor cells spread from primary site to distant sites, are they required to be "trained" or "armed" in the bone marrow niche prior to colonizing soft tissues? Question 51. Are there tipping points during cancer progression which can be identified for manipulation? Question 52. Can we replace molecular biomarkers by network biomarkers?Question 53. Are conventional inhibitors of key cellular processes such as cell proliferation and differentiation more effective than targeted chemotherapeutics that antagonize the downstream cell signaling network via cell-surface receptors such as epidermal growth factor receptor(EGFR), vascular endothelial growth factor receptor(VEGFR) and c-Met, or intracellular receptors such as androgen receptor(AR) and estrogen receptor(ER), by drugs like erlotinib,sunitinib and cabozantinib, or enzalutamide and tomoxifen? Question 54. How can we robustly identify the candidate causal event of somatic genome alteration(SGA) by using computational approach? Question 55. How can we systematically reveal the immune evasion mechanism exploited by each tumor and utilize such information to guide targeted therapy to restore immune sensitivity? Question 56. Can the nasopharyngeal carcinoma(NPC) patients with sarcomatoid carcinoma(SC) subtype benefit from more specific targeted therapy?

Curcumin cytotoxicity is enhanced by PTEN disruption in colorectal cancer cells

AIM:To investigate the effects of phosphatase and tensin homolog deleted on chromosome 10(PTEN) deficiency on the cytotoxicity of chemotherapeutic agents toward colorectal cancer cells.METHODS:PTEN-deficient colorectal cancer(CRC) cells were generated by human somatic cell gene targeting using the adeno-associated virus system. The cytotoxic effects of compounds including curcumin,5-fluorouracil(5-FU),dihydroartemisinin(DHA),irinotecan(CPT-11)and oxaliplatin(OXA) on cancer cells were determined using the MTT assay. Enhanced cytotoxicity of curcumin in PTEN-deficient CRC cells was observed,and this was confirmed using clonogenic assays. Apoptosis and cell cycle progression were analyzed by flow cytometry.Levels of apoptosis and cell cycle-related proteins were examined by Western blotting.RESULTS:We developed an isogenic set of CRC cell lines that differed only in their PTEN status. Using this set of cell lines,we found that disruption of the PTEN gene had no effect on the sensitivity of CRC cells to5-FU,CPT-11,DHA,or OXA,whereas PTEN disruption increased the sensitivity of CRC cells to curcumin. Loss of PTEN did not alter the curcumin-induced apoptosis in CRC cells. However,PTEN deficiency led to an altered pattern of curcumin-mediated cell cycle arrest.In HCT116 PTEN+/+cells,curcumin caused a G2/M phase arrest,whereas it caused a G0/G1 phase arrest in HCT116 PTEN-/-cells. Levels of cell cycle-related proteins were consistent with these respective patterns of cell cycle arrest.CONCLUSION:Curcumin shows enhanced cytotoxicity toward PTEN-deficient cancer cells,suggesting that it might be a potential chemotherapeutic agent for cancers harboring PTEN mutations.