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 effec...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.展开更多
AIM： To study the inhibitory effects of Fuzheng Yiliuyin （Decoction for Suppressing Tumors by Strengthening the Body Resistance） in combination with chemotherapeutics on human gastric carcinoma cell strain. METHODS...AIM： To study the inhibitory effects of Fuzheng Yiliuyin （Decoction for Suppressing Tumors by Strengthening the Body Resistance） in combination with chemotherapeutics on human gastric carcinoma cell strain. METHODS： Fuzheng Yiliuyin （ZY） combined with various kinds of chemotherapeutics was put into two kinds of cultivated human gastric carcinoma cell strains, then its inhibitory effects on human gastric carcinoma cell strains were determind by the MTT method. Flow cytorneter was used to assay the apoptosis rate, and the ultrastructure of gastric carcinoma cells was observed under transmission electron microscope. RESULTS： Obvious apoptosis was seen in gastric carcinoma cells after treatment with ZY for 72 h. ZY and chemical drugs had synergistic inhibition effects on the cultivated gastric carcinoma cells, but the effects were different on various cell strains. The inhibitory effects of ZY could be strengthened by cytotoxic action and apoptosis. ZY combined with tluorouracil, etoposide and cisplatin （EFP） chemotherapeutics had better inhibitory effects on SGC-7901, while ZY combined with EFP or with DDP chemotherapeutics had better inhibitory effects than other drugs on MGC-803. CONCLUSION： ZY induces apoptosis and inhibits the growth of gastric carcinoma cells. ZY has the synergistic function of chemotherapeutics.展开更多
Cancer is characterized by abnormal cell growth and remains a leading global cause of death despite advances in conventional therapies.Limitations such as lack of selectivity,cytotoxic side effects,and multidrug resis...Cancer is characterized by abnormal cell growth and remains a leading global cause of death despite advances in conventional therapies.Limitations such as lack of selectivity,cytotoxic side effects,and multidrug resistance underscore the need for potent anticancer agents.TopoisomeraseⅡ(TOP2)has emerged as a pivotal target for anticancer drugs,categorized as poisons and catalytic inhibitors.While clinically used TOP2-based drugs predominantly act as poisons,concerns regarding their cytotoxicity and DNA-damaging potential persist.In response to these challenges,exploring natural bioactive compounds(NBCs),including small molecules from Chinese herbs,as sources of novel anticancer agents has become a focal point in pharmaceutical research.Recognizing that NBCs alone may not satisfy as anticancer agents,this review aims to comprehensively analyze the current published studies,specifically focusing on the combined applications of TOP2-inhibiting approved chemotherapeutics and natural products.The review explores this approach's potential synergies and challenges,emphasizing the importance of developing effective and targeted anticancer strategies.展开更多
Paclitaxel(PTX),a valuable natural product derived from Taxus species,exhibits remarkable anti-cancer properties.It penetrates nanopores in microtubule walls,interacting with tubulin on the lumen surface and disruptin...Paclitaxel(PTX),a valuable natural product derived from Taxus species,exhibits remarkable anti-cancer properties.It penetrates nanopores in microtubule walls,interacting with tubulin on the lumen surface and disrupting microtubule dynamics,thereby inducing cytotoxic effects in cancer cells.PTX and its derivatives have gained approval for treating various diseases due to their low toxicity,high efficiency,and broad-spectrum application.The widespread success and expanding applications of PTX have led to increased demand,raising concerns about accessibility.Consequently,researchers globally have focused on developing alternative production methods and applying nanocarriers in PTX delivery systems to enhance bioavailability.This review examines the challenges and advancements in PTX sourcing,production,physicochemical properties,anti-cancer mechanisms,clinical applications,trials,and chemo-immunotherapy.It aims to provide a comprehensive reference for the rational development and effective utilization of PTX.展开更多
Chemotherapeutic drugs such as doxorubicin(DOx)and oxaliplatin can induce immunogenic cell death(ICD)in tumor cells.Current studies have demonstrated that peptide-based drugs can also induce ICD in tumor cells.Unlike ...Chemotherapeutic drugs such as doxorubicin(DOx)and oxaliplatin can induce immunogenic cell death(ICD)in tumor cells.Current studies have demonstrated that peptide-based drugs can also induce ICD in tumor cells.Unlike small molecule drugs,peptide drugs not only enhance the effectiveness of immunotherapy but also offer the advantage of low biotoxicity[1].展开更多
Osteosarcoma(OS)is the most frequent primary bone sarcomas with high recurrence and poor prognosis.Emerging evidence indicates that membraneless organelles stress granules(SGs),whose assemblies are driven by scaffold ...Osteosarcoma(OS)is the most frequent primary bone sarcomas with high recurrence and poor prognosis.Emerging evidence indicates that membraneless organelles stress granules(SGs),whose assemblies are driven by scaffold protein G3BP1,are extensively involved in tumor,especially in OS.However,how SGs behave and communicate with organelles,particularly nucleoli and mitochondria,during drug challenges remain unknown.This study revealed that chemotherapeutic drugs activated the cysteine protease asparagine endopeptidase(AEP)to specifically cleave the SG core protein G3BP1 at N258/N309 in OS and malignant glioma.tG3BP1-Ns modulated SG dynamics by competitively binding to full-length G3BP1.Strikingly,tG3BP1-Cs,containing a conserved RNA recognition motif CCUBSCUS,sequestered mRNAs of ribosomal proteins and oxidative phosphorylation genes in the nucleoli and mitochondria to repress translation and oxidative stress.Moreover,the inhibition of AEP promoted the tumor-suppressing effect of chemotherapeutic drugs,whereas AEP-cleaved G3BP1 rescue reversed the effect in both OS and glioma models.Cancerous tissues exhibited high levels of AEP and G3BP1 truncations,which were strongly associated with poor prognosis.展开更多
Background:Breast cancer still stands to be the foremost contributor to cancer-related incidence and mortality in women globally accounting for about 14%of all female cancer-related deaths worldwide.This research seek...Background:Breast cancer still stands to be the foremost contributor to cancer-related incidence and mortality in women globally accounting for about 14%of all female cancer-related deaths worldwide.This research seeks to illustrate the mechanisms and clinical findings of natural products against breast cancer treatment.Methodology:Required data for this review article was retrieved employing several readily obtainable search databases,including Web of Science■(Thomson Reuters,USA),PubMed■(U.S.National Library of Medicine,USA),and SciVerse Scopus■(Elsevier Properties S.A.,USA),taking into consideration certain search terms like“breast cancer,”“natural products against breast cancer,”and“Clinically proven natural products in the treatment of breast cancer”and so on.Results:Several natural products,namely Omega-3 fatty acids,dietary isothiocyanates,curcumin,green tea,flaxseed,limonene,and others,were found to modulate crucial pathways in breast cancer cells.These substances suppressed angiogenesis by downregulating the vascular endothelial growth factor(VEGF),promoted apoptosis by activating caspase enzymes,and prevented cell proliferation by controlling cyclin-dependent kinases.Clinical studies demonstrated improved outcomes in patients receiving these natural products with standard treatment procedures.Discussion:The findings underscore the multifaceted functions of natural products in breast cancer therapy,highlighting their potential to increase the efficacy of conventional treatments while reducing adverse effects.Further exploration of synergistic actions and optimal dosages is needed.Conclusion:Clinically proven natural products represent a potential avenue for breast cancer treatment with their mechanistic insights that facilitate their incorporation into treatment regimens.To maximize clinical applications,future inquiries should center on elucidating the full spectrum of these anticancer functions.展开更多
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 ...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?展开更多
Despite advancements in the areas of omics and chemoinformatics,potent novel biotherapeutic molecules with new modes of actions are needed for leishmaniasis.The socioeconomic burden of leishmaniasis remains alarming i...Despite advancements in the areas of omics and chemoinformatics,potent novel biotherapeutic molecules with new modes of actions are needed for leishmaniasis.The socioeconomic burden of leishmaniasis remains alarming in endemic regions.Currently,reports from existing endemic areas such as Nepal,Iran,Brazil,India,Sudan and Afghanistan,as well as newly affected countries such as Peru,Bolivia and Somalia indicate concerns of chemoresistance to the classical antimonial treatment.As a result,effective antileishmanial agents which are safe and affordable are urgently needed.Natural products from both flora and fauna have contributed immensely to chemotherapeutics and serve as vital sources of new chemical agents.This review focuses on a systematic cross-sectional view of all characterized anti-leishmanial compounds from natural sources over the last decade.Furthermore,IC_(50)/EC_(50),cytotoxicity and suggested mechanisms of action of some of these natural products are provided.The natural product classification includes alkaloids,terpenes,terpenoids,and phenolics.The plethora of reported mechanisms involve calcium channel inhibition,immunomodulation and apoptosis.Making avail-able enriched data pertaining to bioactivity and mechanisms of natural products complement current efforts geared towards unraveling potent leishmanicides of therapeutic relevance.展开更多
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...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.展开更多
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...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.展开更多
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 curre...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.展开更多
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 proliferati...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.展开更多
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...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.展开更多
AIM: To investigate the combination effect of hTERT antisense oligonucleotide 'Cantide' and three chemotherapeutic drugs (cisplatin, 5-fluorouracil (5-FU) and adriamycin (ADM)) on inhibiting the proliferation ...AIM: To investigate the combination effect of hTERT antisense oligonucleotide 'Cantide' and three chemotherapeutic drugs (cisplatin, 5-fluorouracil (5-FU) and adriamycin (ADM)) on inhibiting the proliferation of HepG2, BGC and A549 cell lines in vitro, and to investigate the efficacy of Cantide used in combination with cisplatin (DDP) in vivo. METHODS: Cantide was transfected into these tumor cells by Lipofectin, and cell growth activity was calculated by microcytotoxicity assay. In vivo study, cells of HepG2 were implanted in Balb/c nude mice for 4 d. Then Cantide, DDP and Cantide+DDP were given intra peritonea Ily for 24 d respectively. The body weights of the tumor-bearing animals and their tumor mass were measured later to assess the effect of combination therapy in the nude mice. To evaluate the interaction of Cantide and these chemotherapeutic drugs, SAS software and Jin Zhengjun method were used. RESULTS: Combination treatments with 0.1μmol/L Cantide reduced the IC50 of DDP, 5-FU and ADM from 1.07, 4.15 and 0.29 μg/mL to 0.25,1.52 and 0.12 μg/mL respectively. The inhibition ability of DDP, 5-FU and ADM respectively in combination with Cantide in these tumor cells was higher than that of these drugs alone (P<0.0001). And synergism (Q≥1.15)was observed at the lower concentration of DDP (≤1μg/mL) and ADM (≤0.1 μg/mL) with combination of Cantide. In vivo, combination treatment with Cantide and DDP produced the greater growth inhibition of human liver carcinoma cells HepG2 in nude mice (0.65±0.19 g tumor) compared with that when only one of these drugs was used (Cantide group: 1.05±0.16 g tumor, P= 0.0009<0.001; DDP group: 1.13±0.09 g tumor, P= 0.0001<0.001). CONCLUSION: These findings indicate that Cantide may enhance therapeutic effectiveness of chemotherapeutic drugs over a wide range of tumor cells in vitro, and the combination use of Cantide and DDP can produce much higher inhibition rates, as compared with when either of these drugs was used only in vivo.展开更多
AIM: To study the effect of a number of chemotherapeutic drugs on five human intrahepatic cholangiocarcinoma (CCA) cell lines. The expressions of genes that have been proposed to influence the resistance of chemothera...AIM: To study the effect of a number of chemotherapeutic drugs on five human intrahepatic cholangiocarcinoma (CCA) cell lines. The expressions of genes that have been proposed to influence the resistance of chemotherapeutic drugs including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), glutathione-S-transferase PI (GSTP1), multidrug resistance protein (MDR1) and multidrug resistance-associated proteins (MRPs) were also determined. METHODS: Five human CCA cell lines (KKU-100, KKU-M055, KKU-M156, KKU-M214 and KKU-OCA17) were treated with various chemotherapeutic drugs and growth inhibition was determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Semi-quantitative levels of gene expression were determined by a reverse transcriptase polymerase chain reaction (RT-PCR). Results of IC_(50) values and the ratios of gene expression were analyzed by linear regression to predict their relationship. RESULTS: Among five CCA cell lines, KKU-M055 was the most sensitive cell line towards all chemotherapeutic drugs investigated, particularly taxane derivatives with IC_(50) values of 0.02-3 nmol/L, whereas KKU-100 was apparently the least sensitive cell line. When compared to other chemotherapeutic agents, doxorubicin and pirarubicin showed the lowest IC_(50) values (＜5 μmol/L) in all five CCA cell lines. Results from RT-PCR showed that TS, MRP1, MRP3 and GSTP1 were highly expressed in these five CCA cell lines while DPD and MRP2 were only moderately expressed. It should be noted that MDR1 expression was detected only in KKU-OCA17 cell lines. A strong correlation was only found between the level of MRP3 expression and the IC_(50) values of etoposide, doxorubicin and pirarubicin (r=0.86-0.98, P＜0.05). CONCLUSION: Sensitivity to chemotherapeutic agents is not associated with the histological type of CCA. Choosing of the appropriate chemotherapeutic regimen for the treatment of CCA requires knowledge of drug sensitivity. MRP3 was correlated with resistance of CCA cell lines to etoposide, doxorubicin and pirarubicin, whereas other chemotherapeutic drugs showed no association. The role of this multidrug resistance-associated protein, MRP3, in chemotherapeutic resistance in CCA patients needs to be further investigated.展开更多
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 hepat...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.展开更多
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 o...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.展开更多
The overzealous and indiscriminate use of most of the synthetic fungicides has created different types of environmental and toxicological problems. Recently, in different parts of the world, attention has been paid to...The overzealous and indiscriminate use of most of the synthetic fungicides has created different types of environmental and toxicological problems. Recently, in different parts of the world, attention has been paid towards exploitation of higher plant products as novel chemotherapeutants in plant protection. The popularity of botanical pesticides is once again increasing and some plant products are being used globally as green pesticides. Pyrethroids and neem products are well established commercially as botanical pesticides and recently some essential oils of higher plants have also been used as antimicrobials against storage pests because of their relatively safe status and wide acceptance by the consumers. Some of the volatile oils, which often contain the principal aromatic and flavouring components of herbs and spices, have been recommended as plant based antimicrobials to retard microbial contamination and reduction in spoilage of food commodities. In the context of agricultural pest management, botanical pesticides are best suited for use in organic food production in industrialized countries but can play a much greater role in the production and post harvest protection of food products in developing countries.展开更多
基金supported by grants from the National Key Technology Research and Development Program of China 2012(BAI06B01)the National Natural Science Foundation of China(81201566)+1 种基金the Specialized Research Fund for the Doctoral Program of Higher Education(20121106110002)Wu Jieping Medical Foundation(LDWMF-SY-2011B002)
文摘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.
基金Supported by TCM Administration Bureau of Shannxi Province,China, No. 199704
文摘AIM： To study the inhibitory effects of Fuzheng Yiliuyin （Decoction for Suppressing Tumors by Strengthening the Body Resistance） in combination with chemotherapeutics on human gastric carcinoma cell strain. METHODS： Fuzheng Yiliuyin （ZY） combined with various kinds of chemotherapeutics was put into two kinds of cultivated human gastric carcinoma cell strains, then its inhibitory effects on human gastric carcinoma cell strains were determind by the MTT method. Flow cytorneter was used to assay the apoptosis rate, and the ultrastructure of gastric carcinoma cells was observed under transmission electron microscope. RESULTS： Obvious apoptosis was seen in gastric carcinoma cells after treatment with ZY for 72 h. ZY and chemical drugs had synergistic inhibition effects on the cultivated gastric carcinoma cells, but the effects were different on various cell strains. The inhibitory effects of ZY could be strengthened by cytotoxic action and apoptosis. ZY combined with tluorouracil, etoposide and cisplatin （EFP） chemotherapeutics had better inhibitory effects on SGC-7901, while ZY combined with EFP or with DDP chemotherapeutics had better inhibitory effects than other drugs on MGC-803. CONCLUSION： ZY induces apoptosis and inhibits the growth of gastric carcinoma cells. ZY has the synergistic function of chemotherapeutics.
基金supported by the National Natural Science Foundation of China(grant no.82073263).
文摘Cancer is characterized by abnormal cell growth and remains a leading global cause of death despite advances in conventional therapies.Limitations such as lack of selectivity,cytotoxic side effects,and multidrug resistance underscore the need for potent anticancer agents.TopoisomeraseⅡ(TOP2)has emerged as a pivotal target for anticancer drugs,categorized as poisons and catalytic inhibitors.While clinically used TOP2-based drugs predominantly act as poisons,concerns regarding their cytotoxicity and DNA-damaging potential persist.In response to these challenges,exploring natural bioactive compounds(NBCs),including small molecules from Chinese herbs,as sources of novel anticancer agents has become a focal point in pharmaceutical research.Recognizing that NBCs alone may not satisfy as anticancer agents,this review aims to comprehensively analyze the current published studies,specifically focusing on the combined applications of TOP2-inhibiting approved chemotherapeutics and natural products.The review explores this approach's potential synergies and challenges,emphasizing the importance of developing effective and targeted anticancer strategies.
基金supported by the National Natural Science Foundation of China(Nos.82225047,82170274,82304665)the National Key Research and Development Program of China(No.2022YFC3501703)+3 种基金Zhejiang Provincial Natural Science Foundation of China(Nos.LZ24H280003,LQ23H280016)the Postdoctoral Fellowship Program of CPSF(No.GZC20233561)the Basic Medical Research Project of Naval Medical University(No.2023QN022)the Key Project at Central Government Level:The Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources(No.2060302).
文摘Paclitaxel(PTX),a valuable natural product derived from Taxus species,exhibits remarkable anti-cancer properties.It penetrates nanopores in microtubule walls,interacting with tubulin on the lumen surface and disrupting microtubule dynamics,thereby inducing cytotoxic effects in cancer cells.PTX and its derivatives have gained approval for treating various diseases due to their low toxicity,high efficiency,and broad-spectrum application.The widespread success and expanding applications of PTX have led to increased demand,raising concerns about accessibility.Consequently,researchers globally have focused on developing alternative production methods and applying nanocarriers in PTX delivery systems to enhance bioavailability.This review examines the challenges and advancements in PTX sourcing,production,physicochemical properties,anti-cancer mechanisms,clinical applications,trials,and chemo-immunotherapy.It aims to provide a comprehensive reference for the rational development and effective utilization of PTX.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82073975,81673563,81102762,82204715,and 82304743).
文摘Chemotherapeutic drugs such as doxorubicin(DOx)and oxaliplatin can induce immunogenic cell death(ICD)in tumor cells.Current studies have demonstrated that peptide-based drugs can also induce ICD in tumor cells.Unlike small molecule drugs,peptide drugs not only enhance the effectiveness of immunotherapy but also offer the advantage of low biotoxicity[1].
基金supported by the National Key R&D Program of China(grant number 2023ZD0502206,2024YFB3213200,Topic No.2024YFB3213204)National Natural Science Foundation of China(nos.82273278,82373514,82373202,82272728,82002630,81772654)+5 种基金the National Key Research and Development Program of China(grant number 2022YFC2404602)Shanghai Hospital Development Center Foundation(grant number SHDC12023108)Scientific and Technological Innovation Action Plan of Shanghai Science and Technology Committee(grant number 22Y31900103)Beijing Science and Technology Innovation Medical Development Foundation(grant number KC2021-JX-0170-9)the Shanghai Association for Science and Technology(nos.201409003000,201409002400,20YF1426200)Shanghai Science and Technology Innovation Action Plan(grant number 23Y41900100).
文摘Osteosarcoma(OS)is the most frequent primary bone sarcomas with high recurrence and poor prognosis.Emerging evidence indicates that membraneless organelles stress granules(SGs),whose assemblies are driven by scaffold protein G3BP1,are extensively involved in tumor,especially in OS.However,how SGs behave and communicate with organelles,particularly nucleoli and mitochondria,during drug challenges remain unknown.This study revealed that chemotherapeutic drugs activated the cysteine protease asparagine endopeptidase(AEP)to specifically cleave the SG core protein G3BP1 at N258/N309 in OS and malignant glioma.tG3BP1-Ns modulated SG dynamics by competitively binding to full-length G3BP1.Strikingly,tG3BP1-Cs,containing a conserved RNA recognition motif CCUBSCUS,sequestered mRNAs of ribosomal proteins and oxidative phosphorylation genes in the nucleoli and mitochondria to repress translation and oxidative stress.Moreover,the inhibition of AEP promoted the tumor-suppressing effect of chemotherapeutic drugs,whereas AEP-cleaved G3BP1 rescue reversed the effect in both OS and glioma models.Cancerous tissues exhibited high levels of AEP and G3BP1 truncations,which were strongly associated with poor prognosis.
文摘Background:Breast cancer still stands to be the foremost contributor to cancer-related incidence and mortality in women globally accounting for about 14%of all female cancer-related deaths worldwide.This research seeks to illustrate the mechanisms and clinical findings of natural products against breast cancer treatment.Methodology:Required data for this review article was retrieved employing several readily obtainable search databases,including Web of Science■(Thomson Reuters,USA),PubMed■(U.S.National Library of Medicine,USA),and SciVerse Scopus■(Elsevier Properties S.A.,USA),taking into consideration certain search terms like“breast cancer,”“natural products against breast cancer,”and“Clinically proven natural products in the treatment of breast cancer”and so on.Results:Several natural products,namely Omega-3 fatty acids,dietary isothiocyanates,curcumin,green tea,flaxseed,limonene,and others,were found to modulate crucial pathways in breast cancer cells.These substances suppressed angiogenesis by downregulating the vascular endothelial growth factor(VEGF),promoted apoptosis by activating caspase enzymes,and prevented cell proliferation by controlling cyclin-dependent kinases.Clinical studies demonstrated improved outcomes in patients receiving these natural products with standard treatment procedures.Discussion:The findings underscore the multifaceted functions of natural products in breast cancer therapy,highlighting their potential to increase the efficacy of conventional treatments while reducing adverse effects.Further exploration of synergistic actions and optimal dosages is needed.Conclusion:Clinically proven natural products represent a potential avenue for breast cancer treatment with their mechanistic insights that facilitate their incorporation into treatment regimens.To maximize clinical applications,future inquiries should center on elucidating the full spectrum of these anticancer functions.
文摘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?
文摘Despite advancements in the areas of omics and chemoinformatics,potent novel biotherapeutic molecules with new modes of actions are needed for leishmaniasis.The socioeconomic burden of leishmaniasis remains alarming in endemic regions.Currently,reports from existing endemic areas such as Nepal,Iran,Brazil,India,Sudan and Afghanistan,as well as newly affected countries such as Peru,Bolivia and Somalia indicate concerns of chemoresistance to the classical antimonial treatment.As a result,effective antileishmanial agents which are safe and affordable are urgently needed.Natural products from both flora and fauna have contributed immensely to chemotherapeutics and serve as vital sources of new chemical agents.This review focuses on a systematic cross-sectional view of all characterized anti-leishmanial compounds from natural sources over the last decade.Furthermore,IC_(50)/EC_(50),cytotoxicity and suggested mechanisms of action of some of these natural products are provided.The natural product classification includes alkaloids,terpenes,terpenoids,and phenolics.The plethora of reported mechanisms involve calcium channel inhibition,immunomodulation and apoptosis.Making avail-able enriched data pertaining to bioactivity and mechanisms of natural products complement current efforts geared towards unraveling potent leishmanicides of therapeutic relevance.
文摘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.
基金Supported by Zhejiang Province Traditional Chinese Medicine Science and Technology Project,No.2024ZL1296.
文摘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.
文摘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.
基金Supported by The Key Scientific and Technological Research Foundation of the National Special Purpose Program,No.2008ZX10002-018
文摘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.
基金supported by the grants from the National Natural Science foundation of China (No. 30772549)the Development Foundation of Medical Science from Public Health Department of Jiangsu Province (No. P200965)
文摘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.
基金Supported by the National Nature Science Foundation of China, No. 39870879Key Technologies R and D Program of China, No. 2002AA2Z3337
文摘AIM: To investigate the combination effect of hTERT antisense oligonucleotide 'Cantide' and three chemotherapeutic drugs (cisplatin, 5-fluorouracil (5-FU) and adriamycin (ADM)) on inhibiting the proliferation of HepG2, BGC and A549 cell lines in vitro, and to investigate the efficacy of Cantide used in combination with cisplatin (DDP) in vivo. METHODS: Cantide was transfected into these tumor cells by Lipofectin, and cell growth activity was calculated by microcytotoxicity assay. In vivo study, cells of HepG2 were implanted in Balb/c nude mice for 4 d. Then Cantide, DDP and Cantide+DDP were given intra peritonea Ily for 24 d respectively. The body weights of the tumor-bearing animals and their tumor mass were measured later to assess the effect of combination therapy in the nude mice. To evaluate the interaction of Cantide and these chemotherapeutic drugs, SAS software and Jin Zhengjun method were used. RESULTS: Combination treatments with 0.1μmol/L Cantide reduced the IC50 of DDP, 5-FU and ADM from 1.07, 4.15 and 0.29 μg/mL to 0.25,1.52 and 0.12 μg/mL respectively. The inhibition ability of DDP, 5-FU and ADM respectively in combination with Cantide in these tumor cells was higher than that of these drugs alone (P<0.0001). And synergism (Q≥1.15)was observed at the lower concentration of DDP (≤1μg/mL) and ADM (≤0.1 μg/mL) with combination of Cantide. In vivo, combination treatment with Cantide and DDP produced the greater growth inhibition of human liver carcinoma cells HepG2 in nude mice (0.65±0.19 g tumor) compared with that when only one of these drugs was used (Cantide group: 1.05±0.16 g tumor, P= 0.0009<0.001; DDP group: 1.13±0.09 g tumor, P= 0.0001<0.001). CONCLUSION: These findings indicate that Cantide may enhance therapeutic effectiveness of chemotherapeutic drugs over a wide range of tumor cells in vitro, and the combination use of Cantide and DDP can produce much higher inhibition rates, as compared with when either of these drugs was used only in vivo.
基金Supported by the Research Grants From the Thailand Research Fund and Khon Kaen University, Thailand Co-first-authors: Nisana Tepsiri and Liengchai Chaturat
文摘AIM: To study the effect of a number of chemotherapeutic drugs on five human intrahepatic cholangiocarcinoma (CCA) cell lines. The expressions of genes that have been proposed to influence the resistance of chemotherapeutic drugs including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), glutathione-S-transferase PI (GSTP1), multidrug resistance protein (MDR1) and multidrug resistance-associated proteins (MRPs) were also determined. METHODS: Five human CCA cell lines (KKU-100, KKU-M055, KKU-M156, KKU-M214 and KKU-OCA17) were treated with various chemotherapeutic drugs and growth inhibition was determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Semi-quantitative levels of gene expression were determined by a reverse transcriptase polymerase chain reaction (RT-PCR). Results of IC_(50) values and the ratios of gene expression were analyzed by linear regression to predict their relationship. RESULTS: Among five CCA cell lines, KKU-M055 was the most sensitive cell line towards all chemotherapeutic drugs investigated, particularly taxane derivatives with IC_(50) values of 0.02-3 nmol/L, whereas KKU-100 was apparently the least sensitive cell line. When compared to other chemotherapeutic agents, doxorubicin and pirarubicin showed the lowest IC_(50) values (＜5 μmol/L) in all five CCA cell lines. Results from RT-PCR showed that TS, MRP1, MRP3 and GSTP1 were highly expressed in these five CCA cell lines while DPD and MRP2 were only moderately expressed. It should be noted that MDR1 expression was detected only in KKU-OCA17 cell lines. A strong correlation was only found between the level of MRP3 expression and the IC_(50) values of etoposide, doxorubicin and pirarubicin (r=0.86-0.98, P＜0.05). CONCLUSION: Sensitivity to chemotherapeutic agents is not associated with the histological type of CCA. Choosing of the appropriate chemotherapeutic regimen for the treatment of CCA requires knowledge of drug sensitivity. MRP3 was correlated with resistance of CCA cell lines to etoposide, doxorubicin and pirarubicin, whereas other chemotherapeutic drugs showed no association. The role of this multidrug resistance-associated protein, MRP3, in chemotherapeutic resistance in CCA patients needs to be further investigated.
文摘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.
文摘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.
文摘The overzealous and indiscriminate use of most of the synthetic fungicides has created different types of environmental and toxicological problems. Recently, in different parts of the world, attention has been paid towards exploitation of higher plant products as novel chemotherapeutants in plant protection. The popularity of botanical pesticides is once again increasing and some plant products are being used globally as green pesticides. Pyrethroids and neem products are well established commercially as botanical pesticides and recently some essential oils of higher plants have also been used as antimicrobials against storage pests because of their relatively safe status and wide acceptance by the consumers. Some of the volatile oils, which often contain the principal aromatic and flavouring components of herbs and spices, have been recommended as plant based antimicrobials to retard microbial contamination and reduction in spoilage of food commodities. In the context of agricultural pest management, botanical pesticides are best suited for use in organic food production in industrialized countries but can play a much greater role in the production and post harvest protection of food products in developing countries.
