Deciphering resistancemechanisms and novel strategies to overcome drug resistance in ovarian cancer:a comprehensive review

Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy.Drug resistance(DR)poses the most significant challenge in treating patients with existing drugs.The Food and Drug Administration(FDA)has recently approved three new therapeutic drugs,including two poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib and niraparib)and one vascular endothelial growth factor(VEGF)inhibitor(bevacizumab)for maintenance therapy.However,resistance to these new drugs has emerged.Therefore,understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management.In this review,we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.

Drug resistance mechanisms in cancers:Execution of prosurvival strategies

One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions.

Research progress in tumor angiogenesis and drug resistance in breast cancer

Angiogenesis is considered a hallmark pathophysiological process in tumor development. Aberrant vasculature resulting from tumor angiogenesis plays a critical role in the development of resistance to breast cancer treatments, via exacerbation of tumor hypoxia, decreased effective drug concentrations within tumors, and immune-related mechanisms. Antiangiogenic therapy can counteract these breast cancer resistance factors by promoting tumor vascular normalization. The combination of antiangiogenic therapy with chemotherapy, targeted therapy, or immunotherapy has emerged as a promising approach for overcoming drug resistance in breast cancer. This review examines the mechanisms associated with angiogenesis and the interactions among tumor angiogenesis, the hypoxic tumor microenvironment, drug distribution, and immune mechanisms in breast cancer. Furthermore, this review provides a comprehensive summary of specific antiangiogenic drugs, and relevant studies assessing the reversal of drug resistance in breast cancer. The potential mechanisms underlying these interventions are discussed, and prospects for the clinical application of antiangiogenic therapy to overcome breast cancer treatment resistance are highlighted.

Role of targeting ferroptosis as a component of combination therapy in combating drug resistance in colorectal cancer

Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.

Antimicrobial drug resistance of Staphylococcus aureus in dairy products

Objective:To evaluate the prevalence of multidrug resistant Staphylococcus aureus(S.aureus) in dairy products.Methods:Isolation and identification of S.aureus were performed in 3 dairybased food products.The isolates were tested for their susceptibility to 5 different common antimicrobial drugs.Results:Of 50 samples examined,5(10%) were contaminated with 5. aureus.Subsequently,the 5 isolates were subjected to antimicrobial resistance pattern using five antibiotic discs(methicillin,vancomycin,kanamycin,chloramphenicol and tetracycline).Sample 29 showed resistance to methicillin and vancomycin.Sample 18 showed intermediate response to tetracycline.The other samples were susceptible to all the antibiotics tested.Conclusions:The results provide preliminary data on sources of food contamination which may act as vehicles for the transmission of antimicrobial-resistant Staphylococcus.Therefore,it enables us to develop preventive strategies to avoid the emergence of new strains of resistant S.aureus.

In-vitro antimicrobial activity of marine actinobacteria against multidrug resistance Staphylococcus aureus

Objective:To investigate the antibacterial aclivily of marine actinobacteria against multidrug resistance Staphylococcus aureus(MDRSA).Methods:Fifty one actinobacterial strains were isolated from salt pans soil,costal area in Kothapattanam,Ongole,Andhra Pradesh.Primary screening was done using cross-streak method against MDRSA.The bioaclive compounds are extracted from efficient actinobacteria using solvent extraction.The antimicrobial activity of crude and solvent extracts was perfomied using Kirby-Bauer method.MIC for ethyl acetate extract was determined by modified agar well diffusion method.The potent actinobacteria are identified using Nonomura key,Shirling and Gottlieb 1966 with Bergey's manual of determinative bacteriology.Results:Among the fifty one isolates screened for antibacterial activity,SRB25were found efficient against MDRSA.The ethyl acetate extracts showed high inhibition against test organism.MIC test was performed with the ethyl acetate extract against MDRSA and found to be 1 000μg/mL.The isolaled actinobacteria are identified as Streptomyces sp with the help of Nonomura key.Conclusions:The current investigation reveals that the marine actinobacteria from salt pan environment can be able to produce new drug molecules against drug resistant microorganisms.

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

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

Inferring Mycobacterium Tuberculosis Drug Resistance and Transmission using Whole-genome Sequencing in a High TB-burden Setting in China

Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking.Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns.Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023–1.954;P=0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains.Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.

PHLDA2 reshapes the immune microenvironment and induces drug resistance in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable prognosis.The dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment failure.The elucidation of PHLDA2’s involvement in HCC is imperative,and the clinical value of PHLDA2 is also underestimated.Here,bioinformatics analysis was performed in multiple cohorts to explore the phenotype and mechanism through which PHLDA2 may affect the progression of HCC.Then,the expression and function of PHLDA2 were examined via the qRT-PCR,Western Blot,and MTT assays.Our findings indicate a substantial upregulation of PHLDA2 in HCC,correlated with a poorer prognosis.The methylation levels of PHLDA2 were found to be lower in HCC tissues compared to normal liver tissues.Besides,noteworthy associations were observed between PHLDA2 expression and immune infiltration in HCC.In addition,PHLDA2 upregulation is closely associated with stemness features and immunotherapy or chemotherapy resistance in HCC.In vitro experiments showed that sorafenib or cisplatin significantly up-regulated PHLDA2 mRNA levels,and PHLDA2 knockdown markedly decreased the sensitivity of HCC cells to chemotherapy drugs.Meanwhile,we found that TGF-βinduced the expression of PHLDA2 in vitro.The GSEA and in vitro experiment indicated that PHLDA2 may promote the HCC progression via activating the AKT signaling pathway.Our study revealed the novel role of PHLDA2 as an independent prognostic factor,which plays an essential role in TME remodeling and treatment resistance in HCC.

The superiority of PMFs on reversing drug resistance of colon cancer and the effect on aerobic glycolysis-ROS-autophagy signaling axis

Background:Polymethoxylatedflavones(PMFs)are compounds present in citrus peels and other Rutaceae plants,which exhibit diverse biological activities,including robust antitumor and antioxidant effects.However,the mechanism of PMFs in reversing drug resistance to colon cancer remains unknown.In the present study,we aimed to investigate the potential connection between the aerobic glycolysis-ROS-autophagy signaling axis and the reversal of PTX resistance in colon cancer by PMFs.Methods:MTT Cell viability assay and colony formation assay were used to investigate the effect of PMFs combined with PTX in reversing HCT8/T cell resistance ex vivo;the mRNA and protein levels of the target were detected by SDS-PAGE(sodium dodecyl sulfate-polyacrylamide gel electrophoresis),quantitative real-timefluorescence polymerase chain reaction(qRT-PCR)and Western blot protein immunoblotting(WB);An HCT8/T cell xenograft model was established to investigate the MDR reversal activity of PMFs in vivo;The extracellular acidification rate(ECAR)and the oxygen consumption rate(OCR)were detected to assess the cellular oxygen consumption rate and glycolytic process.Results:HCT8/T cells demonstrated significant resistance to PTX,up-regulating the expression levels of ABCB1 mRNA,P-gp,LC3-I,and LC3-II protein,and increasing intracellular reactive oxygen species(ROS)content.PMFs mainly contain two active ingredients,nobiletin,and tangeretin,which were able to reverse drug resistance in HCT8/T cells in a concentration-dependent manner.PMFs exhibited high tolerance in the HCT8/T nude mouse model while increasing the sensitivity of PTX-resistant cells and suppressing tumor growth significantly.PMFs combined with PTX reduced extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)in HCT8/T cells.Additionally,PMFs reduced intracellular ROS content,down-regulated the expression levels of autophagy-related proteins LC3-I,LC3-II,Beclin1,and ATG7,and significantly reduced the number of autophagosomes in HCT8/T cells.Conclusions:The present study demonstrated that PMFs could potentially reverse PTX resistance in colon cancer by regulating the aerobic glycolysis-ROS-autophagy signaling axis,which indicated that PMFs would be potential potentiators for future chemotherapeutic agents in colon cancer.

Antimicrobial Drug Resistance Pattern of <i>Escherichia coli</i>Isolated from Chickens Farms with Colibacillosis Infection

Colibacillosis refers to any localized or systemic infection caused entirely or partly by avian pathogenic Escherichia coli (APEC). Colibacillosis in mammals is most often a primary enteric or urinary tract disease, whereas colibacillosis in poultry is typically a localized or systemic disease occurring secondarily when host defenses have been impaired or overwhelmed by virulent E. coli strains. The purpose of this study was to investigate the antimicrobial drug resistance pattern of Escherichia coli isolated from broiler chickens farms with colibacillosis infection. Dead birds from commercial broiler chicken farms showing signs of colibacillosis were necropsied and swab samples were collected from internal organs and blood aseptically for the isolation of Escherichia coli. Pure colonies of the bacteria were isolated on solid media and the isolates were identified as E. coli based on morphological and biochemical characteristics. For determination of susceptibility to antibacterial agents, the disc diffusion method on Muller-Hinton agar was used. The following antimicrobial agents were tested: gentamycin, oxytetracyline, colistin, ciprofloxacin, doxycycline, nalidixic acid, co-trimoxazole (trimethoprim-sulfamethoxazole), norefloxacin, lincospectin and cefuroxime. The drug resistance patterns of the organisms were determined as a percentage and reported at three levels: susceptible, intermediate and resistant. All the isolates of Escherichia coli showed resistance to several antibiotics and a pattern of multiple drug resistance was observed. The highest rate of resistance was observed against nalidixic acid (100%) and the least rate of resistance was observed against gentamycin (17%). According to the results of this research care must be taken to avoid secondary infection (colibacillosis) in chicken farms and also avoid in careless antimicrobial consumption in food animals including chickens.

Betaine combined with traditional Chinese medicine ointment to treat skin wounds in microbially infected diabetic mice

BACKGROUND Skin wounds are highly common in diabetic patients,and with increasing types of pathogenic bacteria and antibiotic resistance,wounds and infections in diabetic patients are difficult to treat and heal.AIM To explore the effects of betaine ointment(BO)in promoting the healing of skin wounds and reducing the inflammation and apoptosis of skin cells in microbially infected diabetic mice.METHODS By detecting the minimum inhibitory concentrations(MICs)of betaine and plant monomer components such as psoralen,we prepared BO with betaine as the main ingredient,blended it with traditional Chinese medicines such as gromwell root and psoralen,and evaluated its antibacterial effects and safety in vitro and in vivo.The skin infection wound models of ordinary mice and diabetic mice were constructed,and the OTC drugs mupirocin ointment and Zicao ointment were used as controls to evaluate the antibacterial effects in vivo and the anti-inflammatory and anti-apoptotic effects of BO.RESULTS The MICs of betaine against microorganisms such as Staphylococcus aureus(S.aureus),Candida albicans and Cryptococcus neoformans ranged from 4 to 32μg/mL.Gromwell root and psoralea,both of which contain antimicrobial components,mixed to prepare BO with MICs ranging from 16 to 64μg/mL,which is 32-256 times lower than those of Zicao ointment,although the MIC is greater than that of betaine.After 15 days of treatment with BO for USA300-infected ordinary mice,the wound scab removal rates were 83.3%,while those of mupirocin ointment and Zicao ointment were 66.7%and 0%,respectively,and the differences were statistically significant.In diabetic mice,the wound scab removal rate of BO and mupirolacin ointment was 80.0%,but BO reduced wound inflammation and the apoptosis of skin cells and facilitated wound healing.CONCLUSION The ointment prepared by mixing betaine and traditional Chinese medicine can effectively inhibit common skin microorganisms and has a strong effect on the skin wounds of sensitive or drug-resistant S.aureus-infected ordinary mice and diabetic mice.

Molecular characterization of antimicrobial multi-drug resistance in non-typhoidal Salmonellae from chicken and clam in Mangalore, India

Salmonella enterica has been documented as one of the leading causes of salmonellosis throughout the world and is most commonly associated with the consumption of contaminated food products. Thus, this research was aimed at studying the antimicrobial susceptibility pattern and detection of quinolone resistance in Salmonella spp isolated from food of animal origin. Thirty-six Salmonella isolates comprising 8 from poultry and 28 from seafood（clams） were identified, serotyped and characterized for their antimicrobial susceptibility against 10 different antibiotics. Plasmid DNA was isolated from all the isolates by alkaline lysis, quinolone resistant non-typhoidal S. Weltevreden were examined for mutation in the DNA gyrase coding gene. Among the 36 Salmonella isolates, 20 were S. weltevreden（8 from poultry and 12 from seafood） and 16 were S. Typhimurium（from seafood）. All the isolates showed multiple resistance to nalidixic acid, tetracycline, co-trimoxazole and nitrofurantoin, but, interestingly, the isolates were 100% susceptible to ampicillin, chloramphenicol and gentamicin. Resistant isolates from the study carried the genes responsible for resistance to respective antibiotics. The strain S130 isolated in the study showed single point mutation,Asp87Gly, at position 87 in quinolone resistance determining region. It revealed mutation in quinolone resistance determining region as a cause for quinolone resistance in non-typhoidal Salmonellae. The occurrence of genes accountable for plasmid mediated resistance to quinolones（viz., qnrA, qnrB and qnrS） in plasmid of non-typhoidal Salmonellae isolates provides evidence for plasmid mediated quinolone resistance.

Drug sensitivity and drug resistance profiles of human intrahepatic cholangiocarcinoma cell lines

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.

The Prevalence of HIV Drug Resistance among Treatment-failure Individuals and Treatment-nave Individuals in China:A Meta-analysis

Objective To understand drug resistance prevalence among treatment-failure and treatment-nave HIV-positive individuals in China.Methods We searched five electronic databases（Wanfang,CNKI,CQVIP,SinoMed,and Pubmed） for studies of HIV drug resistance.Random-effects models were carried out to estimate the prevalence of drug resistance among treatment-failure and treatment-nave individuals,respectively.Results The estimated nationwide rates of HIV drug resistance to any-class drugs among treatment-failure and treatment-nave individuals were 57%（95% CI：49%-65%） and 3.23%（95% CI：2.47%-4.07%）,respectively.Among the drug classes,the prevalence of resistance to PIs was low（1.45%;95% CI：0.73%-2.33%） in treatment-failure individuals,although high rates of resistance to NNRTIs（54%;95% CI：45%-63%） and NRTIs（40%;95% CI：32%-49%） were found.Resistance to any-class drugs,NNRTIs and NRTIs manifested regional differences,but resistance to PIs did not.Positive correlations were observed between resistance to NNRTIs and NRTIs among treatment-failure and treatment-nave individuals,respectively.Conclusion The prevalence of HIV drug resistance to NNRTIs and NRTIs among treatment-failure individuals was high.In contrast,the prevalence of drug resistance among treatment-nave individuals was low.The epidemics of drug resistance matched current treatment strategies and interventions in China.Surveillance for HIV drug resistance is necessary to assess the sustainability and durability of current treatment regimens.

Distribution and drug resistance of pathogenic bacteria isolated from cancer hospital in 2013

Objective： To understand distribution and drug resistance of pathogenic bacteria from a specialized cancer hospital in 2013 in order to provide a basis for rational clinical antimicrobial agents. Methods： Pathogenic bacteria identification and drug sensitivity tests were performed with a VITEK 2 compact automatic identification system and data were analyzed using WHONET5.6 software.Results： Of the 1,378 strains tested, 980 were Gram-negative bacilli, accounting for 71.1%, in which Klebsiella pneumonia, Escherichia coli and Pseudomonas aeruginosa were the dominant strains. We found 328 Gram-positive coccus, accounting for 23.8%, in which the amount of Staphylococcus aureus was the highest. We identified 46 fungi, accounting for 4.1%. According to the departmental distribution within the hospital, the surgical departments isolated the major strains, accounting for 49.7%. According to disease types, lung cancer, intestinal cancer and esophagus cancer were the top three, accounting for 20.9%, 17.3% and 14.2%, respectively. No strains were resistant to imipenem, ertapenem or vancomycin.Conclusions： Pathogenic bacteria isolated from the specialized cancer hospital have different resistance rates compared to commonly used antimicrobial agents; therefore antimicrobial agents to reduce the morbidity and mortality of infections should be used.

Relationship between Methylation Status of Multi-drug Resistance Protein(MRP) and Multi-drug Resistance in Lung Cancer Cell Lines

Objective： To study the relationship between the methylation status of multi-drug resistance protein （MRP） gene and the expression of its mRNA and protein in lung cancer cell lines. Methods： Human embryo lung cell line WI-38, lung adenocarcinoma cell line SPCA-1 and its drug-resistant cells induced by different concentrations of doxorubicin were treated with restriction endonuclease Eco47III. The methylation status of MRP was examined by PCR, and the expressions of its mRNA and protein were evaluated by in situ hybridization and immunohistochemistry. Results： MRP gene promoter region of WI-38 cells was in hypermethylation status, but the promoter region of MRP in SPCA-1 cells and their resistant derivatives induced by different concentrations of doxorubicin were in hypomethylation status. There were significant differences in the expression of MRP mRNA among WI-38 cell line, SPCA-1 cells and their drug-resistant derivatives induced by different concentration of doxorubicin. Consistently, MRP immunostaining presented similar significant differences. Conclusion： The promoter region of MRP in SPCA-1 lung adenocarcinoma cells was in hypomethylation status. The hypomethylation status of 5＇ regulatory region of MRP promoter is an important structural basis that can increase the activity of transcription and results in the development of drug resistance in lung cancer.

Isolation and Drug Resistance Analysis of Swine Salmonella

In this study, 68 fresh pork samples were collected from several major wholesale markets in Dalian City of Liaoning Province to isolate Salmonella using SS agar medium as selective medium. Salmonella isolates were identified with colony morphology observation and PCR method. The resistance of Salmonella iso- lates to 15 antibiotics was analyzed by broth microdilution susceptibility test. Accord- ing to the result, 12 Salmonella strains were isolated from 68 fresh pork samples, indicating a detection rate of 17.64%; 83.33% of Salmonella strains isolated from fresh pork samples could at least resist one antibiotic; Salmonella strains exhibited the strongest resistance to florfenicol （75.0%）, sarafloxacin hydrochloride （66.7%）, neomycin sulfate （66.7%） and doxycycline hydrochloride （66.7%）, followed by oxyte- tracycline （58.3%）, gentamicin sulphate （58.3%） and mequindox （58.3%）; Salmonella strains exhibited relatively low resistance to ciprofloxacin lactate （50.0%）, en- rofloxacin （50.0%）, ciprofloxacin hydrochloride （50.0%）, amoxicillin （16.7%） and col- istin sulphate （16.7%）. Salmonella in fresh pork samples from wholesale markets in Dalian Economic ＆ Technological Development Zone exhibited a high detection rate, and the isolated Salmonella strains showed extremely high resistance to various an- tibiotics. The strong drug-resistance of Salmonella can also be transmitted through the food chain from the food to the people, which should attract sufficient attention.

Study on Drug Resistance and Relative Mechanisms of Chlamydia Trachomatis

Chlamydia Trachomatis (C.T.) is one of the most common pathogens of human sexually transmitted diseases. Treatment of C.T. infection primarily depends on Tetracyclines, Macrolides and Quinolones, but with the wide use of antibiotics an increasing number of drug-resistant Chlamydia trachomatis cases have been reported. This review summarizes the resistant conditions and the possible resistance mechanisms of C.T..

Liposome-mediated Functional Expression of Multiple Drug Resistance Gene in Human Bone Marrow CD34^+ Cells

Summary: The expression and functional activity of multiple drug resistance (MDR1) gene in human normal bone marrow CD34+ cells was observed. Human normal bone marrow CD34+ cells were enriched with magnetic cell sorting (MACS) system, and then liposome-mediated MDR1 gene was transferred into bone marrow CD34+ cells. Fluorescence-activated cell sorter was used to evaluate the expression and functional activity of P-glycoprotein (P-gp) encoded by MDR1 gene. It was found that the purity of bone marrow CD34+ cells was approximately (91±4.56) % and recovery rate was (72.3±2.36) % by MACS. The expression of P-gp in the transfected CD34+cells was obviously higher than that in non-transfected CD34+ cells. The amount of P-gp in non-transfected CD34+ cells was (11.2±2.2) %, but increased to (23.6±2.34) % 48 h after gene transfection (P<0.0l). The amount of P-gp was gradually decreased to the basic level one week later. The accumulation and extrusion assays showed that the overexpression of P-gp could efflux Rh-123 out of cells and there was low fluorescence within the transfected cells. The functional activity of P-gp could be inhibited by 10 μg/ml verapamil. It was suggested that the transient and highly effective expression and functional activity of P-gp could be obtained by liposome-mediated MRD1 transferring into human normal bone marrow CD34+ cells.