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Biomedical subjects

Masashi Kobayashi

Publications and source records attributed to Masashi Kobayashi.

At least 19 recordsLinked to original sources
PubMed2025

Stratifying Lung Adenocarcinoma Risk with Multi-ancestry Polygenic Risk Scores in East Asian Never-Smokers.

BACKGROUND: Lung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction. METHODS: PRSs were developed using genome-wide association study summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. Single-ancestry models included PRS-25, PRS-CT, and LDpred2; multi-ancestry models included LDpred2+PRS-EUR128, PRS-CSx, and CT-SLEB. Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium (FLCCA) and externally validated in the Nanjing Lung Cancer Cohort (NJLCC). We assessed predictive accuracy via AUC, with 10-year and (age 30-80) absolute risks estimates. RESULTS: The best multi-ancestry PRS, using East Asian and European data via CT-SLEB (clumping and thresholding, super learning, empirical Bayes), outperformed the best East Asian-only PRS (LDpred2; AUC=0.629, 95% CI:0.618,0.641), achieving an AUC of 0.640 (95% CI:0.629,0.653) and odds ratio of 1.71 (95% CI:1.61,1.82) per SD increase. NJLCC Validation confirmed robust performance (AUC =0.649, 95% CI: 0.623, 0.676). The top 20% PRS group had a 3.92-fold higher LUAD risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41, nine years earlier. CONCLUSIONS: Multi-ancestry PRS approaches enhance LUAD risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

East Asian never smokers↗
PubMed2007

GFP chimeric models exhibited a biphasic pattern of mesenchymal cell invasion in tendon healing.

The healing of an injured musculoskeletal system requires an influx of mesenchymal cells that can differentiate into osteoblasts, fibroblasts, chondroblasts, and skeletal myoblasts. However, whether these mesenchymal cells arise from the circulation (bone marrow) or the injured tissues themselves has been controversial. To reveal the spatiotemporal characteristics of the reparative mesenchymal cells, we investigated the healing process after patellar tendon injury using two types of green fluorescent protein (GFP) chimeric rats; one expressing GFP in the circulating cells, and the other expressing it in the patellar tendon. We analyzed the behavior of GFP-positive cells after experimental tendon injury in both chimeric rats to clarify the origin of reparative cells. At 24 h after the injury, the wound contained circulation-derived cells but not tendon-derived cells. Tendon-derived cells first appeared in the wounded area at 3 days after the injury, and had significantly increased in number with time and had maintained a high level of proliferative activity until 7 days after the injury, whereas the circulation-derived cells had decreased in number and had been replaced by the tendon-derived cells. These findings suggest that circulation-derived and tendon-derived cells contribute to the healing of tendons in different periods as part of a biphasic process.

Animals↗
PubMed2006

Isoproterenol suppresses cytokine-induced RANTES secretion in human lung epithelial cells through the inhibition of c-jun N-terminal kinase pathway.

It has been reported that beta2-agonists may potentially exert some anti-inflammatory action in addition to bronchodilation that may contribute to their beneficial effects on asthma control. Bronchial epithelial cells are well known to respond to a range of stimuli by producing various biologically active mediators that can influence airway inflammation. RANTES (regulated on activation, normal T cells expressed and secreted) plays an important role in the pathophysiology of airway inflammation of asthmatics through its chemotactic activity for eosinophils. In this study, the authors investigated whether cytokine-induced RANTES release from BEAS-2B human bronchial epithelial cells could be modulated by beta-agonist isoproterenol (ISO). The possible involvement of c-jun N-terminal kinase (JNK) pathway was also studied. Combination of tumor necrosis factor-alpha and interleukin-1beta (cytokine mix) increased RANTES release from BEAS-2B cells and stimulated JNK activity. Similar to JNK inhibitor SP600125, ISO inhibited not only the production of RANTES but also the activation of JNK pathway in cytokine mix-stimulated BEAS-2B cells. The effect of ISO was mediated by the beta2-adrenoceptor, since it was blocked by ICI 118,551, a selective beta2-receptor antagonist, but not by atenolol, a selective beta1-receptor antagonist. Adenylyl cyclase activator forskolin reproduced the effects of ISO. Isoproterenol was found to inhibit the release of RANTES from the human bronchial epithelial cells, at least in part, through the inhibition of JNK signaling pathway.

Cell Line↗
PubMed2006

Ionizing radiation suppresses FAP-1 mRNA level in A549 cells via p53 activation.

Ionizing radiation (IR) is known to upregulate cell surface Fas through p53 activation in various cells. However, the signaling pathway intermediating between p53 activation and cell surface Fas upregulation remains to be elucidated. Recently, Fas-associated phosphatase-1 (FAP-1) has been reported to associate with Fas and inhibit cell surface Fas expression. We evaluated the expression of FAP-1 mRNA following IR in A549 cells. Ionizing radiation inhibited the expression of FAP-1 mRNA. Pretreatment with p53 inhibitor pifithrin alpha cancelled the IR-induced downregulation of FAP-1 mRNA. These results suggest that IR-induced p53 activation may upregulate cell surface Fas via the down-modulation of FAP-1.

Benzothiazoles↗
PubMed2006

Outcome of one-year of specialist care of patients with type 2 diabetes: a multi-center prospective survey (JDDM 2).

OBJECTIVE: Specialist care is reportedly associated with favorable therapeutic results, although detailed outcomes of recent large-scale prospective surveys of specialist care have yet to be published. The goal of this study was to elucidate the effects of one year's specialist care on the management of type 2 diabetes. PATIENTS AND METHODS: A multi-centered, prospective observational study was undertaken. 754 type 2 diabetes patients, who made their first visit to one of eleven participating outpatient clinics specializing in diabetes care, were enrolled. Routine structured diabetes care according to established guideline, including diabetes self-management education, was provided to all patients at each clinic visit. Parameters relating to glycemic control, serum lipids, blood pressure, patient follow-up status and others were followed for twelve months. RESULTS: The HbA(1C) level had improved significantly from 8.4+/-2.2% at baseline to 6.8+/-1.2% after six months and was 7.0+/-1.3% after twelve months (mean+/-SD). The higher the baseline HbA(1C) level, the greater the subsequent improvement. Moreover, the most dramatic improvements in HbA(1C) levels were seen within the first three months. The proportion of patients satisfying all of the therapeutic goals was extremely low at baseline and remained at less than 10% after twelve months of specialist care. CONCLUSIONS: Diabetic patients under specialist care experienced substantial improvement, especially in glycemic control, as early as a few months after the first visit. However, 35 percent of patients dropped out during the 12-month study period and this is one area that needs to be improved.

Aged↗
PubMed2006

The status of diabetes control and antidiabetic drug therapy in Japan--a cross-sectional survey of 17,000 patients with diabetes mellitus (JDDM 1).

The number of diabetic patients has been increasing in Japan and consequently diabetic complications are the most important target to be prevented through improving glycemic control. In order to describe the glycemic control status and treatment of diabetic patients by specialists in Japan over three years, from 2000 to 2002, we examined HbA1c, other laboratory data and the modality of drug therapy in the study population, 8170 in 2000, 11,831 in 2001, and 16,934 in 2002. Patients were registered at clinics and hospitals that were members of the Japan Diabetes Clinical Data Management Study Group (JDDM). HbA1c levels, other laboratory data, and details of drug therapy were collected and analyzed using SPSS and MS Access. The mean HbA1c levels were essentially unchanged during the study periods, ranging from 7.9% to 7.8%, and from 7.1% to 7.0%, in type 1 and type 2 diabetic patients, respectively. In type 2 diabetes, the frequency of oral hypoglycemic agents (OHA) use increased from 44.9% to 51.4%, while the use of diet-only therapy decreased from 29.9% to 25.4% over the study period. Although the systolic blood pressure was slightly above target, the mean blood pressure and the mean lipid profile were mostly within the treatment goals set by the Japan Diabetes Society. This first report from a large scale study of the daily management of diabetes in Japan revealed that the average HbA1c level was superior to most of the results reported from other countries. Nonetheless, 66% of the patients still had HbA1c levels and half of the patients had other laboratory parameters including blood pressure and lipid profile that were greater than those recommended by the Japan Diabetes Society. The nature of diabetes drug therapy in Japan has gradually changed as new drugs have appeared in the market.

Aged↗
PubMed2006

Actual usage and clinical effectiveness of insulin preparations in patients with Type 1 diabetes mellitus in Japan: CoDiC-based analysis of clinical data obtained at multiple institutions (JDDM 3).

To clarify the actual usage of insulin preparations and their effectiveness on glycaemic control in patients with Type 1 diabetes mellitus in Japan, we analyzed clinical data collected via CoDiC, an electronic system for diabetes data collection and management, at 28 institutes. Of 18,470 diabetic patients registered with CoDiC in June, 2003, 12,279 patients were being treated with insulin preparations and/or oral hypoglycemic agents, with 861 of these patients having Type 1 diabetes mellitus and 11,418 patients having Type 2 diabetes. Three analytical surveys were carried out with the Type 1 diabetes patients. Study I: Cross-sectional survey on the treatment in 2002. Six hundred and thirteen patients received intensive conventional insulin treatment (ICT). The number of patients receiving rapid-acting insulin analogue (RA) was greater than that of patients receiving regular insulin (R). Serum CPR was lower in the patients with ICT than in the patients with conventional insulin treatment (CT). Study II: Survey on the changes in the actual usage and clinical effectiveness of insulin preparations, based on the data input in 2001 and 2002. The number of patients with ICT using RA insulin markedly increased. Study III: Analysis of the participants' clinical course over the 18-month period of the study from the time of first consultation. The dose of insulin increased during the term. The average HbA1c level fell drastically and reached to 7.5% over the first 9 months of the study and then remained between a range of 7.5% and 8% for the rest of the study period. In conclusion, ICT is actively performed and the RA insulin analogues are widely used in Type 1 diabetic patients in Japan. Basal-bolus therapy should be used to treat Type 1 diabetic patients with postprandial serum CPR of less than 0.5 ng/ml. It is difficult to obtain the ideal glycaemic control in Type 1 diabetic patients with the currently available insulin preparations.

Adult↗
PubMed2006

Three cases of the nodular pulmonary amyloidosis with a longterm observation.

Longterm observation with chest radiograph and computed tomography (CT) scan was performed for pulmonary amyloidosis. There are few reports of primary pulmonary amyloidosis with a longterm observation. We encountered three cases of nodular pulmonary amyloidosis observed by intermittent chest radiograph or CT for 5 years or more. The patients were a 54-year-old man, and 67- and 68-year old women. For diagnosis, transbronchial biopsy and percutaneous lung biopsy were performed. Amyloid nodules grew slowly and two cases showed findings of cavity and calcification.

Aged↗
PubMed2006

Enzymatic and biochemical properties of a novel human serine dehydratase isoform.

A cDNA clone similar to human serine dehydratase (SDH) is deposited in the GenBank/EMBL databases, but its structural and functional bases remain unknown. Despite the occurrence of mRNA, the expected protein level was found to be low in cultured cells. To learn about physicochemical properties of the protein, we expressed the cDNA in Escherichia coli, and compared the expressed protein with that of a hepatic SDH. The purified protein showed l-serine and l-threonine dehydratase activity, demonstrating to be an isoform of SDH. However, their Km and Vmax constants were different in a range of two-order. Removal of Pro128 from the hepatic SDH consisting of 328 residues, which is missing in the corresponding position of the isoform consisting of 329 residues, significantly changed the Michaelis constants and Kd value for pyridoxal 5'-phosphate, whereas addition of a proline residue to the isoform was without effect. These findings suggest the difference in the structures of the active sites of the two enzymes. Another striking feature was that the expressed level of the isoform in E. coli was 7-fold lower than that of the hepatic SDH. Substitution of Val for Leu287 in the isoform dramatically increased the protein level. The high yield of the mutated isoform was also confirmed by the in vitro transcription and translation experiment. The poor expression of the isoform could be explained by the more stable secondary structure of the mRNA than that of the hepatic SDH mRNA. The present findings may provide a clue as to why the protein level in cultured cells is low.

Amino Acid Sequence↗
PubMed2006

Ectopic activity of fibroblast growth factor receptor 1 in hepatocytes accelerates hepatocarcinogenesis by driving proliferation and vascular endothelial growth factor-induced angiogenesis.

Fibroblast growth factor (FGF) signaling mediates cell-to-cell communication in development and organ homeostasis in adults. Of the four FGF receptor (FGFR) tyrosine kinases, only FGFR4 is expressed in mature hepatocytes. Although FGFR1 is expressed by hepatic cell progenitors and adult nonparenchymal cells, ectopic expression is commonly observed in hepatoma cells. Here, we determined whether ectopic FGFR1 is a cause or consequence of hepatocellular carcinoma by targeting a constitutively active human FGFR1 to mouse hepatocytes. Livers of transgenic mice exhibited accelerated regeneration after partial hepatectomy but no signs of neoplastic or preneoplastic abnormalities for up to 18 months. However, in diethylnitrosamine-treated mice, the chronic FGFR1 activity promoted an incidence of 44% adenomas at 4 months and 38% hepatocellular carcinoma at 8 months. No adenoma or hepatocellular carcinoma was observed in diethylnitrosamine-treated wild-type (WT) livers at 4 or 8 months, respectively. At 10 and 12 months, tumor-bearing livers in transgenic mice were twice the size of those in WT animals. Isolated hepatoma cells from the transgenic tumors exhibited a growth advantage in culture. Advanced hepatocellular carcinoma in the transgenic livers exhibited a reduced rate of necrosis. This was accompanied by a mean microvessel density of 2.7 times that of WT tumors and a markedly higher level of vascular endothelial growth factor. In cooperation with an initiator, the persistent activity of ectopic FGFR1 in hepatocytes is a strong promoter of hepatocellular carcinoma by driving cell proliferation at early stages and promoting neoangiogenesis at late stages of progression.

Animals↗
PubMed2006

Easier node dissection after chemoradiotherapy for lung cancer with collagen insertion at mediastinoscopy.

OBJECTIVE: Induction chemoradiotherapy followed by anatomical resection is a current therapeutic strategy for non-small-cell lung cancer with mediastinal node involvement. Dense peritracheal fibrosis and sclerosis after chemoradiotherapy cause difficult mediastinal node dissection. We evaluated a novel technique to make the mediastinal node dissection easier after induction therapy. METHODS: At the end of mediastinoscopic node biopsy for staging of lung cancer, cotton-type collagen was inserted anterior and lateral to the trachea in patients with pathologically confirmed mediastinal node involvement (n=45). The induction therapy consisted of concurrent use of platinum-based chemotherapy and hyperfractionated radiotherapy. After the chemoradiotherapy all patients underwent a pulmonary resection with complete mediastinal node dissection 7-12 weeks after the collagen insertion. Surgical findings of the mediastinum and the time for node dissection were compared with those without collagen insertion at mediastinoscopy after chemoradiotherapy (n=5). RESULTS: All five patients without collagen insertion showed sclerotic and fibrotic change of mediastinal nodes with severe adhesion to the trachea. In 42 of 45 patients with collagen insertion (93.3%) the collagen remained unabsorbed and separated the mediastinal nodes from the trachea. Mediastinal node dissection was easily accomplished by removing mediastinal tissues lateral and anterior to the collagen. The rate of mediastinal node separation was significantly higher with collagen insertion than without (p<0.0001). The times for node dissection in patients with and without collagen insertion showed no significant difference. CONCLUSION: Cotton-type collagen insertion at staging mediastinoscopy for lung cancer separates the mediastinal nodes from the trachea and makes the node dissection easier after induction chemoradiotherapy.

Adult↗
PubMed2006

Phase I study of weekly cisplatin, vinorelbine, and concurrent thoracic radiation therapy in patients with locally advanced non-small-cell lung cancer.

BACKGROUND: The combination of chemotherapy and thoracic radiation therapy (TRT) is considered as a standard treatment for locally advanced non-small-cell lung cancer (NSCLC). Although the frequent interaction of anticancer agents and irradiation may produce stronger radio-sensitizing effects, the daily administration of these agents is complicated. We therefore used weekly administration of these agents, and conducted a phase I study of weekly cisplatin, vinorelbine, and concurrent TRT. The purpose of this study was to identify the maximum tolerated dose (MTD), the dose-limiting toxicity (DLT), and the recommended dose of this treatment. METHODS: Patients with locally advanced NSCLC were enrolled in this study. Both cisplatin and vinorelbine were given intravenously on a weekly schedule for 6 weeks, starting on the first day of TRT, i.e., on days 1, 8, 15, 22, 29, and 36. The total dose of TRT was 60 Gy. The dose of cisplatin was fixed at 20 mg/m(2) per week. The starting dose of vinorelbine was 15 mg/m(2) per week (dose level 1). RESULTS: Nine patients were enrolled in this study. All three patients at dose level 1 experienced DLTs. We decreased the dose of vinorelbine to 10 mg/m(2) per week (dose level 0). Two of the six patients at dose level 0 experienced DLTs. Therefore, dose level 1 was considered as the MTD, and dose level 0 as the recommended dose. The DLTs of this treatment were esophagitis, fatigue, infection, and hyponatremia. CONCLUSION: The recommended dose of cisplatin is 20 mg/m(2) per week and that of vinorelbine is 10 mg/m(2) per week with standard TRT. A phase II study of this treatment is warranted.

Aged↗
PubMed2006

Angled forceps used for transbronchial biopsy in which standard forceps are difficult to manipulate: a comparative study.

OBJECTIVES: To evaluate the usefulness of the Sasada transbronchial angled forceps (STAF) in patients with peripheral pulmonary lesions (PPLs), which are difficult to manipulate with standard forceps. METHODS: We have invented the STAF, a forceps with an angled tip. One hundred ten patients with PPLs that were difficult to reach with standard forceps were retrospectively evaluated. The patients first underwent bronchoscopy with a standard forceps and then with the STAF. The specimens obtained with standard forceps and those obtained with STAF were separately fixed and analyzed histologically. We compared the histologic diagnosis of the specimens obtained by STAF with that obtained by the specimens obtained with standard forceps. Statistical significance was calculated with the McNemar chi(2) statistic. RESULTS: The diagnostic yield of all lesions from the specimens obtained with STAF (86 of 110 lesions; 78.2%) was significantly higher than that of lesions from the specimens obtained with standard forceps (43 of 110 lesions; 39.1%; p < 0.001). Among malignant lesions, the yield obtained with STAF (60 of 72 lesions; 83.3%) was significantly higher than that obtained with standard forceps (32 of 72 lesions; 44.4%; p < 0.001). Among benign lesions, the yield obtained with STAF (26 of 38 lesions; 68.4%) was also significantly higher than that obtained with standard forceps (11 of 38 lesions; 28.9%; p < 0.001). Among the different lesion areas, the right upper lobe plus the left upper division gave the greatest difference in yield (STAF, 46 of 60 lesions; 76.7%; standard forceps, 22 of 60 lesions; 36.7%; p < 0.001). Among the different size ranges, the diagnostic yields obtained with STAF were significantly higher than that obtained with standard forceps except for the size range of < or = 10 mm. There were two complications, pneumothorax and bronchial bleeding, both of which were controlled easily. CONCLUSIONS: The STAF was shown to be useful for obtaining specimens that were sufficient for histologic diagnosis from PPLs that were difficult to manipulate with standard forceps.

Adenocarcinoma↗
PubMed2005

Adiponectin inhibits endothelial synthesis of interleukin-8.

Adiponectin is an antiatherogenic adipokine that inhibits inflammation by mechanisms that are not completely understood. We explored the effect of adiponectin on endothelial synthesis of interleukin-8 (IL-8), a pro-inflammatory chemokine that plays a role in atherogenesis. Adiponectin decreased the secretion of IL-8 from human aortic endothelial cells (HAEC) stimulated with tumor necrosis factor-alpha (TNF-alpha). Adiponectin also inhibited IL-8 mRNA expression induced by TNF-alpha. Phosphorylation of IkappaB-alpha was decreased by adiponectin, but phosphorylation of ERK, SAPK/JNK, and p38MAPK were unaffected. Adiponectin increased intra-cellular cAMP levels in HAEC in a dose-dependent manner; PKA activity was also increased. The inhibitory effect of adiponectin on TNF-alpha-induced IL-8 synthesis was inhibited by pretreatment with Rp-cAMP, a PKA inhibitor. These observations suggest that adiponectin inhibits IL-8 synthesis through inhibition of a PKA dependent NF-kappaB signaling pathway. We also showed that adiponectin enhances Akt phosphorylation. The inhibitory effect of adiponectin on TNF-alpha-induced IL-8 synthesis was abrogated in part by pretreatment with the PI3 kinase inhibitor LY294002 or by Akt siRNA transfection, suggesting that Akt activation might inhibit IL-8 synthesis induced by TNF-alpha. We conclude that inhibition of NF-kappaB and activation of Akt phosphorylation may mediate adiponectin inhibition of atherosclerosis.

Adenylate Kinase↗
PubMed2005

Altered subcellular distribution of estrogen receptor alpha is implicated in estradiol-induced dual regulation of insulin signaling in 3T3-L1 adipocytes.

We investigated the mechanisms by which estrogen alters insulin signaling in 3T3-L1 adipocytes. Treatment with 17beta-estradiol (E2) did not affect insulin-induced tyrosine phosphorylation of insulin receptor. E2 enhanced insulin-induced tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), IRS-1/p85 association, phosphorylation of Akt, and 2-deoxyglucose uptake at 10(-8) m, but inhibited these effects at 10(-5) m. A concentration of 10(-5) m E2 enhanced insulin-induced phosphorylation of IRS-1 at Ser(307), which was abolished by treatment with a c-Jun NH(2)-terminal kinase inhibitor. In addition, the effect of E2 was abrogated by pretreatment with a specific estrogen receptor antagonist, ICI182,780. Membrane-impermeable E2, E2-BSA, did not affect the insulin-induced phosphorylation of Akt at 10(-8) m, but inhibited it at 10(-5) m. Furthermore, E2 decreased the amount of estrogen receptor alpha at the plasma membrane at 10(-8) m, but increased it at 10(-5) m. In contrast, the subcellular distribution of estrogen receptor beta was not altered by the treatment. These results indicate that E2 affects the metabolic action of insulin in a concentration-specific manner, that high concentrations of E2 inhibit insulin signaling by modulating phosphorylation of IRS-1 at Ser(307) via a c-Jun NH(2)-terminal kinase-dependent pathway, and that the subcellular redistribution of estrogen receptor alpha in response to E2 may explain the dual effect of E2.

3T3 Cells↗
PubMed2005

Doxorubicin induces expression of multidrug resistance-associated protein 1 in human small cell lung cancer cell lines by the c-jun N-terminal kinase pathway.

Multidrug resistance (MDR) is a major impediment to successful chemotherapy for lung cancer. Overexpression of multidrug resistance-associated protein 1 (MRP1) appears to be involved in MDR development in lung cancer cells. A number of chemotherapeutic agents including doxorubicin (DOX) were reported to induce MRP1 expression in human lung cancer cells. In our study, we investigated the mechanism by which DOX induces MRP1 expression in human small cell lung cancer (SCLC) cell lines, GLC4 and NCI-H82. These cells expressed MRP1 protein at low levels and were sensitive to DOX. Doxorubicin at 50 nM induced a marked increase in MRP1 expression in 24 hr, and stimulated c-jun N-terminal kinase (JNK) activity. Treatment with a JNK inhibitor, SP600125, significantly inhibited MRP1 induction. Furthermore, transfection with JNK1 and JNK2 antisense oligonucleotides markedly inhibited DOX-induced MRP1 expression. Chromatin immunoprecipitation assays revealed an enhanced recruitment of phosphorylated c-jun to the MRP1 promoter containing the AP-1 site upon DOX stimulation, which was inhibited by pretreatment with SP600125. Surprisingly, GLC4 cells exposed to DOX for 24 hr maintained increased MRP1 expression and resistance to DOX for at least 3 weeks. Pretreatment with SP600125 before DOX stimulation blocked the appearance of the MDR phenotype as well as MRP1 induction in GLC4 cells. These findings suggest that JNK activation may play an essential role for the induction of MRP1 protein in human SCLC cells by chemotherapeutic agents and that combined treatment of a JNK inhibitor with anticancer drugs may prevent the development of MDR by the abrogation of MRP1 induction.

Antibiotics, Antineoplastic↗