Clinical cancer drugs最新文献

{"title":"A Novel Therapeutic Approach in Acute Promyelocytic Leukemia with All-trans retinoic Acid and Cyclin-dependent Kinase Inhibitors","authors":"G. Tsolkas, D. Komninou, E. Briasoulis, E. Hatzimichael, Papanikolaou Na","doi":"10.2174/2212697X05666180713164713","DOIUrl":"https://doi.org/10.2174/2212697X05666180713164713","url":null,"abstract":"DOI: 10.2174/2212697X05666180713164713 Abstract: Background: Acute promyelocytic leukemia (APL) is characterized by chromosomal translocations, which generate fusion oncogenic proteins. In 95% of cases, in frame fusion of the RARα gene to the PML gene, gives rise to the PML-RARα chimeric gene in patients with t(15;17)q22;q21. In addition, in 99% of cases, APL cells also express the germ cell-specific Cyclin A1 protein, which has been shown to contribute to APL-like disease in mouse models. Re-localization and degradation of PML-RARα with pharmacologic levels of all-trans retinoic acid (ATRA) may cause serious side effects such as the development of myelodysplastic syndrome, cutaneous T-cell lymphoma and skin cancers. Here, we exploit the expression of cyclin A1 and of the fusion protein and show that combined, sub-pharmacologic doses of ATRA and cyclin-dependent kinase inhibitors are more efficacious than either agent alone at inducing etc at inducing APL cell differentiation. Methods: Cultured NB4 APL cells were used to compare the degree of differentiation by ATRA and olomoucine or roscovitine, two cyclin-dependent kinase inhibitors alone or in combination. Differentiation was monitored with the NBT reaction, quantitation of proliferation and monitoring the levels of CDK4, PML-RARα and C/EBP proteins using immunoblots. Results: ATRA or roscovitine alone are effective at inducing inhibition of proliferation and differentiation at pharmacologic levels whereas olomoucine alone is not. In contrast, the combined use of sub-pharmacologic doses of ATRA with either olomoucine or roscovitine is more effective at inhibiting APL cell proliferation than ATRA, olomoucine or roscovitine alone with implications for the treatment of APL. Conclusion: We demonstrate that in NB4 cells, the combination of ATRA/ olomoucine or ATRA/roscovitine leads to more potent differentiation accompanied by a reduction in CDK4 protein levels, decreased degradation of the fusion protein and up-regulation of the transcription factor C/EBPε.","PeriodicalId":91228,"journal":{"name":"Clinical cancer drugs","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/2212697X05666180713164713","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45721994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of TAK-264, an Antibody-Drug Conjugate in Pancreatic Cancer Cell Lines and Patient-Derived Xenograft Models.","authors":"Anna R Schreiber,&nbsp;Anna Nguyen,&nbsp;Stacey M Bagby,&nbsp;John J Arcaroli,&nbsp;Betelehem W Yacob,&nbsp;Kevin Quackenbush,&nbsp;Joe L Guy,&nbsp;Thomas Crowell,&nbsp;Bradley Stringer,&nbsp;Hadi Danaee,&nbsp;Thea Kalebic,&nbsp;Wells A Messersmith,&nbsp;Todd M Pitts","doi":"10.2174/2212697X05666180516120907","DOIUrl":"10.2174/2212697X05666180516120907","url":null,"abstract":"<p><strong>Background: </strong>Antibody-drug conjugates (ADCs) are an emerging technology consisting of an antibody, linker, and toxic agent, which have the potential to offer a targeted therapeutic approach. A novel target recently explored for the treatment of pancreatic cancer is guanylyl cyclase C (GCC). The objective of this study was to determine the anti-tumorigenic activity of TAK-264, an investigational ADC consisting of an antibody targeting GCC linked to a monomethyl auristatin E payload <i>via</i> a peptide linker.</p><p><strong>Methods: </strong>The antiproliferative effects of TAK-264 assessed in a panel of eleven pancreatic cancer cell lines. Additionally, ten unique pancreatic ductal adenocarcinoma cancer patient-derived xenograft models were treated with TAK-264 and the efficacy was determined. Baseline levels of GCC were analyzed on PDX models and cell lines. Immunoblotting was performed to evaluate the effects of TAK-264 on downstream effectors.</p><p><strong>Results: </strong>GCC protein expression was analyzed by immunoblotting in both normal and tumor tissue; marked increase in GCC expression was observed in tumor tissue. The <i>in vitro</i> experiments demonstrated a range of responses to TAK-264. Eight of the ten PDAC PDX models treated with TAK-264 demonstrated a statistically significant tumor growth inhibition. Immunoblotting demonstrated an increase in phosphorylated-HistoneH3 in both responsive and less responsive cell lines and PDAC PDX models treated with TAK-264. There was no correlation between baseline levels of GCC and response in either PDX or cell line models.</p><p><strong>Conclusion: </strong>TAK-264 has shown suppression activity in pancreatic cancer cell lines and in pancreatic PDX models. These findings support further investigation of ADC targeting GCC.</p>","PeriodicalId":91228,"journal":{"name":"Clinical cancer drugs","volume":"5 1","pages":"42-49"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/2212697X05666180516120907","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36855172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arachidonic Acid Induces the Migration of MDA-MB-231 Cells by Activating Raft-associated Leukotriene B4 Receptors.","authors":"Atasi De Chatterjee,&nbsp;Debarshi Roy,&nbsp;Priscilla Guevara,&nbsp;Rituraj Pal,&nbsp;Mahesh Naryan,&nbsp;Sukla Roychowdhury,&nbsp;Siddhartha Das","doi":"10.2174/2212697X05666180418145601","DOIUrl":"10.2174/2212697X05666180418145601","url":null,"abstract":"<p><strong>Background: </strong>The migration of tumor cells is critical in spreading cancers through the lymphatic nodes and circulatory systems. Although arachidonic acid (AA) and its soluble metabolites have been shown to induce the migration of breast and colon cancer cells, the mechanism by which it induces such migration has not been fully understood.</p><p><strong>Objective: </strong>The effect of AA on migratory responses of the MDA-MB-231 cell line (a triple-negative breast cancer cell) was examined and compared with MCF-7 (estrogen-receptor positive) breast cancer cells to elucidate the mechanism of AA-induced migration.</p><p><strong>Methods: </strong>Migrations of breast cancer cells were examined with the help of wound-healing assays. AA-induced eicosanoid synthesis was monitored by RP-HPLC. Cellular localizations of lipoxygenase and lipid rafts were assessed by immunoblot and confocal microscopy.</p><p><strong>Results: </strong>AA treatment stimulated the synthesis of leukotriene B4 (LTB₄) and HETE-8, but lowered the levels of prostaglandin E2 (PGE₂), prostaglandin D2 (PGD₂), and HETE-5 in MDA-MB-231 cells. Further analysis indicated that AA increased the expression of 5-lipoxygenase (5-LOX) in this cell line and inhibiting its expression by small molecule inhibitors lowered the production of LTB₄ and reduced migration. In contrast, MCF-7 cells did not show any appreciable changes in eicosanoid synthesis, 5-LOX expression, or cellular migration.</p><p><strong>Conclusion: </strong>Our results suggest that AA treatment activates the BLT1 receptor (present in membrane microdomains) and stimulates the synthesis of LTB₄ production, which is likely to be associated with the migration of MDA-MB-231 cells.</p>","PeriodicalId":91228,"journal":{"name":"Clinical cancer drugs","volume":"5 1","pages":"28-41"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/2212697X05666180418145601","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36689637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UPFRONT DPD DEFICIENCY DETECTION TO SECURE 5-FU ADMINISTRATION: PART 2- APPLICATION TO HEAD-AND-NECK CANCER PATIENTS.","authors":"Manon Launay,&nbsp;Joseph Ciccolini,&nbsp;Claire Fournel,&nbsp;Carmelo Blanquicett,&nbsp;Charlotte Dupuis,&nbsp;Nicolas Fakhry,&nbsp;Florence Duffaud,&nbsp;Sébastien Salas,&nbsp;Bruno Lacarelle","doi":"10.2174/2212697x04666170817123425","DOIUrl":"https://doi.org/10.2174/2212697x04666170817123425","url":null,"abstract":"<p><strong>Background: </strong>Upfront screening for dihydropyrimidine dehydrogenase (DPD) deficiency in patients scheduled for 5-FU should help reduce the risk of toxicities by preventive adaptive dosing. Our group has developed a simple functional testing categorizing patients upon their DPD status, i.e. extensive metabolizer (EM) or poor metabolizer (PM) patients, using UH2/U ratio measurement in plasma as a surrogate for DPD activity. 5-FU dosing can then be tailored according to DPD deficiency status.</p><p><strong>Objectives: </strong>We present here an observational study of this strategy implemented in routine clinical practice when treating head-and-neck cancer patients.</p><p><strong>Results: </strong>A total of 218 evaluable adult patients were treated with a 5-FU-regimen, with DPD-based adaptive dosing. Among them, 20 (9%) were identified as PM and received subsequently a 20-50% reduced dosing of 5-FU as compared with EM patients (2102 ±254 mg VS. 2577 ±353mg, p<0.001 ttest). Gender (Female) was associated with higher risk for being PM (p=0.01, Pearson's Chi squared test). Overall, early severe toxicities were seen only in 5% of patients, all being EM with standard dosing. Similarly, overall severe toxicities were observed in 12.8% of patients only, both figures being markedly lower than usually reported with standard 5-FU. Despite the average -20% reduction in 5-FU dosing between PM and EM patients, clinical efficacy was not statistically different between the two groups (p = 0.2774, chi-square test).</p><p><strong>Conclusion: </strong>This study shows that 5-FU-related toxicities can be greatly reduced in routine clinical practice by the upfront detection of DPD deficient patients with simple adaptive dosing strategy.</p>","PeriodicalId":91228,"journal":{"name":"Clinical cancer drugs","volume":"4 2","pages":"122-128"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906055/pdf/nihms955089.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36031727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Antibody Therapeutics Targeting Mesothelin In Solid Tumors","authors":"Xiao-yan Zhao, B. Subramanyam, N. Sarapa, S. Golfier, H. Dinter","doi":"10.2174/2212697X03666160218215744","DOIUrl":"https://doi.org/10.2174/2212697X03666160218215744","url":null,"abstract":"Abstract: Background Monoclonal antibodies have become attractive clinical anti-cancer drugs in the last 3 decades due to their targeting specificity and suitable pharmacokinetic properties. Mesothelin is a tumor-associated antigen with limited expression in normal tissues. It is frequently over-expressed on the cell membrane of a number of epithelial malignancies (e.g. mesothelioma, pancreatic, ovarian, lung, triple negative breast and gastric cancers). Methods Mesothelin is validated as a suitable antibody target for cancer therapy. A number of novel antibody therapeutics targeting mesothelin in development are compared and their mechanisms of action are also discussed. Both basic science and clinical data are provided to give a complete veiw of how an agent is developed from bench to bedside. Results Novel antibody therapeutics, including unconjugated monoclonal antibodies, recombinant immunotoxins and antibody-drug conjugates, targeting mesothelin exert anti-tumor activities by different mechanisms of action. Based on the convincing preclinical data generated with these molecules, the antibody therapeutics have been brought into early clinical evaluation where initial promising results were obtained. Conclusion These antibody therapeutics directed against mesothelin are expected to have different safety profiles, based on their different mechanism of action. Further clinical development will reveal which of these molecules shows the best efficacy and widest therapeutic window and thus is best suited to bring benefit to the patients.","PeriodicalId":91228,"journal":{"name":"Clinical cancer drugs","volume":"3 1","pages":"76 - 86"},"PeriodicalIF":0.0,"publicationDate":"2016-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/2212697X03666160218215744","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68181496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transforming Mutations of Jak3 (A573V and M511I) Show Differential Sensitivity to Selective Jak3 Inhibitors.","authors":"G Steven Martinez,&nbsp;Jeremy A Ross,&nbsp;Robert A Kirken","doi":"10.2174/2212697X03666160610085943","DOIUrl":"https://doi.org/10.2174/2212697X03666160610085943","url":null,"abstract":"<p><strong>Background: </strong>A medical need exists for successfully treating patients afflicted with leukemia and especially those that relapse and ultimately become refractory to front line chemotherapies. Leukemia cases are particularly high within Hispanic populations where this disease is among the most frequently occurring cancer. A possible cause is somatic mutations in Janus tyrosine kinase (Jak3). Fourteen somatic mutations have been reported in Jak3, including M511I and A573V, from patients with various forms of leukemia. While several of these Jak3 mutations have been shown to possess transforming ability in cell lines, whether these mutations are susceptible to Jak3 selective inhibitors remains less clear.</p><p><strong>Methods: </strong>The IL-3 dependent pro-B cell line Ba/F3 was virally transduced with plasmids encoding GFP and different mutant forms of Jak3, some of which conferred IL-3 independence. Sensitivity to pre-clinical and clinical Jak3 selective inhibitors was assessed for cellular viability and growth.</p><p><strong>Results: </strong>Two Jak3 mutations conferred IL-3 independent growth in Ba/F3 cells. However, the level of drug sensitivity varied with respect to Jak3 inhibitors NC1153, CP-690,550, and EP-009.</p><p><strong>Conclusion: </strong>Jak3 inhibitors CP-690,550 and NC1153 showed efficacy in reducing viability of Ba/F3 cells transformed with mutant forms of Jak3, thus providing new therapeutic strategies to treat these types of cancer.</p>","PeriodicalId":91228,"journal":{"name":"Clinical cancer drugs","volume":"3 2","pages":"131-137"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/2212697X03666160610085943","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35526540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-selective cytotoxicity of a novel pentadiene analogue on human leukemia/ lymphoma cells.","authors":"Yahaira Santiago-Vázquez, U. Das, Armando Varela-Ramírez, Sarah T Baca, Yoshira M. Ayala-Marín, C. Lema, Swagatika Das, Alaa Baryyan, J. Dimmock, R. Aguilera","doi":"10.2174/2212697X03666160830165250","DOIUrl":"https://doi.org/10.2174/2212697X03666160830165250","url":null,"abstract":"BACKGROUND A novel series of structurally divergent 1,5-diaryl-3-oxo-1,4-pentadiene analogues 1-10 displayed marked cytotoxic potencies towards a number of human leukemia/lymphoma cells. OBJECTIVE To identify novel selective cytotoxic compounds that induce apoptosis. METHODS The Differential Nuclear Staining (DNS) screening protocol was utilized to measure the cytotoxicity of all experimental dienones on several cancerous cells. Additionally, the selective cytotoxicity index was calculated by comparing the dienone's cytotoxicity between leukemia/lymphoma cells vs. non-cancerous cells. Furthermore, to discern whether a selected dienone induced cell death via apoptosis or necrosis on T-lymphocyte leukemia cells, diverse approaches were utilized to detect individual biochemical facets of apoptosis. RESULTS The dienones were tested for their anti-neoplastic efficiency on human leukemia/lymphoma-derived cell lines. Special emphasis was applied on dienone 1, on the basis of its sub-micromolar cytotoxicity (CC50=0.43+0.02 μM) and high selective cytotoxicity index (11.1) exerted on T-leukemia cells. In general, dienone 1 showed the most potent cytotoxic properties as compared to other dienones and a related reference cytotoxin curcumin as well as the EF-24 curcumin analogue. Dienone 1 caused cell death by apoptosis in Jurkat cells as evidenced by inducing phosphatidylserine externalization, mitochondrial depolarization and caspase-3/7. These effects were mainly attributed to the induction of apoptotic pathways. CONCLUSION The novel dienone 1 was found to exhibit potent anti-leukemia activity by inducing programmed cell death/apoptosis. Consequently, dionone 1 should be developed further to examine its potential efficacy to combat malignancies in a pre-clinical animal model.","PeriodicalId":91228,"journal":{"name":"Clinical cancer drugs","volume":"3 2 1","pages":"138-146"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68181641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arsenic-exposed Keratinocytes Exhibit Differential microRNAs Expression Profile; Potential Implication of miR-21, miR-200a and miR-141 in Melanoma Pathway.","authors":"Horacio O Gonzalez, C. Lema, R. Kirken, R. A. Maldonado, Armando Varela-Ramírez, R. Aguilera","doi":"10.2174/2212697X02666150629174704","DOIUrl":"https://doi.org/10.2174/2212697X02666150629174704","url":null,"abstract":"Long-term exposure to arsenic has been linked to cancer in different organs and tissues, including skin. Here, non-malignant human keratinocytes (HaCaT) were exposed to arsenic and its effects on microRNAs (miRNAs; miR) expression were analyzed via miRCURY LNA array analyses. A total of 30 miRNAs were found differentially expressed in arsenic-treated cells, as compared to untreated controls. Among the up-regulated miRNAs, miR-21, miR-200a and miR-141, are well known to be involved in carcinogenesis. Additional findings confirmed that those three miRNAs were indeed up-regulated in arsenic-stimulated keratinocytes as demonstrated by quantitative PCR assay. Furthermore, bioinformatics analysis of both potential cancer-related pathways and targeted genes affected by miR-21, miR-200a and/or miR-141 was performed. Results revealed that miR-21, miR-200a and miR-141 are implicated in skin carcinogenesis related with melanoma development. Conclusively, our results indicate that arsenic-treated keratinocytes exhibited alteration in the miRNAs expression profile and that miR-21, miR-200a and miR-141 could be promising early biomarkers of the epithelial phenotype of cancer cells and they could be potential novel targets for melanoma therapeutic interventions.","PeriodicalId":91228,"journal":{"name":"Clinical cancer drugs","volume":"97 6 1","pages":"138-147"},"PeriodicalIF":0.0,"publicationDate":"2015-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68181459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Role and Targeting of Carcinoembryonic Antigen-related Cell Adhesion Molecule 6 (CEACAM6) in Human Malignancies.","authors":"Benny Johnson, Daruka Mahadevan","doi":"10.2174/2212697X02666150602215823","DOIUrl":"10.2174/2212697X02666150602215823","url":null,"abstract":"<p><strong>Background: </strong>Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is a member of the CEA family of cell adhesion proteins that belong to the immunoglobulin superfamily. CEACAM6 is normally expressed on the surface of myeloid (CD66c) and epithelial surfaces. Stiochiomertic expression of members of the CEA family (CEACAM1, 5, 6, 7) on epithelia maintains normal tissue architecture through homo-and hetero-philic interactions. Dysregulated over-expression of CEACAM6 is oncogenic, is associated with anoikis resistance and an invasive phenotype mediated by excessive TGFβ, AKT, FAK and SRC signaling in human malignancies.</p><p><strong>Methods: </strong>Extensive literature review through PubMed was conducted to identify relevant preclinical and clinical research publications regarding CEACAM6 over the last decade and was summarized in this manuscript.</p><p><strong>Results: </strong>CEACAM5 and 6 are over-expressed in nearly 70% of epithelial malignancies including colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDA), hepatobiliary, gastric, breast, non-small cell lung and head/neck cancers. Importantly, CEACAM6 is a poor prognostic marker in CRC, while its expression correlates with tumor stage, metastasis and post-operative survival in PDA. CEACAM6 appears to be an immune checkpoint suppressor in hematologic malignancies including acute lymphoblastic leukemia and multiple myeloma. Several therapeutic monoclonal antibodies or antibody fragments targeting CEACAM6 have been designed and developed as a targeted therapy for human malignancies. A Llama antibody targeting CEACAM6 is being evaluated in early phase clinical trials.</p><p><strong>Conclusion: </strong>This review focuses on the role of CEACAM6 in the pathogenesis and signaling of the malignant phenotype in solid and hematologic malignancies and highlights its potential as a therapeutic target for anti-cancer therapy.</p>","PeriodicalId":91228,"journal":{"name":"Clinical cancer drugs","volume":"2 2","pages":"100-111"},"PeriodicalIF":0.0,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cd/ab/CCD-2-100.PMC4997943.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34417932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Importance of Lamivudine Therapy in Liver Cirrhosis Patients Related HBV with Advanced Hepatocellular Carcinoma Receiving Hepatic Arterial Infusion Chemotherapy.","authors":"Koichi Momiyama,&nbsp;Hidenari Nagai,&nbsp;Yu Ogino,&nbsp;Takanori Mukouzu,&nbsp;Daigo Matsui,&nbsp;Michio Kogame,&nbsp;Teppei Matsui,&nbsp;Noritaka Wakui,&nbsp;Mie Shinohara,&nbsp;Yoshinori Igarashi,&nbsp;Yasukiyo Sumino","doi":"10.2174/2212697X02666150602220735","DOIUrl":"https://doi.org/10.2174/2212697X02666150602220735","url":null,"abstract":"<p><strong>Purpose: </strong>We have previously reported that continuous hepatic arterial infusion chemotherapy (HAIC) might be more effective for advanced hepatocellular carcinoma (aHCC) in patients with liver cirrhosis (LC) related to HCV infection (C-LC) or alcohol abuse (A-LC) than in patients who had LC related to HBV infection (B-LC). The aim of the present study was to retrospectively assess the efficacy of lamivudine therapy for B-LC patients with aHCC undergoing HAIC.</p><p><strong>Methods: </strong>Seventeen adult Japanese B-LC patients with aHCC were treated by HAIC with or without lamivudine (100 mg/day) between 2002 and 2008 at our hospital. Their tumors were inoperable according to computed tomography findings. HAIC (LV at 12 mg/hr, CDDP at 10 mg/hr, and 5-FU at 250 mg/22 hr) was given via the proper hepatic artery every 5 days for 4 weeks using a catheter connected to a subcutaneously implanted drug delivery system.</p><p><strong>Results: </strong>Nine of the 17 patients received lamivudine at a dose of 100 mg/day together with HAIC (LAM group), while 8 patients did not receive lamivudine and only had HAIC (non-LAM group). The response rate was 12.5 in the non-LAM group and 0.0% in the LAM group. However, the survival of the LAM group was better than that of the non-LAM group, although there was no significant difference between them. The median survival time of the LAM and non-LAM groups was 310 and 157 days, respectively. HBV-DNA levels were significantly lower after chemotherapy compared with that before chemotherapy in the LAM group. In the non-LAM group, the percentage of Th2 cells before HAIC and after HAIC was significantly higher than in the control group. However, the percentage of Th2 cells in the LAM group after HAIC was not different from that in the control group, although it was significantly higher in the LAM group than in the control group before chemotherapy.</p><p><strong>Conclusions: </strong>These results indicate that lamivudine therapy may prolong the survival of B-LC patients receiving HAIC for aHCC by reducing HBV-DNA level and inhibiting the increase of Th2 cells in host immunity.</p>","PeriodicalId":91228,"journal":{"name":"Clinical cancer drugs","volume":"2 2","pages":"112-118"},"PeriodicalIF":0.0,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/2212697X02666150602220735","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34417933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}