This journal publishes the results of investigations into the mode of action and pharmacologic properties of antibacterial, antiviral and antitumor substances. Although experimental work predominates, clinical studies are included. Papers selected for the journal offer data concerning the efficacy, toxicology, and interaction of new drugs in single and combined applications. The journal also publishes studies designed to determine pharmacokinetic properties or evaluate the comparative efficacy of similar preparations. The growth of chemotherapeutic applications is well served through the large number of contributions published in each issue and regular supplement issues devoted to specific themes concerning antibiotic and cytostatic chemotherapy.
Current impact factor: 1.29
Impact Factor Rankings
|2016 Impact Factor||Available summer 2017|
|2014 / 2015 Impact Factor||1.288|
|2013 Impact Factor||1.554|
|2012 Impact Factor||2.066|
|2011 Impact Factor||1.816|
|2010 Impact Factor||2.108|
|2009 Impact Factor||2.028|
|2008 Impact Factor||1.515|
|2007 Impact Factor||1.503|
|2006 Impact Factor||1.511|
|2005 Impact Factor||1.413|
|2004 Impact Factor||1.248|
|2003 Impact Factor||1.184|
|2002 Impact Factor||0.967|
|2001 Impact Factor||1.129|
|2000 Impact Factor||1.021|
|1999 Impact Factor||0.797|
|1998 Impact Factor||0.752|
|1997 Impact Factor||0.709|
|1996 Impact Factor||1.014|
|1995 Impact Factor||0.864|
|1994 Impact Factor||0.842|
|1993 Impact Factor||0.659|
|1992 Impact Factor||0.54|
Impact factor over time
|Document type||Journal / Magazine / Newspaper|
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- Must link to publisher version
Publications in this journal
- [Show abstract] [Hide abstract] ABSTRACT: Background: Cytarabine (Ara-C) is the primary drug in different treatment schemas for acute myeloid leukemia (AML) and requires the human equilibrative nucleoside transporter (hENT1) to enter cells. The deoxycytidine kinase (dCK) enzyme limits its activation rate. Therefore, decreased expression levels of these genes may influence the response rate to this drug. Methods: AML patients without previous treatment were enrolled. The expression of hENT1 and dCK genes was analyzed using RT-PCR. Clinical parameters were registered. All patients received Ara-C + doxorubicin as an induction regimen (7 + 3 schema). Descriptive statistics were used to analyze data. Uni- and multivariate analyses were performed to determine factors that influenced response and survival. Results: Twenty-eight patients were included from January 2011 until December 2012. Median age was 36.5 years. All patients had an adequate performance status (43% with ECOG 1 and 57% with ECOG 2). Cytogenetic risk was considered unfavorable in 54% of the patients. Complete response was achieved in 53.8%. Cox regression analysis showed that a higher hENT1 expression level was the only factor that influenced response and survival. Conclusions: These results highly suggest that the pharmacogenetic analyses of Ara-C influx may be decisive in AML patients.
- [Show abstract] [Hide abstract] ABSTRACT: Background: Mitochondria have emerged as a major target for anticancer therapy because of their critical role in cancer cell survival. Our preliminary works have suggested that dihydroergotamine tartrate (DHE), an antimigraine agent, may have effects on mitochondria. Methods: We examined the effect of DHE on the survival of several lung cancer cells and confirmed that DHE suppressed diverse lung cancer cell growth effectively. To confirm whether such effects of DHE would be associated with mitochondria, A549 cells were employed for the evaluation of several important parameters, such as membrane potential, reactive oxygen species (ROS) generation, apoptosis, ATP production and autophagy. Results: DHE decreased membrane permeability, increased ROS generation as well as apoptosis, and disturbed ATP production. Eventually, mitophagy was activated for damaged mitochondria. Conclusion: Taken together, our findings demonstrate that DHE induces lung cancer cell death by the induction of apoptosis and mitophagy, thus suggesting that DHE can be developed as an anti-lung cancer therapeutic agent.
- [Show abstract] [Hide abstract] ABSTRACT: Background: Adjuvant platinum-based chemotherapy improves survival in women with early-stage epithelial ovarian cancer (EOC). Yet, there is a wide variety in clinical practice. Methods: All patients diagnosed with FIGO I and IIa EOC (2006-2010) in the south of the Netherlands were analyzed. The percentage of patients that received adjuvant chemotherapy was determined as well as the comprehensiveness of staging and outcome. Results: Forty percent (54/135) of the patients with early-stage EOC received adjuvant chemotherapy. Treatment with adjuvant chemotherapy was associated with FIGO stage, clear-cell histology and nonoptimal staging. Optimal staging was achieved in 50%, and nonoptimal staging was associated with advanced age, comorbidity and treatment in a non-referral hospital. Overall, there was no difference in outcome between patients with and without adjuvant chemotherapy. Yet, in grade 3 tumors, adjuvant chemotherapy seems beneficial. Conclusions: Selective treatment of patients with early-stage EOC might reduce adjuvant chemotherapy without compromising outcome.
- [Show abstract] [Hide abstract] ABSTRACT: Background: Metallo-β-lactamases (MBLs) producing strains of Acinetobacter baumannii are serious etiological agents of hospital infections worldwide. Among the β- lactams, carbapenems are the most effective antibiotics used against A. baumannii. However, resistance to these drugs among clinical strains of A. baumannii has been increasing in recent years. In this study, the antimicrobial sensitivity patterns of A. baumannii strains isolated from eleven different hospitals in Tehran, Iran, and the prevalence of MBL genes (bla-VIM and bla-IMP) were determined. Method: During a period of 5 months, 176 isolates of A. baumannii were collected from different clinical specimens from hospitalized patients in Tehran. All isolates were confirmed by biochemical methods. The isolates were tested for antibiotic sensitivity by the Kirby-Bauer disk diffusion method. Following minimum inhibitory concentration determination, imipenem-resistant isolates were further tested for MBL production by the double disk synergy test (DDST) method. PCR assays were performed for the detection of the MBL genes bla-IMP and bla-VIM. Results: The DDST phenotypic method indicated that among the 169 imipenem-resistant isolates, 165 strains were MBL positive. The PCR assays revealed that 63 of the overall isolates (36%) carried the bla-VIM gene and 70 strains (40%) harbored bla-IMP. Conclusions: It is obvious that nosocomial infections associated with multidrug-resistant Acinetobacter spp. are on the rise. Therefore, the determination of antibiotic sensitivity patterns and screening for MBL production among A. baumannii isolates is important for controlling clinical Acinetobacter infections.
- [Show abstract] [Hide abstract] ABSTRACT: Background: We examined whether the weight loss that occurs with platinum-based chemotherapy in lung cancer patients is associated with chemotherapy side effects, treatment completion rates and therapeutic effect. Methods: We retrospectively reviewed charts of advanced lung cancer patients treated with ≥2 cycles of platinum-based chemotherapy. Patients were divided into 2 groups based on ≥5 or <5% weight loss. Relationships between weight loss and other variables were investigated. Results: Among 114 patients, 18 (15.8%) experienced ≥5% weight loss. Significantly more patients with small-cell lung cancer (SCLC) than with non-SCLC were found to have ≥5% weight loss (30.8 vs. 11.4%, p = 0.023). Patients with ≥5% weight loss experienced higher incidences of grade 3-4 leukopenia (p = 0.008) and neutropenia (p = 0.005), and treatment completion rates were lower in this group (p = 0.035). Weight loss was not significantly associated with therapeutic effect. Conclusion: The weight loss in patients with advanced lung cancer receiving platinum-based chemotherapy is associated with SCLC, grade 3-4 leukopenia, neutropenia and a decrease in treatment completion rate.
- [Show abstract] [Hide abstract] ABSTRACT: Background: We investigated the efficacy and safety of biweekly irinotecan and cisplatin (IP) as first-line treatment in advanced gastric cancer patients. Methods: Irinotecan 125 mg/m2 on day 1 and cisplatin 60 mg/m2 on day 2 were administrated every 14 days. UGT1A1*28/*6 and toxicities were analyzed. Results: Forty-one eligible patients were enrolled. Fifteen patients, who were defined as the high-dose group, received starting doses of irinotecan 125 mg/m2. Twenty-six patients, who were defined as the low-dose group, received starting doses of irinotecan 80 mg/m2 and cisplatin 50 mg/m2. The response rate was 53.3% in the irinotecan high-dose group and 53.8% in the irinotecan low-dose group. The most common grade 3/4 toxicity was neutropenia (68.3%). No significant difference in grade 3/4 neutropenia was found between patients with the wild-type genotype and those with variant genotypes for UGT1A1*28 or UGT1A1*6. Conclusions: The combination of biweekly irinotecan 80 mg/m2 and cisplatin 50 mg/m2 was active and tolerable. The role of the UGT1A1 genotype in clinical toxicity of an IP regimen requires further investigation.
- [Show abstract] [Hide abstract] ABSTRACT: Objective: To determine the efficacy of first-generation single-agent epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy in advanced non-small-cell lung cancer patients with known EGFR mutation status, we undertook this pooled analysis. Method: We searched for randomized controlled trials (RCTs) in Medline, Embase, the Cochrane Controlled Trials Register, the Science Citation Index, and the American Society of Clinical Oncology annual meetings. Results: Out of 2,129 retrieved articles, 19 RCTs enrolling 2,016 patients with wild-type EGFR tumors and 1,034 patients with mutant EGFR tumors were identified. For these EGFR mutant patients, single-agent EGFR-TKI therapy improved progression-free survival (PFS) over chemotherapy: the summary hazard ratios (HRs) were 0.41 (p < 0.001) for the first-line setting and 0.46 (p = 0.02) for the second-/third-line setting. For those EGFR wild-type patients, single-agent EGFR-TKI therapy did not do as well as chemotherapy in the first-line setting (HR = 1.65, p = 0.03) and in the second-/third-line setting (HR = 1.27, p = 0.006). No statistically significant difference was observed in terms of overall survival (OS). Using platinum-based doublet chemotherapy as a common comparator, indirect comparison showed the superior efficacy of single-agent EGFR-TKI therapy over EGFR-TKIs added to chemotherapy in PFS [HR = 1.35 (1.03, 1.77), p = 0.03]. Additionally, a marginal trend towards the same direction was found in the OS analysis [HR = 1.16 (0.99, 1.35), p = 0.06]. Interestingly, for those EGFR wild-type tumors, single-agent EGFR-TKI therapy was inferior to EGFR-TKIs added to chemotherapy in PFS [HR = 0.38 (0.33, 0.44), p < 0.001] and OS [HR = 0.83 (0.71, 0.97), p = 0.02]. Conclusions: For these EGFR mutant patients, single-agent EGFR-TKI therapy prolonged PFS over chemotherapy. However, single-agent EGFR-TKI therapy was inferior to chemotherapy in PFS for those EGFR wild-type patients. Single-agent EGFR-TKI therapy could improve PFS over the combination of EGFR-TKIs and chemotherapy in these EGFR mutant patients. However, EGFR-TKIs combined with chemotherapy could provide additive PFS and OS benefit over single-agent EGFR-TKI therapy in those EGFR wild-type patients.
- [Show abstract] [Hide abstract] ABSTRACT: Background: Owing to the need for effective and tolerable new regimens for the treatment of patients with metastatic breast cancer (MBC) previously treated with anthracyclines and/or taxanes, we aimed to assess the activity and safety of the gemcitabine plus capecitabine combination chemotherapy. Methods: Sixty-four patients were enrolled. Treatment consisted of gemcitabine 1,000 mg/m2 intravenously on days 1 and 8, plus oral capecitabine at 1,250 mg/m2 twice daily on days 1-14. The primary end point was the overall response rate (ORR). Secondary objectives included the disease control rate (DCR), overall survival (OS), progression-free survival (PFS), toxicity, and predictive factors. Results: In the 64 patients, the ORR and DCR was 28.1 and 67.2%. Median OS and PFS were 23.6 and 13.4 months, respectively. Toxicities were mild and curable. Conclusion: The combination of gemcitabine and capecitabine is an effective and tolerable treatment for MBC previously treated with anthracyclines and/or taxanes.
- [Show abstract] [Hide abstract] ABSTRACT: Background: Surgical resection is the only curative treatment for extrahepatic bile duct cancer. Additionally, the recurrence rate after curative surgery is relatively high, requiring adjuvant therapy. However, the efficacy of adjuvant chemotherapy compared with surgery alone has not yet been clarified. This study aimed to evaluate the efficacy of adjuvant chemotherapy and identify prognostic factors influencing survival in extrahepatic bile duct cancer patients who underwent curative surgical resection. Methods: Ninety-seven patients with extrahepatic bile duct cancer who underwent curative resection between January 2005 and December 2010 were retrospectively analyzed. Results: Among the 97 patients, 31 underwent adjuvant chemotherapy and 66 did not. The 5-year overall survival rate was 34% for patients who underwent adjuvant chemotherapy. There was no significant difference for overall survival between patients who underwent adjuvant chemotherapy and those who did not (p = 0.228). On multivariate analysis, postoperative carbohydrate antigen 19-9 levels and histologic grade were independent prognostic factors related to long-term survival (p < 0.05). Conclusions: Postoperative adjuvant chemotherapy did not improve survival after surgical resection for extrahepatic bile duct cancer.
- [Show abstract] [Hide abstract] ABSTRACT: This report describes a case of Crimean-Congo hemorrhagic fever with widespread hemorrhages and multiple organ dysfunction syndrome in a 46-year-old patient from an endemic region. Although the patient had numerous poor prognostic factors, he was discharged in a healthy condition after 17 days of hospitalization with close monitoring and supportive care. Tranexamic acid was successfully used together with other supportive treatments.
Article: Antibiotics and Breastfeeding[Show abstract] [Hide abstract] ABSTRACT: During the breastfeeding period, bacterial infections can occur in the nursing mother, requiring the use of antibiotics. A lack of accurate information may lead health care professionals and mothers to suspend breastfeeding, which may be unnecessary. This article provides information on the main antibiotics that are appropriate for clinical use and the interference of these antibiotics with the infant to support medical decisions regarding the discontinuation of breastfeeding. We aim to provide information on the pharmacokinetic factors that interfere with the passage of antibiotics into breast milk and the toxicological implications of absorption by the infant. Publications related to the 20 most frequently employed antibiotics and their transfer into breast milk were evaluated. The results demonstrate that most antibiotics in clinical use are considered suitable during breastfeeding; however, the pharmacokinetic profile of each drug must be observed to ensure the resolution of the maternal infection and the safety of the infant.
- [Show abstract] [Hide abstract] ABSTRACT: Background: Pemetrexed is an antifolate chemotherapeutic agent approved for use in non-small cell lung cancer (NSCLC). The mammalian target of rapamycin (mTOR) pathway is implicated in lung cancer development and inhibited by temsirolimus. Methods: We performed a phase I study evaluating the combination of pemetrexed and temsirolimus in advanced non-squamous NSCLC. Results: Eight patients were enrolled in this study. The dose-limiting toxicities included grade 4 thrombocytopenia, grade 3 leukopenia and grade 3 neutropenia. The maximum tolerated dose was determined to be pemetrexed 375 mg/m2 intravenously on day 1 and temsirolimus 25 mg intravenously on days 1, 8 and 15. No objective responses were noted and 3 patients had stable disease as the best response. Conclusion: The combination of pemetrexed and temsirolimus is feasible and well tolerated. This combination may be further evaluated in patients with mTOR pathway activation, particularly in those with TSC1 or STK11 mutations.
- [Show abstract] [Hide abstract] ABSTRACT: Background: We studied the efficacy and safety of cabazitaxel in unselected real-life patients. Patients and methods: We retrospectively investigated all patients with metastatic prostate cancer (mPC) treated with cabazitaxel 25 mg/m2 i.v. every 3 weeks combined with oral prednisolone (10 mg once daily) after first-line docetaxel chemotherapy. Study issues were to report patient characteristics and cabazitaxel data in terms of tolerance and efficacy. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method. All data were compared with TROPIC results. Results: From 2011 to 2014, 41 patients received cabazitaxel; 15 patients (37%) had a performance status (PS) ≥2 versus 7% (p < 0.0001) in TROPIC, and 38 patients (93%) presented a Gleason score ≥7 at baseline (vs. 60%; p < 0.0001). All patients had metastatic disease at baseline. Previous therapies were radiotherapy in 17 patients (41 vs. 61%; p = 0.01) and surgery in 24 patients (59 vs. 52%; p = 0.4). The median number of cabazitaxel cycles was 5 (1-10) versus 6 (3-10) in TROPIC. Five patients completed 10 cycles of cabazitaxel (12%) versus 28% in TROPIC (p = 0.03). Toxicities were anemia (12 patients, 29%), diarrhea (9 patients, 22%), nausea (7 patients, 17%), pain (6 patients, 15%), sepsis (4 patients, 10%), neutropenia (3 patients, 7%) and urinary tract infection (1 patient, 2%). The tumor response rate was 19.5 versus 14.4% in TROPIC (nonsignificant). PFS was 4.5 months (95% CI 3.3-6.4) in our analysis and 2.8 months (95% CI 2.4-3.0) in TROPIC. OS was 12.1 months (95% CI 9.2 to not reached) and 15.1 months (95% CI 14.1-16.3), respectively. Conclusion: In our unselected mPC patients with poorer baseline clinical conditions and aggressive disease, cabazitaxel seems efficient and not more toxic than in the TROPIC study.
- [Show abstract] [Hide abstract] ABSTRACT: Background: Trabectedin plus pegylated liposomal doxorubicin (PLD) proved efficacious as second-line treatment for patients with recurrent ovarian cancer (ROC). Methods: We report a single-center retrospective analysis of the efficacy and tolerance of trabectedin 1.1 mg/m2 every 3 weeks in a cohort of real-life ROC patients. Results: From February 2012 to January 2014, 17 patients were treated with trabectedin alone or combined with PLD. Median age was 61 years (range: 48-78). Performance status was 0-1 in 16 patients (94%). Disease response rate was 53% and disease control rate was 76%. At the end of the follow-up, 8 patients (47%) were alive. Median overall survival was 17.6 months (95% CI 13.6 to not reached). Median progression-free survival was 6.7 months (95% CI 5.4-10.0). The most frequent grade 3-4 toxicities were neutropenia (n = 4, 24%) and nausea/vomiting (n = 4, 24%). Conclusion: Trabectedin combined with PLD seems efficient in and well tolerated by real-life ROC patients.
- [Show abstract] [Hide abstract] ABSTRACT: Background: We investigated the targeting of microtubules (MT) and F-actin cytoskeleton (AC) of the human pathogenic yeast Cryptococcus neoformans with agents for cancer therapy, in order to examine whether this yeast cytoskeleton could become a new antifungal target for the inhibition of cell division. Methods: Cells treated with 10 cytoskeleton inhibitors in yeast extract peptone dextrose medium were investigated by phase-contrast and fluorescence microscopy, and growth inhibition was estimated by cell counts using a Bürker chamber and measuring absorbance for 6 days. Results: Docetaxel, paclitaxel, vinblastine sulfate salt, cytochalasin D and chlorpropham [isopropyl N-(3-chlorophenyl) carbamate] did not inhibit proliferation. The MT inhibitors methyl benzimidazole-2-ylcarbamate (BCM), nocodazole, thiabendazole (TBZ) and vincristine (VINC) disrupted MT and inhibited mitoses, but anucleated buds emerged on cells that increased in size, vacuolated and seemed to die after 2 days. The response of the cells to the presence of the actin inhibitor latrunculin A (LA) included the disappearance of actin patches, actin cables and actin rings; this arrested budding and cell division. However, in 3-4 days, resistant budding cells appeared in all 5 inhibitors. Disruption of the MT and AC and inhibition of cell division and budding persisted only when the MT and AC inhibitors were combined, i.e. VINC + LA, BCM + LA or TBZ + LA. Conclusion: The MT and AC of C. neoformans are new antifungal targets for the persistent inhibition of cell division by combined F-actin and MT inhibitors.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.