Journal of Cancer Research and Clinical Oncology (J Canc Res Clin Oncol)

Publisher: Deutsche Krebsgesellschaft, Springer Verlag

Journal description

Official Organ of the Deutsche Krebsgesellschaft The Journal of Cancer Research and Clinical Oncology contains significant and up-to-date articles within the fields of experimental and clinical oncology. The Journal which is chiefly devoted to Original papers and Rapid communications (given priority treatment by the Editors) also includes Reviews as well as Editorials and Guest editorials on current controversial topics. The section Letters to the editors provides a forum for a rapid exchange of comments and information concerning previously published papers and topics of current interest. Meeting reports provide current information on the latest results presented at important congresses. The following fields are covered: Carcinogenesis - etiology mechanisms · Molecular biology · Recent developments in tumor therapy · General diagnosis · Laboratory diagnosis · Diagnostic and experimental pathology · Oncologic surgery · Epidemiology.

Current impact factor: 3.08

Impact Factor Rankings

2015 Impact Factor Available summer 2016
2014 Impact Factor 3.081
2013 Impact Factor 3.009
2012 Impact Factor 2.914
2011 Impact Factor 2.558
2010 Impact Factor 2.485
2009 Impact Factor 2.261
2008 Impact Factor 2.217
2007 Impact Factor 2.366
2006 Impact Factor 2.469
2005 Impact Factor 2.503
2004 Impact Factor 2.409
2003 Impact Factor 2.162
2002 Impact Factor 2.197
2001 Impact Factor 2.194
2000 Impact Factor 1.789
1999 Impact Factor 1.052
1998 Impact Factor 1.183
1997 Impact Factor 1.154
1996 Impact Factor 1.093
1995 Impact Factor 1.459
1994 Impact Factor 1.654
1993 Impact Factor 1.307
1992 Impact Factor 1.82

Impact factor over time

Impact factor

Additional details

5-year impact 2.94
Cited half-life 5.30
Immediacy index 0.65
Eigenfactor 0.01
Article influence 0.72
Website Journal of Cancer Research and Clinical Oncology website
Other titles Journal of cancer research and clinical oncology (Online), J cancer res clin oncol
ISSN 1432-1335
OCLC 43039749
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Springer Verlag

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    • Author's post-print on any open access repository after 12 months after publication
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    • Must link to publisher version
    • Set phrase to accompany link to published version (see policy)
    • Articles in some journals can be made Open Access on payment of additional charge
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: Several prognostic indices (PI) have been developed to stratify patients with brain metastases in groups with good or bad prognosis. The aim of our study was to compare nine prognostic scores for patients with brain metastases (BM) of breast cancer receiving radiotherapy. Methods: The clinical data of 139 breast cancer patients with BM were collected retrospectively. All patients were treated with cerebral radiotherapy or surgery followed by radiotherapy between January 2007 and December 2012. The prognostic value and accuracy of recursive partitioning analysis (RPA), RPA II, graded prognostic assessment (GPA), basic score for BM, Breast-RPA, Breast-GPA, Rades Score 2011, Germany Score and Breast Rades Score were assessed. Results: The median survival after BM diagnosis in our cohort was 14 months. The overall 6-month, 1-, 2- and 3-year survival rates were 49.6, 37.4, 20.9 and 13.7 %, respectively. Most of the PI were associated with OS, but univariate analysis favored GPA regarding OS. GPA was the most accurate score to identify patients with long (longer than 12 months) and Breast-GPA patients with short (<3 months) life expectancy. Conclusions: GPA and Breast-GPA seem to be the most useful scores and perform better than other PI for breast cancer patients with BM receiving radiotherapy.
    Journal of Cancer Research and Clinical Oncology 10/2015; DOI:10.1007/s00432-015-2049-4
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    ABSTRACT: Introduction: Hematopoietic stem cell transplantation (HCT) is considered a standard treatment for high-risk acute myeloid leukemia (AML) in first or second complete remission (CR). Unfortunately, not all patients achieve complete remission prior to HCT. We sought to establish predictive factors for survival after HCT for refractory AML after FLAMSA-RIC. Patients and methods: We analyzed the outcome of 44 consecutive patients aged between 21 and 65 years transplanted at the University Hospitals of Jena and Leipzig for refractory AML between 2006 and January 2013. Conditioning for HCT was performed with chemotherapy consisting of fludarabine, cytarabine, and amsacrine followed by total body irradiation or busulfan combined with cyclophosphamide. Antithymocyte globulin was given when transplanting from unrelated donors (FLAMSA-RIC). Results: Estimated overall survival (OS) and event-free survival (EFS) at 3 years after a median follow-up of 34 (range 6-71) months were 15 and 12 %, respectively. Causes of death were relapse in 66 %, infection in 11 %, and graft-versus-host disease (GvHD) in 7 % of all patients. Twenty-five from 42 evaluable patients (60 %) achieved CR 4 weeks after HCT, while eight patients had partial remission (PR), and nine patients had stable disease (SD). Another six patients with PR and SD achieved CR (overall CR rate 74 %) from 4 weeks to day 90 after HCT following reduction in immunosuppression. The strongest favorable factors in univariate analysis for OS, EFS, and RI were ≥98 % total donor chimerism 2-4 weeks after HCT and <3 lines of pretreatment prior to HCT. In addition, better OS was detected in patients with <20 % bone marrow blasts alone (32 vs. 5 % at 3 years) and in combination with <3 lines of pretreatment (38 vs. 4 % at 3 years). Only a trend for better EFS and lower RI was observed in patients with limited chronic GvHD. In addition, a lower RI was seen in patients with <5 % blasts 4 weeks after HCT. Multivariate analysis revealed that ≥98 % donor chimerism 2-4 weeks after HCT for OS, EFS, and RI and <3 lines of pretreatment for OS and EFS are the strongest predictors for better outcome. Conclusion: FLAMSA-RIC shows long-term survival in refractory AML patients. Factors for favorable outcome are <20 % bone marrow blasts prior to HCT, <3 lines of pretreatment and complete donor chimerism after HCT.
    Journal of Cancer Research and Clinical Oncology 10/2015; DOI:10.1007/s00432-015-2050-y
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    ABSTRACT: Introduction: Treatment of patients (pts) with acute myelogenous leukaemia (AML) above 60 years remains a challenge. We report long-term follow-up of the AML97 study, where pts were registered at diagnosis and received treatment dependent on their comorbidities: dose-intense cytarabine (AraC) and anthracycline in the curative arm, and low-dose chemotherapy in the palliative arm or best supportive care. Materials and methods: A total of 618 pts were enrolled in this protocol (curative 471, palliative 115 and supportive 32). In the curative arm, complete remission (CR) was obtained in 66.8 % of pts and the estimated probability of being alive at 2 years was 0.30 (±0.02 SE). In multivariate analysis, gender (p = 0.005), performance status (p = 0.04) and cytogenetics (p = 0.002) were significant factors for CR. With a median follow-up of 10 (range 0.1-11.8) years, the estimated probability of being event-free after 2 and 5 years according to cytogenetics was 0.48 ± 0.11 and 0.48 ± 0.11 for favourable, 0.20 ± 0.03 and 0.09 ± 0.03 for normal, 0.18 ± 0.06 and 0.10 ± 0.05 for other standard risk and 0.10 ± 0.03 and 0.05 ± 0.02 for unfavourable karyotypes, respectively. The median survival time for pts treated with palliative chemotherapy was 54 and 11 days with best supportive care only. Conclusion: In conclusion, treatment of older AML pts with dose-intense AraC is feasible in the majority of pts and induces high rates of CR. Nevertheless, except for favourable karyotype, OS and event-free survival remain low. These results need to be viewed in relation to the new modalities including stem cell transplantation following non-myeloablative conditioning, epigenetic and molecular therapies.
    Journal of Cancer Research and Clinical Oncology 09/2015; DOI:10.1007/s00432-015-2045-8
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    ABSTRACT: Purpose: The endoplasmic reticulum (ER) stress response is a therapeutic target for pharmacologic intervention in cancer cells. We hypothesized that combining carfilzomib (CFZ), a proteasome inhibitor, and vorinostat (SAHA), a histone deacetylase (HDAC) inhibitor, would synergistically activate ER stress in non-small cell lung cancer (NSCLC) cell lines, resulting in enhanced anti-tumor activity. Methods: Five NSCLC cell lines were treated with CFZ, SAHA, or the combination and cell proliferation measured using the MTT assay. Calcusyn software was utilized to determine the combination index as a measure of synergy. Cell viability and cytotoxicity were measured using trypan blue exclusion, CellTiter, and CytoTox assays. Western blot was used to measure markers of apoptosis, ER stress, and oxidative stress-related proteins. Reactive oxygen species (ROS) was measured using the fluorophore CM-H2DCFDA. Results: Synergistic activity was observed for all cell lines following 48 and 72 h of combined treatment. H520 and A549 cell lines were used to assess viability and apoptosis. In both cell lines, increased death and cleaved caspase-3 were observed following combination treatment as compared with single-agent treatments. Combination therapy was associated with upregulation of ER stress-regulated proteins including activating transcription factor 4, GRP78/BiP, and C/EBP homologous protein. Both cell lines also showed increased ROS and the oxidative stress-related protein, heat shock protein 70. Conclusion: Combining proteasome inhibition with HDAC inhibition enhances ER stress, which may contribute to the synergistic anticancer activity observed in NSCLC cell lines. Further preclinical and clinical studies of CFZ + SAHA in NSCLC are warranted.
    Journal of Cancer Research and Clinical Oncology 09/2015; DOI:10.1007/s00432-015-2047-6
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    ABSTRACT: Purpose: As one form of tumor invasion, cancer cells can invade the extracellular matrix (ECM) through tracks that have been physically remodeled by cancer-associated fibroblasts (CAFs). However, CAFs are a heterogeneous population with diverse matrix-remodeling capacities. The purpose of this study was to investigate how CAFs with various matrix-remodeling capacities influence cancer cell invasion. Methods: We established single-cell-derived clones from three primary cultures of CAFs from lung adenocarcinoma patients (Case 1, 5 clones; Case 2, 5 clones; and Case 3, 7 clones). Using a co-culture model, we evaluated the correlations between the number of invaded cancer cells and the remodeling areas generated by CAF clones in each case. Results: When A549 lung adenocarcinoma cells and CAF clones were co-cultured, both the numbers of invaded cancer cells and the remodeling areas generated by the CAF clones varied greatly. The number of invaded cancer cells was moderately and strongly correlated with the remodeling areas generated by each CAF clone originating from Cases 1 and 2 (R (2) value = 0.53 and 0.68, respectively), suggesting that the remodeling areas in the ECM may determine the number of invaded cancer cells. In contrast, the number of invaded cancer cells was not correlated with the remodeling areas generated by CAF clones originating from Case 3, suggesting that factors other than the remodeling areas might determine the number of invading cancer cells. Conclusions: These findings showed two types of fibroblast-dependent cancer cell invasion that are dependent on and independent of the remodeling areas generated by CAFs.
    Journal of Cancer Research and Clinical Oncology 09/2015; DOI:10.1007/s00432-015-2046-7
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    ABSTRACT: Purpose: Norepinephrine (NE) has been implicated in epithelial-mesenchymal transition (EMT) of cancer cells. However, the underlying mechanism is poorly understood. The goal of this study was to explore the effect of NE on cancer cell EMT and to investigate the potential mechanism. Methods: HT-29 and A549 cells were treated with NE, β-adrenergic receptor (β-AR) antagonist (propranolol) or inhibitor of transforming growth factor-β (TGF-β) receptor type I kinase (Ly2157299). Morphology of cells was observed with optical and electron microscope and immunofluorescence staining. Cellular migration and invasion were tested with transwell migration assay and Matrigel invasion assay, respectively. TGF-β1 and cyclic adenosine monophosphate (cAMP) were quantified. EMT markers and signaling pathway were measured by RT-PCR and western blot. Results: NE stimulated TGF-β1 secretion and intracellular cAMP synthesis, induced morphological alterations in HT-29 and A549 cells, and enhanced their ability of migration and invasion. EMT markers induction was observed in NE-treated cancer cells. The effect of NE could be inhibited by propranolol or Ly2157299. β-AR/TGF-β1 signaling/p-Smad3/Snail and β-AR/TGF-β1 signaling/HIF-1α/Snail were two signaling pathways. Conclusion: These findings demonstrated that TGF-β1 signaling pathway was a significant factor of NE-induced cancer cells EMT. The data also suggested that psychological stress might be a risk factor which enhances the ability of migration or invasion of cancer cells.
    Journal of Cancer Research and Clinical Oncology 09/2015; DOI:10.1007/s00432-015-2044-9
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    ABSTRACT: Urothelial cancer associated 1 (UCA1) is a long noncoding RNA (lncRNA) which has gained more attention in recent years due to its aberrant expression in embryogenesis and a broad range of cancer tissues and cells. Importantly, multiple studies have shown that UCA1 plays oncogenic roles in tumor growth and metastasis, and it may act as a potential biomarker and therapeutic target for human cancers. However, the molecular mechanism of UCA1 in cancer initiation, progression and metastasis remains incompletely understood. Thus, gaining a better understanding of the functional mechanism of UCA1 in cancer onset and progression is of the utmost significance for evaluating the potential application of UCA1. In this review, we discuss UCA1 expression profiling, isoform, expression regulation, biological role and mechanism for UCA1 tumor-promoting effect. We further discuss the potential clinical application of UCA1 as a promising diagnostic biomarker or therapeutic target for human cancers. UCA1 functions as an oncogenic lncRNA in several malignancies, and it might become a potential biomarker or therapeutic target for human cancers.
    Journal of Cancer Research and Clinical Oncology 09/2015; DOI:10.1007/s00432-015-2042-y
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    ABSTRACT: Distant metastasis (DM) of head and neck squamous cell carcinoma (HNSCC) is not common but remains a substantial problem. Here, we evaluated factors predictive of long-term survival in HNSCC patients presenting with DM after initial definitive treatment. The medical records of patients with HNSCC who underwent definitive treatment between 2006 and 2011 were reviewed. Univariate and multivariate analyses were performed to identify clinicopathological factors associated with long-term survival after DM. Of 779 HNSCC patients, 98 (12.6 %) had DM after completion of definitive treatment, with a median time to DM of 15 months (range 1-87 months). Overall survival (OS) rates at 1 and 2 years after DM were 43.1 and 20.5 %, respectively. In multivariate analysis, hypoalbuminemia (P < 0.001, hazard ratio [HR] 3.45, 95 % confidence interval [CI] 2.01-5.92), prior or simultaneous locoregional failure events (P < 0.001, HR 2.36, 95 % CI 1.47-3.79), multisite DM (P = 0.001, HR 2.30, 95 % CI 1.42-3.72), and no salvage treatment for DM (P = 0.003, HR 2.19, 95 % CI 1.32-3.64) were independent predictors of OS after the development of DM. Seventeen (18 %) patients survived >2 years. Patients who did not have any of these risk factors had the most favorable outcomes, with a 2-year survival of 100 %. In the absence of risk factors, long-term survival can be achieved despite the development of DM after definitive treatment.
    Journal of Cancer Research and Clinical Oncology 09/2015; DOI:10.1007/s00432-015-2043-x
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    ABSTRACT: To investigate whether an association exists between a history of fertility treatments and future risk of female malignancies. A population-based study compared the incidence of long-term female malignancies in a cohort of women with and without a history of fertility treatments including in vitro fertilization (IVF) and ovulation induction (OI). Deliveries occurred between the years 1988-2013, with a mean follow-up duration of 12 years. Excluded from the study were women with known genetic predisposition for malignancies or known malignancies prior to the index pregnancy. Female malignancies were divided into specific types including ovarian, uterine, breast and cervix. Kaplan-Meier survival curve was used to estimate cumulative incidence of malignancies. Cox proportional hazard models were used to estimate the adjusted hazard ratios (HRs) for female malignancy. During the study period, 106,031 women met the inclusion criteria; 4.1 % (n = 4363) occurred in patients following fertility treatments. During the follow-up period, patients with a history of IVF treatments had a significantly increased risk of being diagnosed with ovarian and uterine cancer as compared to patients after OI and patients with no history of fertility treatments. Cox proportional hazard models were constructed for ovarian and uterine cancer separately, controlling for confounders such as maternal age and obesity. A history of IVF treatment remained independently associated with ovarian and uterine cancer (adjusted HR 3.9; 95 % CI 1.2-12.6; P = 0.022 and adjusted HR 4.6; 95 % CI 1.4-14.9; P = 0.011; respectively). IVF treatments pose a significant risk of subsequent long-term ovarian and uterine cancer.
    Journal of Cancer Research and Clinical Oncology 09/2015; DOI:10.1007/s00432-015-2035-x
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    ABSTRACT: Curative resection and adjuvant chemotherapy is the standard treatment for Stage II/III gastric cancer, and S-1 is widely used for adjuvant chemotherapy. The type 1 insulin-like growth factor receptor (IGF1R) is involved in cell proliferation and prevention of apoptosis in many tumors. We evaluated the relative expression of the IGF1R gene to determine whether such expression correlates with outcomes in patients with Stage II/III gastric cancer. We measured the expression levels of the IGF1R gene in specimens of cancer and adjacent normal mucosa obtained from 134 patients with Stage II/III gastric cancer who received curative resection and adjuvant chemotherapy with S-1. We then evaluated whether the IGF1R gene expression levels correlate with clinicopathological characteristics and outcomes. IGF1R mRNA expression levels tended to be higher in cancer tissue than in the normal adjacent mucosa (P = 0.078). Multivariate analysis showed that high IGF1R gene expression was a significant independent predictor of poor survival in Stage II/III gastric cancer after curative resection and adjuvant chemotherapy with S-1 (HR 3.681, P = 0.007). The overall survival rate was significantly lower in patients with high IGF1R gene expression than in those with low expression (P = 0.012). IGF1R overexpression is considered a useful independent predictor of outcomes in Stage II/III gastric cancer after curative resection and adjuvant chemotherapy with S-1.
    Journal of Cancer Research and Clinical Oncology 09/2015; DOI:10.1007/s00432-015-2039-6
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    ABSTRACT: The role of adjuvant radiotherapy in patients with esophageal squamous cell carcinoma (ESCC) remains controversial. This retrospective study was designed to analyze the impact of adjuvant radiotherapy in patients with T3 stage ESCC after radical resection. Data of a single-center cohort of 692 patients with T3 stage ESCC who underwent radical resection, with or without adjuvant radiotherapy, were reviewed. Univariate and multivariate analyses were performed to compare overall survival (OS) and locoregional recurrence-free survival (LRFS). Two hundred and forty-six patients received adjuvant radiotherapy (S + R group), and 446 patients underwent surgery alone (S group). The median survival time and 5-year OS rate were 40.0 months and 40.9 % for the entire population, 50.0 months and 45.6 % for the S + R group and 38.0 months and 38.3 % for the S group (P = 0.114 for S + R group vs. S group). The 5-year LRFS rate for the S + R group was significantly higher than that for S group (50.8 vs. 35.9 %, P < 0.001). In subgroup analyses, adjuvant radiotherapy was found to improve the 5-year OS in the subgroups of tumor length >5 cm, pN0 and pN1 categories, pTNM stage IIa, IIb and IIIa (P < 0.005). Adjuvant radiotherapy is effective in local control of radically resected T3 stage ESCC and may improve the overall survival in certain subgroups, such as the patients with tumor length >5 cm, pN0 and pN1 categories, pTNM stage IIa, IIb and IIIa. Further studies are required to confirm our results.
    Journal of Cancer Research and Clinical Oncology 09/2015; DOI:10.1007/s00432-015-2041-z
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    ABSTRACT: Preclinical models of chemotherapy resistance and clinical observations derived from the prospective multicenter phase III collaborative trial in relapsed aggressive lymphoma (CORAL) study demonstrated that primary refractory/relapsed B cell diffuse large B cell lymphoma has a poor clinical outcome with current available second-line treatments. Preclinically, we found that rituximab resistance is associated with a deregulation on the mitochondrial potential rendering lymphoma cells resistant to chemotherapy-induced apoptotic stimuli. There is a dire need to develop agents capable to execute alternative pathways of cell death in an attempt to overcome chemotherapy resistance. Posttranscriptional histone modification plays an important role in regulating gene transcription and is altered by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs regulate several key cellular functions, including cell proliferation, cell cycle, apoptosis, angiogenesis, migration, antigen presentation, and/or immune regulation. Given their influence in multiple regulatory pathways, HDAC inhibition is an attractive strategy to evaluate its anti-proliferation activity in cancer cells. To this end, we studied the anti-proliferation activity and mechanisms of action of suberoylanilide hydroxamic acid (SAHA, vorinostat) in rituximab-chemotherapy-resistant preclinical models. A panel of rituximab-chemotherapy-sensitive (RSCL) and rituximab-chemotherapy-resistant cell lines (RRCL) and primary tumor cells isolated from relapsed/refractory B cell lymphoma patients were exposed to escalating doses of vorinostat. Changes in mitochondrial potential, ATP synthesis, and cell cycle distribution were determined by Alamar blue reduction, Titer-Glo luminescent assays, and flow cytometric, respectively. Protein lysates were isolated from vorinostat-exposed cells, and changes in members of Bcl-2 family, cell cycle regulatory proteins, and the acetylation status of histone H3 were evaluated by Western blotting. Finally, cell lines were pre-exposed to vorinostat for 48 h and subsequently exposed to several chemotherapy agents (cisplatin, etoposide, or gemcitabine); changes in cell viability were determined by CellTiter-Glo(®) luminescence assay (Promega, Fitchburg, WI), and synergistic activity was evaluated using the CalcuSyn software. Vorinostat induced dose-dependent cell death in RRCL and in primary tumor cells. In addition, in vitro exposure of RRCL to vorinostat resulted in an increase in p21 and acetylation of histone H3 leading to G1 cell cycle arrest. Vorinostat exposure resulted in apoptosis in RSCL cell lines but not in RRCL. This finding suggests that in RRCL, vorinostat induces cell death by alternative pathways (i.e., irreversible cell cycle arrest). Of interest, vorinostat was found to reverse acquired chemotherapy resistance in RRCL. Our data suggest that vorinostat is active in RRCL with a known defective apoptotic machinery, it can active alternative cell death pathways. Given the multiple pathways affected by HDAC inhibition, vorinostat can potentially be used to overcome acquired resistant to chemotherapy in aggressive B cell lymphoma.
    Journal of Cancer Research and Clinical Oncology 08/2015; DOI:10.1007/s00432-015-2026-y
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    ABSTRACT: To examine the incidence and characteristics of metachronous contralateral breast cancer (CBC) among women in the Canton of Zurich, Switzerland. For 1980-2006, patients with unilateral invasive breast cancer (UBC) were analysed for metachronous CBC. Poisson's regression was used to estimate incidence rates of metachronous CBC according to age, year of diagnosis, follow-up period since first breast cancer and morphology. Of 16,323 patients with UBC, 700 (4.3 %) developed a second malignant tumour of the opposite breast. Median age at first breast cancer was lower in the CBC group than in the full cohort. Median interval time between first and second breast cancer was 5.5 (interquartile range 2.6-10.1) years. Incidence rate at age 20-29 was 1006 (95 % confidence interval, CI, 452-2238) cases per 100,000 person-years and decreased to 299 (199-450) at 80-84. Age-adjusted incidence rates according to period of diagnosis decreased from 618 (530-721) for 1980-1984 to 329 (217-500) cases per 100,000 person-years for 2005-2006. Incidence rate ratio of CBC for lobular carcinoma was 1.28 (95 % CI 0.99-1.67) adjusted by age group and period of diagnosis compared to ductal carcinoma. In our study, incidence rates for CBC are comparable with findings from the literature. A reduction in the incidence of metachronous CBC, thought to be due to adjuvant therapies, is seen in our data. In our cohort, younger age and lobular carcinoma were associated with an increased risk of CBC.
    Journal of Cancer Research and Clinical Oncology 08/2015; DOI:10.1007/s00432-015-2031-1
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    ABSTRACT: Microparticles (MPs) or ectosomes are small enclosed fragments (from 0.2 to 2 μm in diameter) released from the cellular plasma membrane. Several oncogenic molecules have been identified inside MPs, including soluble proteins XIAP, survivin, metalloproteinases, CX3CL1, PYK2 and other microRNA-related proteins; membrane proteins EGFR, HER-2, integrins and efflux pumps; and messenger RNAs and microRNAs miR-21, miR-27a, let-7, miR-451, among others. Studies have shown that MPs transfer their cargo to neoplastic or non-malignant cells and thus contribute to activation of oncogenic pathways, resulting in cell survival, drug resistance and cancer dissemination. This review summarizes recent findings on MP biogenesis and the role of the MPs cargo in cancer and discusses some of the RNAs and proteins involved. In addition, the discussion covers evidence of (1) how and which signaling pathways can be activated by MPs in recipient cells; (2) recipient cell-type selectivity in incorporation of proteins and RNAs transported by MPs; and (3) how upon stimulation, stromal cells release MPs, promoting resistance to chemotherapeutics and invasiveness in cancer cells.
    Journal of Cancer Research and Clinical Oncology 08/2015; DOI:10.1007/s00432-015-2029-8
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    ABSTRACT: A number of studies have demonstrated that microRNAs play a critical role in osteosarcoma progression, therapy and drug resistance. MicroRNA-202 has proven to be dysregulated in many human cancer studies. This study aimed to explore miR-202 contributions to drug resistance in osteosarcoma. miR-202 expression was measured by real-time PCR in patient tissues, cell lines or cells treated with TGF-β1, using siRNA to knock down the expression of Smad2, Smad3 and Smad4. miR-202 mimics, inhibitor and scramble siRNA were transfected into osteosarcoma cells to observe effects on cell apoptosis and drug resistance. Moreover, relationships of miR-202 level with PDCD4 were investigated by luciferase reporter assay, real-time PCR and Western blotting. We found that miR-202 is overexpressed in osteosarcoma tissues when compared with normal human osteoblasts and TGF-β1 can induce the expression of miR-202. Transfection of miR-202 mimics into osteosarcoma cell lines significantly promotes chemotherapy resistance by targeting PDCD4, a tumor suppressor which is involved in apoptosis. In contrast, transfection of miR-202 inhibitor enhances the drug sensitivity and apoptosis. This study provides new insights into miRNA-202 in osteosarcoma as a potential molecular target for chemotherapy.
    Journal of Cancer Research and Clinical Oncology 08/2015; DOI:10.1007/s00432-015-2028-9
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    ABSTRACT: Insufficient production of leukocytes, thrombocytes and erythrocytes after allogeneic peripheral blood stem cell transplantation (PBSCT) represents a life-threatening complication. In 20 adult patients with poor graft function (PGF defined as transfusion-dependent platelet counts <20,000/µl, or leukocytes <1500/µl, or transfusion-dependent anemia) and variable causes of PGF after allogeneic PBSCT, immunomagnetically selected CD34(+) stem cell boosts (SCB) from matched unrelated (n = 8), mismatched unrelated (n = 11) or haploidentical (n = 1) donors were applied without prior conditioning. Patients received a median of 4.6 × 10(6) CD34(+) cells per kilogram bodyweight (1.9-9.1 × 10(6)) and low T cell numbers (median 0.2 × 10(4), range 0.04-0.6 × 10(4)). All patients showed responses in at least one hematopoietic lineage. Engraftment for platelets, leukocytes and hemoglobin was 88, 88 and 100 % after a median of 14, 13 and 18 days, respectively. With regard to the complete cohort, 90 % (n = 18) showed an increase in platelets (median 76,500/µl, range -7000 to 223,000/µl), 95 % (n = 19) had an increase in leukocytes (median 3110/µl, range 150-13,740/µl) and 90 % (n = 18) improved with regard to hemoglobin (median 1.9 g/dl, range -0.9 to 5.1 g/dl). Due to effective T cell depletion, only one patient developed graft versus host disease (GvHD, grade III) after SCB. Patients were followed for a median of 7.5 months (1-74 months) with 11 patients being alive and disease free with normalized peripheral blood counts at the end of follow-up. CD34(+)-selected SCB are safe and effective and can durably improve PGF even in patients receiving grafts from unrelated matched or mismatched donors with low incidence of GvHD.
    Journal of Cancer Research and Clinical Oncology 08/2015; DOI:10.1007/s00432-015-2027-x
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    ABSTRACT: Adjuvant endocrine therapy (ET) is indicated in patients with steroid hormone receptor (HR)-positive breast cancer. The aim of this study was to evaluate the quality of HR determination and adjuvant endocrine treatment of breast cancer patients in a large cohort of more than 7000 women by analyzing data from a population-based regional cancer registry. Data from the Clinical Cancer Registry Regensburg (Bavaria, Germany) were analyzed. Female patients with primary, nonmetastatic invasive breast cancer who were diagnosed between 2000 and 2012 (n = 7421) were included. HR-status was available in 97.4 % (n = 7229) of the patients. This data set (n = 7229) was used for subsequent statistical analyses. Since 2009, almost a complete rate of 99.6 % of analyzed HR-status was achieved. In sum, 85.8 % of the patients (n = 6199) were HR-positive, whereas 14.2 % (n = 1030) were HR-negative. Overall, 85.3 % (n = 5285) of HR-positive patients received ET either alone or in combination with chemotherapy (CHT) and/or trastuzumab. The majority of premenopausal patients received CHT plus ET (716 patients, 52.3 %). In postmenopausal patients, the most frequent systemic therapy was ET alone (2670 patients, 55.3 %). Best overall survival (OS) was found in HER2-/HR-positive patients receiving CHT plus ET plus trastuzumab (7-year OS rate of 97.2 % in premenopausal patients versus 86.9 % in postmenopausal patients). Premenopausal patients had a reduced benefit from additional CHT than postmenopausal patients. Premenopausal patients receiving only ET had a 7-year OS rate of 95.3 % compared to 92.7 % of patients receiving CHT plus ET. In contrast, postmenopausal patients treated with CHT plus ET had a 7-year OS rate of 84.0 % in comparison with those patients receiving only ET with a 7-year OS rate of 81.7 %. Analysis of HR in patients with early breast cancer achieved a very high quality in recent years. The vast majority of HR-positive patients received ET, and this guideline-adherent use improved OS. Inverse effects of the CHT plus ET combination in premenopausal versus postmenopausal patients and a still existing minority of patients not receiving guideline-adherent treatment should be further investigated in future studies.
    Journal of Cancer Research and Clinical Oncology 08/2015; DOI:10.1007/s00432-015-2025-z
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    ABSTRACT: Pancreatic cancer shows a remarkable preference for the liver to establish secondary tumors. Selective metastasis to the liver is attributed to the development of potential microenvironment for the survival of pancreatic cancer cells. This review aims to provide a full understanding of the hepatic metastatic process from circulating pancreatic cancer cells to their settlement in the liver, serving as a basic theory for efficient prediction and treatment of metastatic diseases. A systematic search of relevant original articles and reviews was performed on PubMed, EMBASE and Cochrane Library for the purpose of this review. Three interrelated phases are delineated as the contributions of the interaction between pancreatic cancer cells and the liver to hepatic metastasis process. Chemotaxis of disseminated pancreatic cancer cells and simultaneous defensive formation of platelets or neutrophils facilitate specific metastasis toward the liver. Remodeling of extracellular matrix and stromal cells in hepatic lobules and angiogenesis induced by proangiogenic factors support the survival and growth of clinical micrometastasis colonizing the liver. The bimodal role of the immune system or prevalence of cancer cells over the immune system makes metastatic progression successfully proceed from micrometastasis to macrometastasis. Pancreatic cancer is an appropriate research object of cancer metastasis representing more than a straight cascade. If any of the successive or simultaneous phases, especially tumor-induced immunosuppression, is totally disrupted, hepatic metastasis will be temporarily under control or even cancelled forever. To shrink cancers on multiple fronts and prolong survival for patients, novel oral or intravenous anti-cancer agents covering one or different phases of metastatic pancreatic cancer are expected to be integrated into innovative strategies on the premise of safety and efficacious biostability.
    Journal of Cancer Research and Clinical Oncology 08/2015; DOI:10.1007/s00432-015-2024-0