Description

Anticancer Research (AR) publishes high quality works and reviews on all aspects of experimental and clinical cancer research. AR preferentially publishes papers advancing the understanding of cancer causation, and papers applying the results of basic research to cancer diagnosis, prognosis and therapy.

Publisher details

International Institute of Anticancer Research

Publications in this journal

• Inhibition of metastasis of circulating human prostate cancer cells in the chick embryo by an extracellular matrix produced by foreskin fibroblasts in culture.

  Authors: Rhiana Menen, Emmett Pinney, Mohamed K Hassanein, Katarina Kolostova, Vladimir Bobek, Atsushi Suetsugu, Nan Zhang, Michael Bouvet, Gail K Naughton, Robert M Hoffman

  Anticancer research. 32(5):1573-7.

  We have previously demonstrated the increased metastatic potential of human prostate cancer circulating tumor cells (CTC), compared to their parental cells, in both orthotopic mouse models and theWe have previously demonstrated the increased metastatic potential of human prostate cancer circulating tumor cells (CTC), compared to their parental cells, in both orthotopic mouse models and the chick embryo model. In the current study, we asked whether an extracellular matrix (ECM), produced by human foreskin fibroblasts in culture, could inhibit PC-3 human prostate cancer CTC metastasis in the chick embryo model. The chorioallantoic membranes (CAM) of 18 chicken embryos were inoculated with either PC-3 human prostate cancer cells or PC-3 CTCs, both stably expressing green fluorescent protein (GFP). Embryos were divided into six groups: PC-3 parental-cell control; PC-3 plus soluble ECM; PC-3 parental cells plus semi-solid ECM; PC-3 CTC control; PC-3 CTC plus soluble ECM, and PC-3 CTC plus semi-solid ECM. Twelve hours following inoculation of the cells, a single dose of 100 μl of either soluble or semi-solid ECM was added to the appropriate group. Embryo brains were removed on day 8 post-inoculation, and were processed for cryosectioning. Imaging was performed on the cryosections using a scanning laser microscope in order to count metastatic foci. PC-3 controls had an average of 11.1 metastatic foci compared to 2.55 in the PC-3 plus soluble ECM group and 2.76 (p<0.0001) in the PC-3 plus semi-solid ECM group (p<0.0001). ECM treatment had even greater efficacy on the CTC cells, with an average of 30.9 metastatic foci in the CTC controls compared to 4.38 in the CTC plus soluble ECM group (p<0.0001) and 4.18 in the CTC plus semi-solid ECM group (p<0.0001). The results demonstrate that reduction of CTC metastatic potential is possible, in this case with an ECM produced by human foreskin fibroblasts in culture.

• The Expression of HMGA2 Varies Strongly among Colon Carcinomas.

  Authors: Burkhard Maria Helmke, Dominique Nadine Markowski, Anke Meyer, Jörn Bullerdiek

  Anticancer research. 32(5):1589-93.

  The expression of high mobility group protein AT-hook2 (HMGA2) indicates a worse prognosis in many epithelial malignancies, such as colon cancer. The present study addresses methodological aspects,The expression of high mobility group protein AT-hook2 (HMGA2) indicates a worse prognosis in many epithelial malignancies, such as colon cancer. The present study addresses methodological aspects, as well as the genetic background, of the HMGA2 expression in colon cancer. Samples of 38 colon carcinomas were studied for the expression of HMGA2 by quantitative Real-Time PCR (qRT-PCR). In selected cases, immunohistochemistry (IHC) was also performed. The overexpression of HMGA2, compared to adjacent mucosa, is not consistent among colon carcinomas: Only a minority of carcinomas strongly overexpressed HMGA2, but in no more than 50% of the tumors did the expression exceed the average value in mucosa samples. qRT-PCR clearly reveals a continuum between cases with high and low expression. For HMGA2-based risk assessment, continuous rather than discontinuous models seem to be most appropriate. However, in daily practice, IHC seems to be a suitable method to stratify for high-risk patients.

• Effect of miR-34b Overexpression on the Radiosensitivity of Non-small Cell Lung Cancer Cell Lines.

  Authors: Joana Balça-Silva, Sílvia Sousa Neves, Ana Cristina Gonçalves, Ana Margarida Abrantes, João Casalta-Lopes, Maria Filomena Botelho, Ana Bela Sarmento-Ribeiro, Henriqueta Coimbra Silva

  Anticancer research. 32(5):1603-9.

  The miR-34 family, under-expressed in-non small cell lung cancers (NSCLCs), are effectors of p53 activation upon irradiation of cells. We evaluated whether the miR-34b overexpression modulates theThe miR-34 family, under-expressed in-non small cell lung cancers (NSCLCs), are effectors of p53 activation upon irradiation of cells. We evaluated whether the miR-34b overexpression modulates the NSCLCs response to radiation. NSCLC cell lines A549 with V-KI-RAS2 Kirsten Rat Sarcoma viral oncogene (KRAS) codon 12 mutation and with wild type p53, and H1299, not expressing p53, were irradiated after transfection with pre-miR-34b. Cell survival was assessed by clonogenic survival assays. The apoptosis and the cell cycle were evaluated by flow cytometry. In the A549 cell line, overexpression of miR-34b significantly reduced cell survival at lower than 4 Gy radiation doses. There was a significant reduction in B-cell CLL/lymphoma 2 (BCL2) expression but no significant differences were observed in the apoptotic cell population or the cycle profile. No significant effect was recorded in the H1299 irradiated cells. In the p53 wild type, KRAS mutated NSCLC cells, the overexpression of miR-34b increases radiosensitivity at low doses of radiation.

• Utility of Cell-free Tumour DNA for Post-surgical Follow-up of Colorectal Cancer Patients.

  Authors: Miroslav Levy, Lucie Benesova, Ludmila Lipska, Barbora Belsanova, Petra Minarikova, Gabriela Veprekova, Miroslav Zavoral, Marek Minarik

  Anticancer research. 32(5):1621-6.

  While efficient surgical treatment is the key to prolonged survival of patients with colorectal cancer, post-surgical follow-up is important for the early detection of relapsing disease or of diseaseWhile efficient surgical treatment is the key to prolonged survival of patients with colorectal cancer, post-surgical follow-up is important for the early detection of relapsing disease or of disease progression. Current dispensarization, typically based on imaging CT, PET, MR, is frequently supported by the observation of tumour markers (CEA, CA19-9). Due to their limited sensitivity and selectivity, better tools for monitoring of the disease are desirable. Tumour cell-free DNA (cfDNA) has been recently demonstrated as a new promising molecular marker for observation and early detection of disease progression. We present results of post-surgical monitoring tumour cfDNA in the cases of seven patients suffering from advanced forms of CRC. We applied a mutation-based approach in which the total cfDNA was screened for a specific somatic mutation present in the primary tumour. We screened a panel of the most frequent somatic mutations covering the genes APC, KRAS, TP53, PIK3CA and BRAF. All patients were tested positive for tumour cfDNA prior to surgery. cfDNA was then evaluated within a week after surgery and subsequently in monthly intervals. We present typical cases of colorectal cancer patients who underwent surgical treatment at different levels of radicality with or without adjuvant chemo/biotherapy. The tumour cfDNA status was found to be always closely correlated with the actual clinical status of the patient. The cfDNA appears to be a viable tool for the monitoring of the clinical progression of CRC in patients with cfDNA positivity prior to surgery.

• EGFR and P-GP Expression in Oropharyngeal Mucosa in Relation to Smoking.

  Authors: Philipp Baumeister, Melanie Märte, Maximilian Reiter, Christian Welz, Sabina Schwenk-Zieger, Ulrich Harréus

  Anticancer research. 32(5):1639-48.

  About two thirds of head and neck squamous cell carcinoma (HNSCC) cases are attributable to heavy tobacco and alcohol consumption. Tobacco carcinogens cause cellular damage in large areas of theAbout two thirds of head and neck squamous cell carcinoma (HNSCC) cases are attributable to heavy tobacco and alcohol consumption. Tobacco carcinogens cause cellular damage in large areas of the upper aerodigestive tract mucosa and contribute to distinct molecular changes, such as increasing levels of epidermal growth factor receptor (EGFR), during carcinogenesis. P-Glycoprotein (P-GP) is a multidrug-resistance transporter protein capable of extruding not only cytotoxic drugs, but also certain tobacco-related carcinogens. EGFR plays a major role in the transcriptional and functional regulation of P-GP and previous studies in our laboratory showed that stimulation of EGFR protection protected oropharyngeal cells from a carcinogen that is substrate of P-GP. Therefore, we evaluated expression levels of EGFR and P-GP and looked for a possible association with the smoking status of patients. Tissue cultures of healthy oropharyngeal mucosa were produced from 30 patients undergoing surgery at our Department. Expression levels of EGFR on P-GP were determined by immunohistochemical staining. To evaluate possible influences of EGFR on P-GP expression, we stimulated the receptor using transforming growth factor alpha (TGF-α) for 24, 48 and 72 h. Current and former smokers had significantly higher EGFR/P-GP levels than never smokers. While EGFR expression was detected in almost all samples, P-GP expression was largely restricted to former and current smokers. TGF-α had no detectable effect on EGFR/P-GP levels. These results show an association between tobacco use and levels of both proteins. Since both these proteins are involved in drug resistance of head and neck cancer, this study might help to further understand the differences in response to therapy and prognosis of tobacco-related and -unrelated cancer.

• Sub-toxic Cisplatin Mediates Anoikis Resistance through Hydrogen Peroxide-induced Caveolin-1 Up-regulation in Non-small Cell Lung Cancer Cells.

  Authors: Thitiporn Songserm, Varisa Pongrakhananon, Pithi Chanvorachote

  Anticancer research. 32(5):1659-69.

  Exposure to inadequate chemotherapy may alter cancer cell behavior including their metastatic potential. Because the molecular basis of such a phenomenon is largely unclear, we investigated theExposure to inadequate chemotherapy may alter cancer cell behavior including their metastatic potential. Because the molecular basis of such a phenomenon is largely unclear, we investigated the possible impact of cisplatin on anoikis response on human lung carcinoma cells. Using molecular and pharmacological tools, Caveolin-1 (CAV1) overexpressing and knock-down H460 cells were generated by stable transfection. The levels of CAV1 were determined by western blotting and reactive oxygen species (ROS) were detected by specific probes. Sub-toxic concentrations of cisplatin suppressed anoikis response in H460 cells. The anoikis attenuation observed, was found to be caused by CAV1 up-regulation. Exposure to cisplatin induced superoxide anion and hydrogen peroxide generation; however, only hydrogen peroxide was found to be responsible for the CAV1 elevation. Exposure to cisplatin at sub-toxic concentrations induced hydrogen peroxide generation and the subsequent increase of ROS further regulated CAV1 levels and anoikis resistance. Our findings demonstrate a novel effect of cisplatin treatment on cancer cells which may lead to a better understanding of cancer biology and in the improvement of chemotherapy.

• The Survivin Suppressant YM155 Potentiates Chemosensitivity to Gemcitabine in the Human Pancreatic Cancer Cell Line MiaPaCa-2.

  Authors: Dok Hyun Yoon, Jae-Sik Shin, Dong-Hoon Jin, Seung-Woo Hong, Kyung A Jung, Seung-Mi Kim, Yong Sang Hong, Kyu-Pyo Kim, Jae-Lyun Lee, Cheolwon Suh, Jung Shin Lee, Tae Won Kim

  Anticancer research. 32(5):1681-8.

  Survivin is a negative regulator of apoptosis. We evaluated the efficacy of YM155, a selective suppressant of survivin, in combination with gemcitabine in the pancreatic cancer cell lineSurvivin is a negative regulator of apoptosis. We evaluated the efficacy of YM155, a selective suppressant of survivin, in combination with gemcitabine in the pancreatic cancer cell line MiaPaCa-2. Expression of survivin was demonstrated by immunoblotting. Cell cycle progression was determined by flow cytometric analysis. Cell viability was assayed using the trypan blue exclusion assay. Gemcitabine up-regulated survivin expression, whereas treatment with YM155 suppressed the expression of survivin. Concomitant treatment with YM155 enhanced chemosensitivity to gemcitabine, which was accompanied by a decrease in the expression of survivin. Knockdown of endogenous survivin via RNA interference also enhanced the sensitivity to gemcitabine. In addition, YM155 potentiated the antitumor effect of gemcitabine in xenograft tumors of MiaPaCa-2. YM155 potentiates chemosensitivity to gemcitabine in pancreatic cancer cells by suppressing the induction of survivin. Combination treatment with gemcitabine and YM155 may be a potential therapeutic strategy for the treatment of pancreatic cancer that warrants further clinical investigation.

• Olfactory neuroblastoma: 15 years of experience.

  Authors: Norio Kondo, Hideaki Takahashi, Yoko Nii, Junichi Nagao

  Anticancer research. 32(5):1697-703.

  Olfactory neuroblastoma is a rare malignant neoplasm of the nasal cavity and of the paranasal sinus. In the treatment of patients with advanced olfactory neuroblastoma, the combination ofOlfactory neuroblastoma is a rare malignant neoplasm of the nasal cavity and of the paranasal sinus. In the treatment of patients with advanced olfactory neuroblastoma, the combination of craniofacial resection with radiotherapy and/or chemotherapy has significantly improved the survival rate. However, locoregional recurrence and distant metastasis frequently occur, irrespective of the aggressiveness of therapy. We report our experience on the outcomes of olfactory neuroblastoma in patients treated with concurrent chemoradiotherapy (CCRT). We retrospectively analyzed the cases of seven patients with olfactory neuroblastoma, treated in the past 15 years. Six patients were treated with CCRT, consisting of cisplatin (60 mg/m(2), day 4), 5-fluorouracil (600 mg/m(2), given over 24 h for 5 days, days 1-5), methotrexate (30 mg/m(2), day 1) and leucovorin (20 mg/m(2), days 1-5) (PFML). One patient was treated with radiotherapy and neoadjuvant chemotherapy, which consisted of a combination of three drugs: cyclophosphamide (360 mg/m(2), day 1), cisplatin (60 mg/m(2), day 4), 5-fluorouracil (600 mg/m(2), given over 24 h for 5 days, days 1-5) (PFC). Salvage surgery was performed in the primary remaining site. The overall 5-year survival rates were 3/6 for patients treated with CCRT using PFML and 2/5 for patients with Kadish stage C olfactory neuroblastoma. The locoregional response rate was 4/6. In our limited experience, CCRT with PFML had therapeutic efficacy as a primary treatment, while surgical treatment and postoperative radiotherapy have been the main treatment modalities.

• Classification of Gastritis in First-degree Relatives of Patients with Gastric Cancer in a High Cancer-risk Area in Italy.

  Authors: Calogero Saieva, Carlos A Rubio, Gabriella Nesi, Enzo Zini, Alessandro Filomena

  Anticancer research. 32(5):1711-6.

  Screening gastroscopic examinations were performed in a cohort of individuals at high risk for developing gastric carcinoma (GC). Five gastric biopsies were obtained following the Houston schema.Screening gastroscopic examinations were performed in a cohort of individuals at high risk for developing gastric carcinoma (GC). Five gastric biopsies were obtained following the Houston schema. Five histological parameters of gastritis were investigated: acute gastritis, chronic gastritis, and its sequelae; mucosal atrophy, intestinal metaplasia and pseudopyloric metaplasia. Out of 134 patients, 50% (n=67) had Helicobacter pylori (HP) infection. The sum of scores for the first four parameters was significantly higher in HP-positive cases than in HP-negative ones (p<0.0001). The frequency of these histological parameters was similar to other series from Northern and Central Italy. Hence, none of the histological parameters of gastritis explain the high GC risk in this borough of Florence, considering that the incidence rate of GC is higher in Central than in Northern Italy. Similarities in the frequency of chronic gastritis and sequelae in Northern and Central Italy substantiate the conviction that the difference in GC risk in these regions might be the result of local environmental or lifestyle factors, rather than HP infection. This knowledge is crucial, considering that environmentally related diseases are theoretically preventable.

• Oncological Short-term Effects and Adverse Events of MRI-guided Selective Neoadjuvant Radiochemotherapy for Rectal Cancer.

  Authors: C A Maurer, D Mattiello, J Duwe, R Ruppert, H Ptok, J Strassburg, T Junginger, S Merkel, P Hermanek

  Anticancer research. 32(5):1721-8.

  Aim: To investigate the oncological short-term effects and acute side-effects of magnetic resonance imaging (MRI)-guided selective neoadjuvant radiochemotherapy (nRCT) for rectal cancer. In aAim: To investigate the oncological short-term effects and acute side-effects of magnetic resonance imaging (MRI)-guided selective neoadjuvant radiochemotherapy (nRCT) for rectal cancer. In a prospective multicenter cohort study of 230 patients with rectal cancer stage II or III, nRCT was applied in the following situations (n=96) only: cT4 tumors, cT3 tumors of the distal rectum or tumors leaving a circumferential resection margin (CRM) of ≤1 mm between the tumor and the mesorectal fascia (mrCRM+). Pre-therapeutical tumor stage and involvement of mesorectal fascia were assessed by MRI and were compared with the pathological findings of the rectal specimens. Furthermore, tumor regression grades, acute side-effects, and surgical complications were analysed. Using selective nRCT, 62 out of 72 patients (86%) with mrCRM+ had tumor-negative pathological CRM. Reduction of T category was observed in 62% and of N category in 88% of patients. Lymph node metastasis was found by pathology in only 21% of all irradiated patients. Histologically complete tumor regression (ypT0ypN0) was observed in 15% and intermediate regression (more than 25%, but not complete) in 67% of patients. Fifteen percent of patients suffered from grade 3 toxicity, but no grade 4 toxicity occurred. nRCT did not adversely influence surgical morbidity. Despite the negative selection of locally advanced rectal cancer cases for nRCT, impressive rates of tumor down-staging and eradication of tumor from the mesorectal fascia were achieved. The rate of complete regression is comparable to that in the literature. Moreover, the selective use of nRCT spared a considerable percentage of patients with stage II/III rectal cancer severe irradiation toxicity.

• Vaginal fistula in a patient with relapsed ovarian cancer and amelanotic melanoma.

  Authors: Mustafa Zelal Muallem, Sule Yildiz, Ruza Arsenic, Uwe Trefzer, Jalid Sehouli

  Anticancer research. 32(5):1737-42.

  BACKGROUND: Malignant vaginal melanoma is extremely rare and accounts for fewer than 0.3% of all melanomas in women. Amelanotic malignant melanoma is a subtype of melanoma with little or no pigmentBACKGROUND: Malignant vaginal melanoma is extremely rare and accounts for fewer than 0.3% of all melanomas in women. Amelanotic malignant melanoma is a subtype of melanoma with little or no pigment on visual inspection. The simultaneous occurrence of amelanotic melanoma of the vagina and serous ovarian cancer is extremely rare. Case Report: A 61-year-old patient was referred to our hospital with recurrent ovarian cancer in association with a vaginorectal fistula. The first diagnosis was performed in 2009. The patient underwent multi-ovarian cancer recurrences after the primary cytoreductive surgery, especially in the vaginal vault, with several different lines of chemotherapy. The pathological results on this occasion demonstrated recurrent ovarian cancer with a component of amelanotic melanoma in the region of a vaginorectal fistula. CONCLUSION: We recommend detailed immunohistochemical staining, especially for recurrent ovarian cancer in combination with abnormal localizations or manifestations, in order to reveal any associations with another tumor.

• Decrease of CD44-positive Cells Correlates with Tumor Response to Chemotherapy in Patients with Gastrointestinal Cancer.

  Authors: Vindhya Palagani, Mona El Khatib, Till Krech, Michael P Manns, Nisar P Malek, Ruben R Plentz

  Anticancer research. 32(5):1747-55.

  Background/Aim: CD44 is a multistructural and multifunctional cell surface molecule which is involved in cell proliferation, differentiation, migration and angiogenesis. Here we investigated theBackground/Aim: CD44 is a multistructural and multifunctional cell surface molecule which is involved in cell proliferation, differentiation, migration and angiogenesis. Here we investigated the potential role of CD44 in patients with metastasized pancreatic ductal adenocarcinoma, colorectal and stomach cancer, which were treated with different combinations of palliative chemotherapy. CD44 expression was measured by flow cytometry in patients' (n=15) blood samples and the findings were correlated with CA19-9 expression and with computed tomography results. We found a significant correlation (p<0.05) between the CD44 decrease and the tumor response according to the tumor marker elevation/ response evaluation criteria in solid tumors. We were able to monitor changes of CD44 expression after chemotherapy and detected a correlation between the CD44 decrease and the patients' response to treatment. Our findings show that CD44 detection helps to monitor chemotherapy response in patients with gastrointestinal cancer.

• The Relationship Between Antitumor Effects and Relative Dose Intensity of S-1 plus Cisplatin Treatment for Metastatic Gastric Cancer.

  Authors: Mika Kitagawa, Takaya Shimura, Tomonori Yamada, Masahide Ebi, Yoshikazu Hirata, Tsutomu Mizoshita, Satoshi Tanida, Hiromi Kataoka, Takeshi Kamiya, Takashi Joh

  Anticancer research. 32(5):1763-8.

  Background/Aim: S-1 plus cisplatin is the standard first-line chemotherapy for metastatic gastric cancer (MGC) in Japan, but the relationship between dose intensity and antitumor effects remainsBackground/Aim: S-1 plus cisplatin is the standard first-line chemotherapy for metastatic gastric cancer (MGC) in Japan, but the relationship between dose intensity and antitumor effects remains unclear. We retrospectively studied 64 patients who received S-1 plus cisplatin for MGC from January 2006 to December 2010 in two Japanese hospitals. The median relative dose intensity (RDI) of S-1 plus cisplatin was 87% (range, 59.5%-100%). The cut-off value of RDI of S-1 plus cisplatin was identified to be 80% by a receiver operating characteristic analysis of the tumor response. In the RDI<80% (n=19) and the RDI≥80% (n=45) groups, the response rates were 20.0% and 37.5% (p=0.182), the median survival times were 394 and 376 days (p=0.915), and the median progression-free survival (PFS) was 188 and 170 days (p=0.851), respectively. An appropriate RDI reduction may be permitted for patients with MGC in palliative settings.

• A KIT-negative, DOG1-positive Epithelioid GIST of the Stomach Harboring a Novel PDGFRA Exon 14 Single Nucleotide Deletion.

  Authors: Clara Rizzardi, Stefania Marzinotto, Claudio Avellini, Mauro Melato, Laura Mariuzzi

  Anticancer research. 32(5):1775-8.

  Gastrointestinal stromal tumors (GISTs) are the most common primary mesenchymal tumors of the gastrointestinal tract, and most of them harbor KIT or platelet-derived growth factor receptor alphaGastrointestinal stromal tumors (GISTs) are the most common primary mesenchymal tumors of the gastrointestinal tract, and most of them harbor KIT or platelet-derived growth factor receptor alpha (PDGFRA) gain-of-function mutations. Proper diagnostic assessment of GISTs has become very important since the availability of the molecular-targeted therapy with imatinib mesylate. Histopathology remains the gold standard in GIST diagnosis, and immunohistochemistry plays the major confirmatory role. Moreover, genetic sequencing not only further confirms the diagnosis of GIST, but also provides information for the optimal treatment of patients. Herein, we describe a gastric GIST harboring a novel PDGFRA exon 14 frameshift mutation caused by a single-nucleotide deletion. The case reported here represents further evidence regarding the existence of a distinct subset of GISTs characterized by the PDGFRA mutation, the gastric localisation, the epithelioid morphology, and the weak or negative immunohistochemical expression of KIT. DOG1 is emerging as a promising biomarker for this subgroup of GISTs.

• Airway stenting for malignant respiratory complications in esophageal cancer.

  Authors: Yoichi Hamai, Jun Hihara, Manabu Emi, Yoshiro Aoki, Yoshihiro Miyata, Morihito Okada

  Anticancer research. 32(5):1785-90.

  Airway stenting is required for the palliative treatment of advanced esophageal cancer. This study retrospectively analyzes the outcomes of airway stenting for esophageal cancer at our institution.Airway stenting is required for the palliative treatment of advanced esophageal cancer. This study retrospectively analyzes the outcomes of airway stenting for esophageal cancer at our institution. Data from nine patients who underwent airway stenting were reviewed. All patients had poor respiratory status due to esophagorespiratory fistula and/or respiratory stenosis. We retrospectively assessed the results of airway stenting as five grades of respiratory symptoms, regarding stent-related complications and clinical course and survival. Six silicone and six covered self-expandable metallic stents were deployed in five and six patients, respectively. Two types of airway stents were deployed in two patients, and double stents were positioned in the airway and in the esophagus of three other patients. The grade of respiratory symptoms improved in seven patients. The mean dyspnea grade was 3.0±0.9 and 1.3±1.3 before and after airway stenting, respectively. Stent-related complications comprised of chest pain, incomplete closure of the ERF, sputum retention and stent migration. The mean±SD survival of all patients was 103±108 (range, 0 to 325) days, and the survival of patients without relapsed cancer at the time of stenting, who underwent cancer-specific therapy after stenting, was prolonged. Although the airway should be stented according to the status and the prognosis of each patient individually stenting can relieve symptoms and improve the prognosis even when esophageal cancer is at very advanced stages. Airway stenting could play a role in the multidisciplinary management of advanced esophageal cancer.

• Serum amyloid a: a biomarker for renal cancer.

  Authors: Kersten Fischer, Gerit Theil, Raschid Hoda, Paolo Fornara

  Anticancer research. 32(5):1801-4.

  Background/Aim: Serum amyloid A (SAA) has been identified as a potential biomarker for renal cell carcinoma. We examined its diagnostic value in patients of different tumor stages. In our study, 48Background/Aim: Serum amyloid A (SAA) has been identified as a potential biomarker for renal cell carcinoma. We examined its diagnostic value in patients of different tumor stages. In our study, 48 patients with localized and 67 patients with advanced renal tumors were included. 24 patients served as a control group. Interleukine 6 (IL-6), C-reactive protein (CRP) and SAA levels were measured preoperatively and at day 5 after nephrectomy. The IL-6, CRP and SAA levels in patients with advanced tumors are significantly higher than those of patients with localized tumors. Advanced tumors were identified with a sensitivity of 78% (SAA), 69% (CRP) and 44% (IL-6). The specificity was 82%, 82% and 94% for SAA, CRP and IL-6, respectively. Our results indicate that advanced renal cancers are accompanied by increased levels of acute-phase proteins such as CRP and SAA. SAA is found to be more sensitive than CRP for the indication of advanced renal cancer.

• Prognostic factors and clinical outcome of patients with lung adenocarcinoma with carcinomatous meningitis.

  Authors: Yukiko Nakamura, Toshiaki Takahashi, Asuka Tsuya, Tateaki Naito, Hirotsugu Kenmotsu, Akira Ono, Takehito Shukuya, Haruyasu Murakami, Hideaki Harada, Reiko Watanabe, Masahiro Endo, Koichi Mitsuya, Takashi Nakajima, Nobuyuki Yamamoto

  Anticancer research. 32(5):1811-6.

  In recent years, the incidence of carcinomatous meningitis (CM) in lung adenocarcinoma has been rising. However, it remains unclear which treatment strategies improve the outcome of theseIn recent years, the incidence of carcinomatous meningitis (CM) in lung adenocarcinoma has been rising. However, it remains unclear which treatment strategies improve the outcome of these patients. We retrospectively reviewed data for 67 lung adenocarcinoma patients diagnosed with CM between September 2002 and March 2011 in order to identify factors which would improve prognosis. In multivariate analysis, the female gender, a good performance status (PS) 0-2 and the mutant epidermal growth factor receptor (EGFR) gene were identified as factors associated with a favorable prognosis. The survival time was significantly prolonged for patients treated with EGFR-tyrosine kinase inhibitors (TKIs) (240 vs. 57 days, p<0.0001) and for patients who underwent radiotherapy of the central nervous system (CNS) (201 vs. 76 days, p=0.0038) after diagnosis of CM. The median survival time (MST) of patients treated with gefitinib before diagnosis of CM and with erlotinib after diagnosis was significantly longer than the MST of patients treated with gefitinib both before and after the diagnosis of CM (407 vs. 205 days, p=0.0015). Patients treated with both radiotherapy for CNS and EGFR-TKI had longer survival compared to patients without radiotherapy for the CNS (379 vs. 122 days, p=0.032). EGFR-TKI combined with radiotherapy may be a therapeutic approach capable of improving the prognosis of patients with lung adenocarcinoma with CM harboring the EGFR gene mutation.

• Treatment Strategies for Well-differentiated Liposarcomas and Therapeutic Outcomes.

  Authors: Norio Yamamoto, Katsuhiro Hayashi, Yoshikazu Tanzawa, Hiroaki Kimura, Akihiko Takeuchi, Kentaro Igarashi, Hiroyuki Inatani, Shingo Shimozaki, Seiko Kitamura, Hiroyuki Tsuchiya

  Anticancer research. 32(5):1821-5.

  This study examined 45 patients with well-differentiated liposarcoma who were surgically treated at our hospital (initial surgery in 41 patients and reoperation in 4). Only one patient had recurrenceThis study examined 45 patients with well-differentiated liposarcoma who were surgically treated at our hospital (initial surgery in 41 patients and reoperation in 4). Only one patient had recurrence among patients who underwent initial surgery, and the recurrence was localised in the retroperitoneal space. For patients who underwent reoperation, the mean time between the initial surgery and the recurrence was 16.5 years. None of the 45 patients developed distant metastasis. It is important to preserve not only neurovascular bundles but also lower limb muscles in order to maintain ambulatory ability in the elderly patients. For well-differentiated liposarcomas of the limbs, it is important to establish a surgical margin beyond the marginal resection border and to perform muscle resection to the extent that would not greatly reduce the muscle strength.

• Salvage Chemotherapy with Cisplatin and 5-Fluorouracil in Metastatic Breast Cancer. Particular Activity against Liver Metastases.

  Authors: Lazaros Lekakis, Dimitrios Tryfonopoulos, Nikolaos Pistamatzian, Christos Panopoulos, George Koumakis, Stamatina Demiri, Anna Efremidis

  Anticancer research. 32(5):1833-7.

  The prognosis of patients with metastatic breast cancer who have failed to respond to at least two different chemotherapy regimens is poor. Such patients with metastatic disease to the liver haveThe prognosis of patients with metastatic breast cancer who have failed to respond to at least two different chemotherapy regimens is poor. Such patients with metastatic disease to the liver have even worse prognosis. Cisplatin and 5-fluorouracil (5-FU) can be given in patients with impaired hepatic function but their combination has not been extensively studied in this setting. We retrospectively collected data from our registry on patients with advanced metastatic breast cancer who received combination of cisplatin/5-FU. We sought to determine the toxicity, the response rate, the disease control rate and the survival of this combination. We identified 25 heavily pre-treated patients, out of which 19 (76%) had liver metastases. They had been treated before with a median of three lines of cytotoxic chemotherapy. The majority of patients had also received hormonal manipulation or trastuzumab. The median number of cisplatin/5-FU administered cycles, without toxic deaths or unexpected toxicities was four. The partial response (PR) rate was 32% and the disease control rate (DCR) was 68%. The time to progression was five months and the median survival after starting on cisplatin/5-FU was six months. The combination of cisplatin/5-FU is active and safe in heavily pre-treated patients with metastatic breast cancer even in the presence of liver metastases and jaundice.

• Cytokeratin serum biomarkers in patients with colorectal cancer.

  Authors: S Holdenrieder, P Stieber, V Liska, V Treska, O Topolcan, J Dreslerova, V M Matejka, J Finek, L Holubec

  Anticancer research. 32(5):1971-6.

  Circulating cytokeratins have shown to be important for management of patients with lung cancer. Here we investigated their role for differential diagnosis, therapy monitoring and prognosis inCirculating cytokeratins have shown to be important for management of patients with lung cancer. Here we investigated their role for differential diagnosis, therapy monitoring and prognosis in colorectal cancer (CRC). Pretherapeutic levels of cytokeratin-19 fragments (CYFRA 21-1), carcino-embryonic antigen (CEA) and cancer antigen (CA) 19-9 were measured in 42 patients with CRC, 45 with benign colorectal diseases and 51 healthy controls. Furthermore, courses of CYFRA 21-1, tissue polypeptide antigen (TPA), tissue polypeptide specific antigen (TPS), M30-antigen, CEA and CA 19-9 were analyzed in prospectively collected sera of 15 patients with CRC during primary chemotherapy and were correlated with therapy response and overall survival (OS). Similar to CEA and CA 19-9, CYFRA 21-1 was significantly elevated in serum from patients with CRC (median 2.1 ng/ml) as compared with healthy (1.2 ng/ml; p<0.0001) and benign gastrointestinal controls (1.7 ng/ml; p=0.0178) and showed stage dependency in CRC (p=0.0118). CYFRA 21-1 correlated with CEA in benign diseases and CRC but not with CA 19-9. The best discrimination between healthy controls and patients with CRC was achieved by combination of CYFRA 21-1 and CA 19-9 (area under the curve; AUC=86.7%), while the combination of CEA and CA 19-9 discriminated best between benign diseases and CRC (AUC=73.9%). In CRC patients during primary chemotherapy, levels of cytokeratins CYFRA 21-1, TPA, TPS, CEA and CA 19-9 tended to be higher in patients with poor response to therapy and with poor prognosis. Cytokeratins are elevated in patients with CRC and show some association with response to primary therapy and prognosis.

• Real-time Cell Analysis of Human Cancer Cell Lines after Chemotherapy with Functionalized Magnetic Nanoparticles.

  Authors: Stephan Dürr, Stefan Lyer, Jenny Mann, Christina Janko, Rainer Tietze, Eveline Schreiber, Martin Herrmann, Christoph Alexiou

  Anticancer research. 32(5):1983-9.

  Magnetic drug targeting is a new and innovative approach in cancer treatment. In order to avoid the adverse effects of chemotherapy, the therapeutic agent is linked to superparamagnetic nanoparticlesMagnetic drug targeting is a new and innovative approach in cancer treatment. In order to avoid the adverse effects of chemotherapy, the therapeutic agent is linked to superparamagnetic nanoparticles which are injected into a tumour-supporting artery and is focused by an external magnetic field to the tumour region in order to provoke maximum local impact. Analysis of nanoparticles and chemotherapeutic substances in human cancer cell culture is necessary to provide respective information for in vivo applications. The effect of pure mitoxantrone and mitoxantrone bound to nanoparticles was tested on human cancer cell lines using real-time cell analysis (RTCA) and lactate dehydrogenase (LDH) assays. RTCA was performed by impedance measuring. The impedance is expressed as the cell index (CI), which is a parameter of cell viability. RTCA showed that mitoxantrone when bound to nanoparticles was more toxic than the drug alone. The CI clearly decreased faster after adding the chemotherapeutic bound to nanoparticles than when adding the pure drug alone. However, in the first experiments, the particles themselves showed no toxicity at therapeutically relevant concentrations. These results were confirmed by LDH assays. The toxic effects of chemotherapeutic agents (e.g. mitoxantrone) on human cancer cell lines (e.g. MCF-7) can be enhanced if these drugs are bound to magnetic nanoparticles. These preliminary data show a dependency on the different application modes of RTCA. The results presented here are a first step for a better understanding of the effectiveness of magnetic drug targeting as a new and innovative cancer treatment.

• Surgery for advanced and metastatic pancreatic cancer - current state and trends.

  Authors: Michael F Nentwich, Maximilian Bockhorn, Alexandra König, Jakob R Izbicki, Güllü Cataldegirmen

  Anticancer research. 32(5):1999-2002.

  Due to the late onset of symptoms in pancreatic cancer, patients are often presented with an already advanced or metastatic state of disease. Only in a minority of patients is a tumor resectionDue to the late onset of symptoms in pancreatic cancer, patients are often presented with an already advanced or metastatic state of disease. Only in a minority of patients is a tumor resection indicated, e.g. in general tumor encasement of major vessels, while the presence of metastatic disease excludes patients from curative-intended surgery. Limitations for pancreatic resections have been debated and re-thought after more experience has gained over time. This holds true for en-bloc vascular resections, total pancreatectomies, intentional R2 pancreatic resections and synchronous resection of liver metastases. These issues are addressed in this review.

• Circulating microparticles in patients with benign and malignant ovarian tumors.

  Authors: A Rank, S Liebhardt, J Zwirner, A Burges, R Nieuwland, B Toth

  Anticancer research. 32(5):2009-14.

  Microparticles are known to be increased in various malignancies. In this prospective study, microparticle levels were evaluated in patients with benign and malignant ovarian lesions. MicroparticlesMicroparticles are known to be increased in various malignancies. In this prospective study, microparticle levels were evaluated in patients with benign and malignant ovarian lesions. Microparticles from platelets/megakaryocytes, activated platelets and endothelial cells, tissue factor exposing microparticles and D-dimer values were examined in patients with newly diagnosed ovarian lesions before surgery, and were correlated with tumor histology. Higher counts of CD63-positive microparticles were detected in patients with ovarian cancer [mean=276×10(6) (range: 64-948)/l; n=12] as compared to patients with benign ovarian tumors [146×10(6) (45-390)/l; n=21; p=0.014]. D-dimer values were also increased in patients with cancer [860 (180-4500) ng/l versus 280 (170-2720) ng/l; p=0.001]. Elevated levels of CD63-positive microparticles and D-dimer reflect the procoagulant phenotype of these patients. However, for the discrimination between benign and malignant ovarian tumors, measuring preoperative levels of microparticles does not seem to be helpful.

• Expression of podoplanin in primary and metastatic poorly differentiated and undifferentiated carcinomas of the head and neck.

  Authors: Reinhard E Friedrich, Sylva Bartel-Friedrich, Christian Hagel

  Anticancer research. 32(5):2019-22.

  The invasive growth properties of head and neck carcinoma can be determined by proteins associated with cellular motility. Podoplanin is a recently identified protein associated with motility ofThe invasive growth properties of head and neck carcinoma can be determined by proteins associated with cellular motility. Podoplanin is a recently identified protein associated with motility of cells. Sixty-five tumour specimens of 51 patients with poorly and undifferentiated carcinomas were investigated for podoplanin expression. All tissues were fixed in buffered formalin and embedded in paraffin. Podoplanin expression showed a tendency towards a more intense staining in carcinomas with a squamous epithelia differentiation compared to tumours without any remnants of cellular layers. Podoplanin expression was very rarely seen in lymph node metastases and the staining was weak in these specimens. The differences of podoplanin expression between primary and metastatic carcinoma were highly significant (p<0.005). Podoplanin is expressed in primary undifferentiated carcinoma, both inside and outside of Waldeyer's ring. This study shows that podoplanin can be used as a marker of tumour invasion in poorly or undifferentiated head and neck carcinoma.

• Similar Incidences of TP53 Deletions in Extramedullary Organ Infiltrations, Soft Tissue and Osteolyses of Patients with Multiple Myeloma.

  Authors: Lisa Billecke, Eva Maria Murga Penas, Annette M May, Monika Engelhardt, Arnon Nagler, Merav Leiba, Ginette Schiby, Nicolaus Kröger, Jozef Zustin, Andreas Marx, Jakob Matschke, Markus Tiemann, Eray Goekkurt, Carsten Bokemeyer, Georgia Schilling

  Anticancer research. 32(5):2031-4.

  Extramedullary (EM) organ impairment in patients with multiple myeloma (MM) is a rare event, occurring mostly during disease relapse after high-dose chemotherapy with autologous or allogeneic stemExtramedullary (EM) organ impairment in patients with multiple myeloma (MM) is a rare event, occurring mostly during disease relapse after high-dose chemotherapy with autologous or allogeneic stem cell transplantation. This manifestation is commonly associated with an unfavourable outcome. Previous studies suggested a correlation between the clinical course of patients with MM and EM and the cytogenetic findings, e.g. deletion of TP53 on 17p13. We investigated patients with these rare plasma cell organ infiltrations (n=17) as well as bone lesions or soft tissue lesions, known to be a common clinical feature of MM (n=14), using a newly established method of fluorescence in situ hybridization in combination with cytoplasmic immunoglobulin staining (cIg-FISH) on paraffin-embedded sections and a specific probe for TP53 on 17p13. Results and The incidence of del(17)(p13) was similar in both groups but overall it was higher when compared to published data obtained from bone marrow samples and material originating from osteolyses. Further investigations on a larger patient cohort are needed in order to confirm these findings.

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