Journal of experimental & clinical cancer research: CR (J Exp Clin Canc Res )


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    Journal of experimental & clinical cancer research, Journal of experimental and clinical cancer research, CR, C.R
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Publications in this journal

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    ABSTRACT: ABSTRACT: There are no reports in the literature of acute pancreatitis after "one shot" percutaneous ethanol injection (PEI); in contrast, cases of lethal acute pancreatitis are described as a complication of intraarterial PEI. We report a case of a lethal necrotizing pancreatitis resulting from a "one shot" PEI into a multifocal hepatocellular carcinoma (HCC). Deaths after PEI occur between a few hours and a few days after the event because of hemoperitoneum and haemorrhage from oesophageal varices and the major complications are renal insufficiency, hemoperitoneum and hepatic insufficiency. None of these complications occurred in our patient immediately after PEI. We believe that PEI initially caused the edematous pancreatitis through a detrimental metabolic effect. Thereafter, the ensuing treatment with opioids (to reduce the patient's abdominal pain) led to toxic effects causing, together with PEI, the development of lethal necrotizing pancreatitis.
    Journal of experimental & clinical cancer research: CR 07/2008; 27(1):12.
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    Journal of experimental & clinical cancer research: CR 04/2008; 27(1):1.
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    ABSTRACT: Angiogenesis is an essential process for progression of hepatocellular carcinoma (HCC). The alpha-chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 have been recognized for their roles in regulating neoangiogenesis. The role of SDF-1 and CXCR4 in HCC progression has been little analyzed. The study aims to evaluate immunohistochemical expression of the SDF-land CXCR4 in HCC tissue and non-HCC tissue. Formalin-fixed paraffin-embedded tissue sections of 28 HCC, 7 hepatocellular adenoma (HA), 26 cirrotic nodules (CN) and 16 normal liver tissues (NLT) were immunostained for SDF-1 and CXCR4. SDF-1 and CXCR4 are detected in sinusoidal endothelial cells in HCC tissue, and their expressions are significantly higher than in non-HCC tissues. There was no significant correlation between SDF-1 expression and CXCR4 protein and the grade and stage of HCC. Overexpressions of SDF-1 and CXCR4 in sinusoidal endothelial cells in HCC suggest that the SDF-1/CXCR4 pathway plays a possible role in HCC progression through neoangiogenesis. Our data suggest that molecular strategies aimed at inhibiting the CXCR4/SDF-1 pathway might be of therapeutic use for the treatment of HCC.
    Journal of experimental & clinical cancer research: CR 01/2008; 26(4):527-33.
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    ABSTRACT: PCR analysis has been demonstrated as a valuable tool for detection of minimal residual disease (MRD) in lymphoid malignancies. However, the finding that patients with evidence of MRD sometimes remain in long-lasting remission directs further investigations toward biology of residual disease and/or quantification of MRD level. The study included 40 B-NHL patients--13/40 patients with high- (HG) and 27/40 with low-grade (LG) lymphoma. Seven patients achieved partial clinical remission (PR) and 33 patients achieved complete clinical remission (CCR) after chemotherapy. Peripheral blood samples were analyzed for MRD at up to ten follow-up points while samples of MRD+ patients and patients who achieved partial clinical response after therapy were further analyzed for the presence of t(14;18) and P53 and RAS genes mutations. The level of MRD was quantified in eight patients by PCR-limiting dilution method. Results: MRD was found in 13/33 patients (12 LG and 1 HG) who achieved CCR. The incidence of relapse was significantly higher in MRD+ vs. MRD- B-NHL patients (Fisher's exact test, p = 0.0083). In the LG group the incidence of relapse between MRD+ and MRD-patients was not significantly different. In the HG group MRD was detected in only one patient who subsequently relapsed. Significant difference in DFI between MRD+ and MRD- patients was not observed. Concerning MRD+ patients in CCR and patients who achieved PR, t(14;18) was found in six patients (4 relapsed). In the same group of patients P53, K- and N-RAS mutations were not found. H-RAS mutations were found in six patients--3 relapsed and 3 remain in CCR. The calculated number of IGH copies ranged from 4800 to 44,000. Our results demonstrated positive correlation between MRD-positivity and incidence of relapse in B-NHL patients, but could not indicate significance of P53 and RAS mutations for evaluation of residual clone malignancy. The study implies that MRD level, measured at one follow-up point, does not correlate with clinical outcome. The measurement of MRD level sequentially, at different follow-up points, seems to be a better parameter for the prediction of disease course.
    Journal of experimental & clinical cancer research: CR 01/2008; 26(4):535-42.
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    ABSTRACT: Insulin-secreting tumors are the commonest hormone-producing neoplasm of the gastrointestinal tract. They occur with an incidence of 4 cases per million per year. About 10% of them are metastatic and malignant insulinomas very rarely observed in children and in elderly. We report a rare case of very large malignant insulinoma in a 71-year-old woman admitted in our Oncological Institute on October 2005. She presented with fasting hypoglicemia (blood glucose 35 mg/dl) and high serum insulin levels (insulin 115.9 microU/ml). A computerized tomographic scan showed a pancreatic tail lesion of about 6 cm in max diameter and multiple liver metastases. A whole body scintiscan using 111In-DTPA-D-Phe1-octreotide was made and an increased uptake in the tail of the pancreas has been found. The patient was submitted to liver biopsy and the diagnosis of a metastatic insulin-secreting tumor was immunoistochemically confirmed. Due to the presence of some hypoglicemic episodes uncontrolled by medical treatment, on December 2005 the patient was admitted to surgical intervention with a body and tail pancreatic resection. Post-operatively the patient experienced again syncope with hypoglycemia and hyperinsulinemia. It was then decided to start a schedule of treatment with somatostatin analog (octreotide subcutaneously 500 microg three times a day) with a good control of blood glucose levels (101 mg/dl). A trans-arterial chemioembolization was planned but the patient died for pancreatic and cardiovascular complications before this treatment started.
    Journal of experimental & clinical cancer research: CR 01/2008; 26(4):603-7.
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    ABSTRACT: The purpose of this work is to introduce a new treatment approach and technique for partial breast irradiation in only one session to patients in prone position by using a dedicated positioning device. The patients were treated on a home-made treatment table top that allows the breast to hang down. A particular immobilization system was introduced in order to assure the reproducibility of patient positioning between the CT acquisition session and the treatment session. The clinical target volume (CTV) was outlined according to surgical clips position and/or tumor location on preoperative mammography. Because of negligible movement due to respiration, only an additional margin of 3 mm was added to obtain the planning target volume (PTV). Based on radiobiological calculations, a dose of 21 Gy was prescribed to PTV. The tumor bed was treated with 3D-CRT technique by using 5 fields and rotating the table while the gantry was approximately 90 or 270 degrees. Thirty patients were enrolled for this study chosen in conformity to an approved clinical protocol. The average percentage of PTV volume enclosed in the 90% and 95% of prescribed dose were 99.9 and 98.6% respectively, while only 3.4% of PTV volume received more than 105% of prescribed dose. Dose to 3% of skin volume was, on average, 15.2 Gy. In 97% of patients, less than 50% of the ipsilateral breast received a dose greater than half the prescribed dose. Mean doses to lungs, heart and contralateral breast were negligible. With a median follow-up of 9 months, no important early toxicity was observed both for skin and breast tissue. The treatment of breast tumor bed in prone position in only one session by using the 3D-CRT is technically feasible and seems to be a promising alternative to other accelerated partial breast irradiation techniques.
    Journal of experimental & clinical cancer research: CR 01/2008; 26(4):543-52.
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    ABSTRACT: This study was conducted to establish a feasible intraperitoneal xenograft model in nude mice which mimicked the dynamic progression of human ovarian cancer and to explore its potential for preclinical trials. A human ovarian tumor line SKOV3 was originally injected s.c. to develop tumors; then the tumors were harvested and minced into small particles for i.p. inoculation in three groups of nude mice which would be monitored consecutively. The intraperitoneal carcinomatosis and relevant organs were collected for histopathological dynamic comparison and CA125 immunohistochemical staining 7, 21 and 49 days after inoculation. An additional experiment with cisplatin sensitivity test was performed and tumor tissues were observed for apoptosis-Hoechst assay. The intraperitoneal carcinomatosis had a rapid progression which resulted in extensive dissemination on the peritoneal surfaces and invasion into abdominal lymph nodes, livers, pancreas and spleen. Tumor tissues revealed similar morphological features of primary tumor from which SKOV3 derived and part of in vivo tumor mass was positive for CA125. Cisplatin could significantly inhibit the intraperitoneal carcinomatosis growth. This model may provide a valuable platform to study the biological properties of ovarian cancer as well as to test new therapeutic strategies in preclinical trials.
    Journal of experimental & clinical cancer research: CR 01/2008; 26(4):467-74.
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    ABSTRACT: Cell cycle progression is mediated by a group of proteins named cyclins that activate a highly conserved family of protein kinases, the cyclin-dependent kinases (CDKs). CDKs are also regulated by related proteins called cdk inhibitors, grouped into two families: the INK4 inhibitors (p16, p15, p19 and p18) and the Cip/Kip inhibitors (p21, p27). Moreover, several tumour suppressor genes (such as Retinoblastoma gene and p53 gene) are implicated in the regulation of the molecular mechanism of cell division. Several studies report the importance of cell cycle regulator proteins in the pathogenesis and the prognosis of mesothelioma. This article will review the most recent data from the literature about the expression and the diagnostic and prognostic significance of cell cycle molecules in mesothelioma.
    Journal of experimental & clinical cancer research: CR 01/2008; 26(4):443-9.
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    ABSTRACT: When HCC is diagnosed at an early stage or liver is affected by a solitary metastasis they can be curable by surgical resection, but this may not be feasible when an extensive tumoural involvement is present. In these cases, possible non-surgical therapies include systemic chemotherapy, chemical ablation (ethanol or acetic acid), radiofrequency ablation, microwave ablation, cryotherapy and transarterial chemoembolisation. All the above mentioned treatments have advantages and disadvantages. In the present paper we reported our experience with selective internal radiation therapy (SIRT) of non-operable HCC and metastatic liver using 99Yttrium (99Y) radioactive microspheres, and our data are compared and discussed with those reported in the literature. A MEDLINE-based review of the literature has been made in the period between 1990 and April 2007. Detailed information on patients selection criteria, SIRT procedure, dose calculation, safety and adverse reactions, follow-up schedule, and clinical efficacy are provided. On the basis of our data, in agreement with those of the literature, SIRT has added another effective method for treatment of primary and secondary liver tumours, being successful in a large number of patients in different experiences. Moreover, SIRT is well tolerated and has minimal adverse effects. Despite being regarded as non-curative, it has been associated with improved survival, reduction in tumour marker, and regression in the number and size of lesions. Follow-up with imaging is essential to assess the response to therapy, and in this respect FDG PET has been shown to be more sensitive than CT, particularly in the early stages.
    Journal of experimental & clinical cancer research: CR 01/2008; 26(4):561-70.
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    ABSTRACT: The L-PAM-ILP procedures under true hyperthermal regime (41.5-41.8 degrees C) require both close control of the physical parameters of the treatment (temperatures profiles and time duration, artero-venous pressure, perfusate flow rate) and medical rationale (drug, dosage, fractioning, timing). All the above essential procedures must be supported by rigorous methodology, reliable operation of the medical devices and apparatus and real-time monitoring of the treatment parameters. Real-time monitoring is essential for proper trimming and modulation of the parameters during treatment. This paper delineates the technical improvements that we have implemented for drug leakage monitoring and control in the systemic circulation aimed at improving the therapeutic efficacy and at reducing the occurrence of unexpected complications.
    Journal of experimental & clinical cancer research: CR 01/2008; 26(4):433-42.
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    ABSTRACT: Blood vessels of tumors might carry specific markers that are usually related to angiogenesis. Investigating these heterogeneous molecules in different tumor vessels might be beneficial for promoting antiangiogenic therapy. In this study, in vivo screening of phage displayed peptide library was used to identify the peptides binding selectively to endothelial cells of human colon cancer. After four rounds of selection, one phage was obtained with a cyclic 7-mer peptide CPHSKPCLC homing to human colon adenocarcinoma. The results of ELISA and competitive inhibition assay clearly showed that the peptide bound specifically to the colon cancer xenograft in comparision with control organs, such as brain, heart, liver, spleen and kidney. This peptide was also identified to bind more heavily to human umbilical vein endothelial cells (HUVEC) than to gastric cancer cells, esophageal cancer cells, colon cancer cells and liver cancer cells. Immunohistochemical results showed that this phage peptide could bind to the endothelial cells of human colon cancer. The peptide might then be a potential candidate for targeted drug delivery in antivascular therapy and diagnosis of colon cancer.
    Journal of experimental & clinical cancer research: CR 01/2008; 26(4):509-14.
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    ABSTRACT: The incidence of hepatocellular carcinoma (HCC) is highest among primary liver cancer. HBV and HBV-induced liver cirrhosis may lead to HCC (1). At present, it is difficult to diagnose HCC at early stage or to differentiate HCC. Therefore, it is much needed to explore and develop a simple, rapid diagnostic method, which has higher sensitivity and specificity for HCC at early stage (2, 3). Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) is a novel non-electrophoresis-based proteomic technology. SELDI offers the advantages of rapid and simple examination as well as high specificity and sensitivity (4, 5). To our knowledge,there has been little study reported using SELDI-TOF-MS technology to investigate HCC. In this study, 25 cases of HCC patients not receiving any therapy, 25 cases receiving the interposition chemotherapy and 50 cases of the healthy people were tested by Weak cationic exchange (WCX2) protein chip and SELDI-TOF-MS. The differentially expressed peptides or proteins were analyzed by BioMarker Wizard software. At the different M/Z value range, seven peptides/ proteins were obviously different among these three groups. Four peptides including 6489.48Da, 6662.34Da, 8593.75Da and 8720.23Da were up-regulated in healthy controls, two including 7777.27Da and 9250.00Da were up-regulated in the patients with HCC without receiving any therapy and one protein of 16200.17Da was up-regulated in the patients with HCC receiving the interposition chemotherapy. Using Biomarker Pattern software, one pattern including two peptides (7777.27Da, 9250.00Da) can separate HCC without receiving any therapy from normal controls. This diagnosis pattern gave the much-improved sensitivity of 92% and the specificity of 100%. Through searching protein database, these seven peptides or proteins were identified as possible Galanin related peptide, Pro-neuregulin-4 protein, small inducible cytokine A15 precursor, 9 kDa protein, CSL-zincfinger protein 1, mitochondrial hinge protein, actin related protein, respectively. Using SELDI-TOF MS, the method of sieving the tumor markers from HCC becomes quick and valid. These differentially expressed peptides or proteins could be biomarkers of HCC in the serum and drug targets for treating HCC.
    Journal of experimental & clinical cancer research: CR 01/2008; 26(4):505-8.
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    ABSTRACT: DNA methylation is an important mechanism for gene silence. The purpose of this study was to investigate aberrant promoter methylation of the p16 and FHIT genes in tissues and plasma and loss of protein expression in esophageal precancerous conditions (EPC) and esophageal squamous cell carcinoma (ESCC) of high-risk area. Methylation-specific PCR(MSP) was employed to examine the DNA methylation in the plasma and tissues of 95 patients of EPC, ESCC and 10 chronic esophagitis (CE). Loss of protein expression of p16 and FHIT was detected immunohistochemically. In total 95 lesion tissues of EPC and ESCC, p16 methylation was found in 53 (55.79%) cases, and 41 of 53 (77.36%) cases were demonstrated deletion of the p16 protein immunohistochemically. FHIT methylation was found in 49 (51.58%) cases, and 40 of 49 (81.63%) were demonstrated deletion of the FHIT protein. Only 1 (10%) case of 10 CE p16 methylation was found in the tissues. In the plasma of total 105 samples, 2 of 23 high grade intraepithelial neoplasia (HGIN) and 12 of 37 ESCC were detected p16 methylation, and 2 of 23 HGIN and 14 of 37 ESCC were detected FHIT methylation. These results indicate that p16 and FHIT methylation may be one of the earliest events and an important mechanism for gene silencing in esophageal squamous cell carcinogenesis. This study may be helpful for screening the candidate molecular markers for early diagnosis of ESCC in high-risk area.
    Journal of experimental & clinical cancer research: CR 01/2008; 26(4):587-94.
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    ABSTRACT: This study was designed to evaluate the antitumor efficacy and feasibility of postoperative adjuvant metronomic chemotherapy using weekly low-dosage CPT-11 and UFT in colorectal cancer at high risk to recurrence. A total of 49 patients (24 stage IIIb and 25 distant metastasis) who underwent a R0 operation were enrolled in this prospective study. Forty mg/m2 of CPT-11 were administered on day 1, day 8, and on day 15 in 28-day cycles. A dosage of 335 mg/m2/day of UFT was given perorally on daily schedule. Cycles were repeated for 6 months, and were followed by UFT alone for further 6 months. One or more adverse effects were seen in 43 of the 49 patients. However, most of these effects were mild at grade 1 or 2: with only nausea in 3 patients, vomiting in 2, leucopenia in 2 and neutropenia in 2 at grade 3. The overall survival rates were favorable both in the stage IIIb group (5-year: 73%) and in the distant metastases group (5-year: 62%). Postoperative adjuvant metronomic chemotherapy using weekly low-dosage CPT-11 and UFT might be safe and feasible and prolong survival time in colorectal cancer at high risk to recurrence.
    Journal of experimental & clinical cancer research: CR 01/2008; 26(4):475-82.
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    ABSTRACT: Hypoxia occurs in most solid tumors as a result of inefficient vascular development and/or abnormal vascular architecture. During hypoxia, HIF-1alpha acts as the primary transcription factor functioning to activate multiple target genes, including vascular endothelial growth factor (VEGF). Several studies have demonstrated that in tumors HIF-1alpha mediates VEGF protein expression at the transcription level. We aimed to establish whether HCT116 colon cancer cell VEGF expression is regulated by HIF-1 levels after transient transfection with a GFP vector encoding the HIF-1alpha gene. HCT116 cell VEGF expression were therefore assayed by immunohistochemistry and ELISA. After transfection with phMGFP-HIF-1alpha, VEGF immunostaining was significantly increased in transfected cells as compared with untransfected HCT116 cells (p = 0.024, Student's t test); culture media VEGF levels assayed by ELISA were also significantly increased in transfected cells (p = 0.008, Student's t-test). These data suggest that HIF-1alpha may play an important role in colon cancer angiogenesis, both as a biomarker of metastatic potential and as a novel target for gene therapy.
    Journal of experimental & clinical cancer research: CR 01/2008; 26(4):515-9.
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    ABSTRACT: Lovastatin is one of a series of HMG-CoA reductase inhibitors used in the treatment of hypercholesterolemia. It may also inhibit atheroma formation by inhibiting the oxidation of low density lipoproteins (LDLs). We investigated the antioxidant properties of lovastatin and its effect on phagocyte-induced genotoxicity in mammalian cells. In a cytochrome c reduction assay using 106 phorbol ester-induced phagocytes as a positive control, lovastatin (10 microM) in its naturally occurring lactone form, had no effect. When converted to its acid form, however, superoxide anion formation was inhibted by 36%. Similarly, lovastatin in its acid form completely inhibited H2O2 formation by stimulated phagocytes. Using the fluorometric analysis of DNA unwinding, single-strand breakage was assayed in MRC-5 lung cells exposed to 106 human phagocytes +/- lovastatin (10 microM, 5 min. incubation). Stimulated phagocytes induced a decrease in double-stranded DNA to 48% of control values which, in the presence of lovastatin, reverted to 91% of control values. Lovastatin acts as an antioxidant by decreasing oxygen radical production by human phagocytes and may be important in abrogating the carcinogenic effect of chronic inflammation.
    Journal of experimental & clinical cancer research: CR 01/2008; 26(4):583-6.