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: 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: 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: 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: Sporadic colorectal cancer (SCRC) occurring in young patients represent a subset with a higher proportion of advanced tumors and a poor prognosis, however, the genetic basis of SCRCs has not yet been sufficiently studied. We assigned 16 SCRC patients aged 40 years or less to group 1, and 30 SCRCs patients aged 65 years or more to group 2. The methylation status in the promoter of 7 tumor suppressor genes regarding these two groups was then examined. The average number of hypermethylated tumor-related genes per sample in group 1 was 1.50 +/- 0.07, which was significantly lower than that in group 2 of 2.73 +/- 1.24 (p = 0.0040). The frequencies of the promoter hypermethylation of hMLH1, p15INK4b, p16INK4a, and RASSF1A in group 1 were 12.5%, 12.5%, 12.5%, 6.3%, and 0.0%, which were substantially less frequent than those same rates observed in group 2. In contrast, the frequencies of the promoter hypermethylation of APC, MGMT, p14ARF, in group 1 were 43.8%, 37.5%, and 31.3%, which were as frequent as those seen in group 2. The promoter hypermethylation of APC, MGMT, and pl4ARF is therefore considered to be closely related to the development of SCRCs in young patients, regardless of aging.
    Journal of experimental & clinical cancer research: CR 01/2008; 26(4):521-6.
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    ABSTRACT: Metastases to the bones of the hands and feet (acrometastases) represent an uncommon site of recurrence of renal cell carcinoma (RCC). Although challenging, the prompt recognition of solitary acrometastasis from RCC is of crucial importance, since surgical resection of the acrometastasis in the absence of active systemic disease has been reported as beneficial for a subgroup of patients with RCC. Here, we report the case of a patient with RCC metastatic to the left index finger treated with surgical resection of the acrometastasis who shortly thereafter developed progressive disease despite such an aggressive surgical approach.
    Journal of experimental & clinical cancer research: CR 01/2008; 26(4):595-7.
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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: 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: 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: 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: 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: 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: 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.
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    ABSTRACT: More than the normal physiological concentration of superoxide anion radicals in and around the cell may significantly and quite often adversely modify the structure of several crucial biomolecules like DNA, proteins, and lipids that may lead to cytotoxicity and/or disease development. In this study, we generated superoxide anion radical in vitro from riboflavin under cool white fluorescent light of 800 Lux. The radical formation was confirmed by its quenching with superoxide dismutase enzyme and reduction of nitrobluetetrazolium dye. Double stranded DNA exposed to superoxide anion radical showed hyperchromicity, single strand breaks, decrease in melting temperature, and modification of thymine, adenine and guanine bases. The superoxide-modified DNA was used as antigen to detect modified-DNA reactive antibodies by immunoassay in sera of patients diagnosed for cancer of breast, lung, liver, urinary bladder and gall bladder. In competition ELISA using superoxide-modified DNA and control DNA as inhibitors, serum antibodies from cancer patients were found to recognize superoxide modified-DNA better than control DNA under identical conditions. The results of the study are significant because autoantibodies are being recognized with increasing frequency in cancer and humoral immunity is emerging as a prominent response in many different types of cancer.
    Journal of experimental & clinical cancer research: CR 01/2008; 26(4):499-504.
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    ABSTRACT: The HPV genotype concordance in the sexual couples could support the sexual viral transmission of HPV infection. The present study contains a case-report of a stable Italian sex couple harbouring the same five HPV genotypes in their genital samples. The female partner, affected by vulvar condilomatosis, evidenced positivity in her cervicovaginal scraping with high risk HPV DNA Hybrid Capture 2 test and was negative at liquid-based performed Pap Test and at colposcopic examination. The male partner was clinically healthy regarding his external genitalia. In both male and female genital scrapings, the following HPV genotypes were detected by means of a PCR-based assay: 6, 16, 53, 73 and 84. This considerably high genotype concordance does not appear to be casual and supports, in our opinion, the hypothesis that genital HPV types are sexually transmitted agents
    Journal of experimental & clinical cancer research: CR 01/2008; 26(4):609-12.