Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results fr... more Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial. Lancet Oncol 2005; 6: 841-850. 7. Denham JW, Steigler A, Lamb DS et al. Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial. Lancet Oncol 2011; 12: 451-459. 8. D'Amico AV, Manola J, Loffredo M et al. 6-month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: a randomized controlled trial. JAMA 2004; 292: 821-827. 9. Lau WK, Blute ML, Bostwick DG et al. Prognostic factors for survival of patients with pathological Gleason score 7 prostate cancer: differences in outcome between primary Gleason grades 3 and 4.
adenoma-carcinoma sequence and samples were obtained from formalin-fixed and paraffin-embedded (F... more adenoma-carcinoma sequence and samples were obtained from formalin-fixed and paraffin-embedded (FFPE) normal colon and tumour tissues from a subset of patients (n = 21). Results Altered TRP concentrations were detected in plasma samples concomitant to pre-cancerous lesion and persisted during the adenoma-carcinoma transition. Moreover, the anatomical site of cancer lesions (colon or rectum) strongly influences the TRP metabolic profiles. Colon cancer patients exhibited increased TRP catabolism with respect to those affected by rectal cancer, suggesting that TRP's metabolism alterations play an important role in the onset and progression of colon cancer, but not in those of rectal cancer. Keywords Colorectal cancer • Biomarkers • Tryptophan • IDO • TPH ring. This step can be initiated either by indoleamine-2,3-dioxygenases 1 (IDO1), indoleamine-2,3-dioxygenases 2 (IDO2), or tryptophan-2,3-dioxygenase (TDO). Genes encoding IDO1 and IDO2 proteins are normally expressed in lung, brain, and placenta (Myint et al. 2007), whilst TDO is mainly expressed at hepatic level (Le Floc'h et al. 2011; van Baren and van den Eynde 2015). These enzymes are
3648 Background: The levels of telomere-specific reverse transcriptase (hTERT) transcripts have b... more 3648 Background: The levels of telomere-specific reverse transcriptase (hTERT) transcripts have been found to be a marker of colorectal cancer and tumor progression. Aim of the study was to investigate the role of plasma levels of total RNA and hTERT transcripts as marker of tumor response after preoperative chemoradiotherapy (pCRT) for rectal cancer. Methods: Pre- and post-pCRT plasma samples of 80 rectal cancer patients (median age, 62 years; male/female, 56/24) were available for the study. All patients received pCRT and, following the histopathology Dvorak tumor regression grade (TRG) classification, 45 of them were considered as non-responders (TRG 3-4-5) and 35 as responders (TRG 1-2). Quantification of RNA and hTERT transcripts (hTERT-AT) were performed by real time-PCR, using primer pair specific for HPRT and hTERT genes, respectively. Mann-Whitney Rank Sum Test was used to compare the levels of RNA and hTERT-AT between responders and non-responders at each time point. The Wilcoxon Signed Rank Tes...
Preoperative chemoradiotherapy (pCRT) followed by surgery is the standard treatment for locally a... more Preoperative chemoradiotherapy (pCRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC). However, tumor response to pCRT is not uniform, and there are no effective predictive methods. This study investigated whether specific gene and miRNA expression are associated with tumor response to pCRT. Tissue biopsies were obtained from patients before pCRT and resection. Gene and miRNA expression were analyzed using a one‐color microarray technique that compares signatures between responders (R) and non‐responders (NR), as measured based on tumor regression grade. Two groups composed of 38 “exploration cohort” and 21 “validation cohort” LARC patients were considered for a total of 32 NR and 27 R patients. In the first cohort, using SAM Two Class analysis, 256 genes and 29 miRNAs that were differentially expressed between the NR and R patients were identified. The anti‐correlation analysis showed that the same 8 miRNA interacted with different networks o...
Therapeutic management of Locally Advanced Rectal Cancer (LARC) involves pre-operative chemoradio... more Therapeutic management of Locally Advanced Rectal Cancer (LARC) involves pre-operative chemoradiotherapy (pCRT) followed by surgery. However, after pCRT the complete pathological response is approximately 20%, whereas in 20 to 40% of patients the response is poor or absent. Cancer biopsy specimens (n= 38) and serum samples (n= 34) obtained before pCRT from 38 LARC patients were included in the study. Patients were classified in responders (R, tumor regression grade [TRG] 1-2; n= 16) and non-responders (NR, TRG 3-5; n= 22) according to the pathological response observed upon surgery. We performed miRNA microarrays analysis on biopsy specimens, and validated the selected candidates both by qRT-PCR (tissue and serum) and by in situ hybridization (tissue, miR-125b) analyses. Eleven miRNAs were significantly different between R and NR (miR-154, miR-409-3p, miR-127-3p, miR-214*, miR-299-5p and miR-125b overexpressed in NR; miR-33a, miR-30e, miR-338-3p, miR-200a and miR-378 decreased). In ...
Early detection of colorectal cancer (CRC) remains a challenge. It has been highlighted that the ... more Early detection of colorectal cancer (CRC) remains a challenge. It has been highlighted that the pathological alterations within an organ and tissues might be reflected in serum or plasma proteomic/peptidic patterns. The aim of the study was to follow the changes in the plasma peptides associated to colorectal cancer progression by mass spectrometry. This study included 27 adenoma, 67 CRC (n = 33 I-II stage and n = 34 III-IV stage), 23 liver metastasis from CRC patients and 34 subjects disease-free as controls. For plasma peptides analysis, samples purification was performed on the Nanoporous Silica Chips technology followed by matrix-assisted laser desorption/ionisation-time of flight analysis. Since the high complexity of the obtained dataset, multivariate statistical analysis, and discriminant pattern recognition were performed for study groups classification. Forty-four of 88 ionic species were successfully identified as fragments of peptides and proteins physiologically circula...
Preoperative chemoradiotherapy is widely used to improve local control of disease, sphincter pres... more Preoperative chemoradiotherapy is widely used to improve local control of disease, sphincter preservation and to improve survival in patients with locally advanced rectal cancer. Patients enrolled in the present study underwent preoperative chemoradiotherapy, followed by surgical excision. Response to chemoradiotherapy was evaluated according to Mandard's Tumor Regression Grade (TRG). TRG 3, 4 and 5 were considered as partial or no response while TRG 1 and 2 as complete response. From pretherapeutic biopsies of 84 locally advanced rectal carcinomas available for the analysis, only 42 of them showed 70% cancer cellularity at least. By determining gene expression profiles, responders and non-responders showed significantly different expression levels for 19 genes (P <0.001). We fitted a logistic model selected with a stepwise procedure optimizing the Akaike Information Criterion (AIC) and then validated by means of leave one out cross validation (LOOCV, accuracy=95%). Four gene...
MiR-182 expression was evaluated by qRT-PCR and in situ hybridization in 20 tubular adenomas, 50 ... more MiR-182 expression was evaluated by qRT-PCR and in situ hybridization in 20 tubular adenomas, 50 colorectal carcinoma (CRC), and 40 CRC liver metastases. Control samples obtained from patients with irritable bowel syndrome, or tumor-matched normal colon mucosa were analyzed (n=50). MiR-182 expression increased progressively and significantly along with the colorectal carcinogenesis cascade, and in CRC liver metastases. The inverse relation between miR-182 and the expression of its target gene ENTPD5 was investigated by immunohistochemical analysis. We observed that normal colocytes featured a strong ENTPD5 cytoplasmic expression whereas a significantly and progressively lower expression was present along with dedifferentiation of the histologic phenotype. Plasma samples from 51 CRC patients and controls were tested for miR-182 expression. Plasma miR-182 concentrations were significantly higher in CRC patients than in healthy controls or patients with colon polyps at endoscopy. Moreo...
Clinical cancer research : an official journal of the American Association for Cancer Research, 1998
The activation of zymogen and the amount of proteinase and its inhibition are important in determ... more The activation of zymogen and the amount of proteinase and its inhibition are important in determining the eventual activity of matrix-degrading enzymes involved in tumor aggressiveness. To evaluate a gene complement leading to matrix metalloproteinase 2 (MMP-2; Mr 72,000 gelatinase) activity, membrane type 1 MMP (MT1-MMP), urokinase-type plasminogen activator, MMP-2, and tissue inhibitor of metalloproteinase 2 transcriptional levels were measured in gastric carcinoma biopsies. Comparative tumor:normal tissue reverse transcription-PCR in a cohort of 25 patients revealed up to a 10-fold difference in the expression of MT1-MMP, a metalloproteinase that has been proposed as a membrane receptor activator of MMP-2; a 1-unit increment resulted in a 30% risk to survival. A 20% risk also resulted from a 1-unit increment in the MT1-MMP: MMP-2 ratio, which showed differences of up to 15-fold. Instead, the expression of urokinase-type plasminogen activator, which trips off a cascade ending in ...
Locally advanced rectal cancer is currently treated with pre-operative radiochemotherapy (pRCT), ... more Locally advanced rectal cancer is currently treated with pre-operative radiochemotherapy (pRCT), but the response is not uniform. Identification of patients with higher likelihood of responding to pRCT is clinically relevant, as patients with resistant tumors could be spared exposure to radiation or DNA-damaging drugs that are associated with adverse side effects. To highlight predictive biomarkers of response to pRCT, a systematic search of PubMed was conducted with a combination of the following terms: "rectal", "predictive", "radiochemotherapy", "neoadjuvant", "response" and "biomarkers". Genetic polymorphisms in epithelial growth factor receptor (EGFR) and thymidylate synthase (TS) genes, the expression of several markers, such as EGFR, bcl-2/bax and cyclooxygenase (COX)-2, and circulating biomarkers, such as serum carcinoembryonic antigen (CEA) level, are promising as predictor markers, but need to be further evaluated. The majority of the studies did not support the predictive value of p53, while the values of Ki-67, TS and p21 is still controversial. Gene expression profiles of thousands of genes using microarrays, microRNA studies and the search for new circulating molecules, such as human telomerase reverse transcriptase mRNA and cell-free DNA, are providing
Data on genetic susceptibility to sporadic gastric carcinoma have been published at a growing pac... more Data on genetic susceptibility to sporadic gastric carcinoma have been published at a growing pace, but to date no comprehensive overview and quantitative summary has been available. We conducted a systematic review and meta-analysis of the evidence on the association between DNA variation and risk of developing stomach cancer. To assess result credibility, summary evidence was graded according to the Venice criteria and false positive report probability (FPRP) was calculated to further validate result noteworthiness. Meta-analysis was also conducted for subgroups, which were defined by ethnicity (Asian vs Caucasian), tumour histology (intestinal vs diffuse), tumour site (cardia vs non-cardia) and Helicobacter pylori infection status (positive vs negative). Literature search identified 824 eligible studies comprising 2 530 706 subjects (cases: 261 386 (10.3%)) and investigating 2841 polymorphisms involving 952 distinct genes. Overall, we performed 456 primary and subgroup meta-analy...
Background The detection of circulating tumor cells (CTC) is considered a promising tool for impr... more Background The detection of circulating tumor cells (CTC) is considered a promising tool for improving risk stratification in patients with solid tumors. We investigated on whether the expression of CTC related genes adds any prognostic power to the TNM staging system in patients with gastric carcinoma. Methods Seventy patients with TNM stage I to IV gastric carcinoma were retrospectively enrolled. Peripheral blood samples were tested by means of quantitative real time PCR (qrtPCR) for the expression of four CTC related genes: carcinoembryonic antigen (CEA), cytokeratin-19 (CK19), vascular endothelial growth factor (VEGF) and Survivin (BIRC5). Results Gene expression of Survivin, CK19, CEA and VEGF was higher than in normal controls in 98.6%, 97.1%, 42.9% and 38.6% of cases, respectively, suggesting a potential diagnostic value of both Survivin and CK19. At multivariable survival analysis, TNM staging and Survivin mRNA levels were retained as independent prognostic factors, demonstr...
Detection of circulating tumor cells (CTCs) might improve current staging procedures by identifyi... more Detection of circulating tumor cells (CTCs) might improve current staging procedures by identifying a subgroup of patients with minimal residual disease and thus a higher risk of disease recurrence. Forty patients with ≥2‐mm‐thick cutaneous melanoma with or without lymph node metastasis were enrolled. After standard radical surgery and adjuvant therapy in case of lymph node metastasis, patients were followed up with routine physical and radiologic assessments as well as serial PCR‐based analysis of CTCs using 2 melanoma markers (tyrosinase and Melan‐A/Mart‐1). After a median follow‐up of 30 months, 18 patients had disease recurrence and 28 were PCR‐positive before the disease became clinically evident. The sensitivity of the molecular test was 83%. Median time to PCR positivity and median PCR‐to‐relapse time were 12 and 8 months, respectively. At multivariate analysis, PCR positivity was an independent predictor of disease recurrence (hazard ratio = 2.06, 95% CI 1.07–3.35; p = 0.03)...
Marioni G, Agostini M, Bedin C, Blandamura S, Stellini E, Favero G, Lionello M, Giacomelli L, Bur... more Marioni G, Agostini M, Bedin C, Blandamura S, Stellini E, Favero G, Lionello M, Giacomelli L, Burti S, D’Angelo E, Nitti D, Staffieri A & De Filippis C (2012) Histopathology 61, 247–256Survivin and laryngeal carcinoma prognosis: nuclear localization and expression of splice variantsAims: Aberrant survivin expression in cancer cells has been associated with tumour progression, radiation/drug resistance and shorter patient survival. The aim of the present study was to investigate survivin expression in laryngeal carcinoma (LSCC) tissue and – for the first time at this site – the expression of survivin splice variants. P53 was also studied.Methods and results: Survivin and p53 expression was determined immunohistochemically in 86 consecutive patients operated for LSCC. Survivin mRNA expression was assessed by quantitative real‐time polymerase chain reaction (PCR). Hot‐spot mutations in exons 5, 6, 7 and 8 of the TP53 gene were studied by sequencing analysis. A nuclear localization f...
Introduction 3. TNF anticancer activities 3.1. TNF direct cytotoxicity 3.2. TNF as a tumor vascul... more Introduction 3. TNF anticancer activities 3.1. TNF direct cytotoxicity 3.2. TNF as a tumor vasculature disrupting agent 3.3. TNF synergism with chemotherapeutic drugs 3.4. TNF and antitumor immunity 4. Tumor promoting effects of TNF 4.1. TNF and cancer development 4.2. TNF and cancer progression 4.3. TNF gene polymorphisms 5. Perspective 6. Acknowledgements 7. References
European Journal of Vascular and Endovascular Surgery, 2002
Objective and design: high plasma levels of Interleukin-6 (IL-6) are found in patients with ather... more Objective and design: high plasma levels of Interleukin-6 (IL-6) are found in patients with atherosclerotic disorders. Recently, a common polymorphism of the IL-6 gene promoter, influencing the transcription rate of the gene, has been described and associated with atherosclerosis of carotid and coronary arteries. The objective of this study was to test whether IL-6 gene promoter polymorphism is associated with peripheral artery occlusive disease (PAOD) in a case-control study. Methods: IL-6 gene promoter polymorphism was evaluated by polymerase chain reaction followed by restriction enzyme analysis in 84 patients affected by PAOD and 183 controls. Results: the distribution of IL-6 genotypes was: patients with PAOD: 44 GG, 30 GC, 10 CC; control subjects: 53 GG, 80 GC, 50 CC. The GG genotype was significantly more common in the PAOD group (p 5 0.0001), while the CC genotype was significantly more common in control patients (p 0.005). Conclusions: this study indicates a strong association between IL-6 gene polymorphism and PAOD and support the hypothesis that IL-6 and IL-6 gene polymorphism are important in the pathophysiology and evolution of ischaemic diseases of the lower limbs.
Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results fr... more Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial. Lancet Oncol 2005; 6: 841-850. 7. Denham JW, Steigler A, Lamb DS et al. Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial. Lancet Oncol 2011; 12: 451-459. 8. D'Amico AV, Manola J, Loffredo M et al. 6-month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: a randomized controlled trial. JAMA 2004; 292: 821-827. 9. Lau WK, Blute ML, Bostwick DG et al. Prognostic factors for survival of patients with pathological Gleason score 7 prostate cancer: differences in outcome between primary Gleason grades 3 and 4.
adenoma-carcinoma sequence and samples were obtained from formalin-fixed and paraffin-embedded (F... more adenoma-carcinoma sequence and samples were obtained from formalin-fixed and paraffin-embedded (FFPE) normal colon and tumour tissues from a subset of patients (n = 21). Results Altered TRP concentrations were detected in plasma samples concomitant to pre-cancerous lesion and persisted during the adenoma-carcinoma transition. Moreover, the anatomical site of cancer lesions (colon or rectum) strongly influences the TRP metabolic profiles. Colon cancer patients exhibited increased TRP catabolism with respect to those affected by rectal cancer, suggesting that TRP's metabolism alterations play an important role in the onset and progression of colon cancer, but not in those of rectal cancer. Keywords Colorectal cancer • Biomarkers • Tryptophan • IDO • TPH ring. This step can be initiated either by indoleamine-2,3-dioxygenases 1 (IDO1), indoleamine-2,3-dioxygenases 2 (IDO2), or tryptophan-2,3-dioxygenase (TDO). Genes encoding IDO1 and IDO2 proteins are normally expressed in lung, brain, and placenta (Myint et al. 2007), whilst TDO is mainly expressed at hepatic level (Le Floc'h et al. 2011; van Baren and van den Eynde 2015). These enzymes are
3648 Background: The levels of telomere-specific reverse transcriptase (hTERT) transcripts have b... more 3648 Background: The levels of telomere-specific reverse transcriptase (hTERT) transcripts have been found to be a marker of colorectal cancer and tumor progression. Aim of the study was to investigate the role of plasma levels of total RNA and hTERT transcripts as marker of tumor response after preoperative chemoradiotherapy (pCRT) for rectal cancer. Methods: Pre- and post-pCRT plasma samples of 80 rectal cancer patients (median age, 62 years; male/female, 56/24) were available for the study. All patients received pCRT and, following the histopathology Dvorak tumor regression grade (TRG) classification, 45 of them were considered as non-responders (TRG 3-4-5) and 35 as responders (TRG 1-2). Quantification of RNA and hTERT transcripts (hTERT-AT) were performed by real time-PCR, using primer pair specific for HPRT and hTERT genes, respectively. Mann-Whitney Rank Sum Test was used to compare the levels of RNA and hTERT-AT between responders and non-responders at each time point. The Wilcoxon Signed Rank Tes...
Preoperative chemoradiotherapy (pCRT) followed by surgery is the standard treatment for locally a... more Preoperative chemoradiotherapy (pCRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC). However, tumor response to pCRT is not uniform, and there are no effective predictive methods. This study investigated whether specific gene and miRNA expression are associated with tumor response to pCRT. Tissue biopsies were obtained from patients before pCRT and resection. Gene and miRNA expression were analyzed using a one‐color microarray technique that compares signatures between responders (R) and non‐responders (NR), as measured based on tumor regression grade. Two groups composed of 38 “exploration cohort” and 21 “validation cohort” LARC patients were considered for a total of 32 NR and 27 R patients. In the first cohort, using SAM Two Class analysis, 256 genes and 29 miRNAs that were differentially expressed between the NR and R patients were identified. The anti‐correlation analysis showed that the same 8 miRNA interacted with different networks o...
Therapeutic management of Locally Advanced Rectal Cancer (LARC) involves pre-operative chemoradio... more Therapeutic management of Locally Advanced Rectal Cancer (LARC) involves pre-operative chemoradiotherapy (pCRT) followed by surgery. However, after pCRT the complete pathological response is approximately 20%, whereas in 20 to 40% of patients the response is poor or absent. Cancer biopsy specimens (n= 38) and serum samples (n= 34) obtained before pCRT from 38 LARC patients were included in the study. Patients were classified in responders (R, tumor regression grade [TRG] 1-2; n= 16) and non-responders (NR, TRG 3-5; n= 22) according to the pathological response observed upon surgery. We performed miRNA microarrays analysis on biopsy specimens, and validated the selected candidates both by qRT-PCR (tissue and serum) and by in situ hybridization (tissue, miR-125b) analyses. Eleven miRNAs were significantly different between R and NR (miR-154, miR-409-3p, miR-127-3p, miR-214*, miR-299-5p and miR-125b overexpressed in NR; miR-33a, miR-30e, miR-338-3p, miR-200a and miR-378 decreased). In ...
Early detection of colorectal cancer (CRC) remains a challenge. It has been highlighted that the ... more Early detection of colorectal cancer (CRC) remains a challenge. It has been highlighted that the pathological alterations within an organ and tissues might be reflected in serum or plasma proteomic/peptidic patterns. The aim of the study was to follow the changes in the plasma peptides associated to colorectal cancer progression by mass spectrometry. This study included 27 adenoma, 67 CRC (n = 33 I-II stage and n = 34 III-IV stage), 23 liver metastasis from CRC patients and 34 subjects disease-free as controls. For plasma peptides analysis, samples purification was performed on the Nanoporous Silica Chips technology followed by matrix-assisted laser desorption/ionisation-time of flight analysis. Since the high complexity of the obtained dataset, multivariate statistical analysis, and discriminant pattern recognition were performed for study groups classification. Forty-four of 88 ionic species were successfully identified as fragments of peptides and proteins physiologically circula...
Preoperative chemoradiotherapy is widely used to improve local control of disease, sphincter pres... more Preoperative chemoradiotherapy is widely used to improve local control of disease, sphincter preservation and to improve survival in patients with locally advanced rectal cancer. Patients enrolled in the present study underwent preoperative chemoradiotherapy, followed by surgical excision. Response to chemoradiotherapy was evaluated according to Mandard's Tumor Regression Grade (TRG). TRG 3, 4 and 5 were considered as partial or no response while TRG 1 and 2 as complete response. From pretherapeutic biopsies of 84 locally advanced rectal carcinomas available for the analysis, only 42 of them showed 70% cancer cellularity at least. By determining gene expression profiles, responders and non-responders showed significantly different expression levels for 19 genes (P <0.001). We fitted a logistic model selected with a stepwise procedure optimizing the Akaike Information Criterion (AIC) and then validated by means of leave one out cross validation (LOOCV, accuracy=95%). Four gene...
MiR-182 expression was evaluated by qRT-PCR and in situ hybridization in 20 tubular adenomas, 50 ... more MiR-182 expression was evaluated by qRT-PCR and in situ hybridization in 20 tubular adenomas, 50 colorectal carcinoma (CRC), and 40 CRC liver metastases. Control samples obtained from patients with irritable bowel syndrome, or tumor-matched normal colon mucosa were analyzed (n=50). MiR-182 expression increased progressively and significantly along with the colorectal carcinogenesis cascade, and in CRC liver metastases. The inverse relation between miR-182 and the expression of its target gene ENTPD5 was investigated by immunohistochemical analysis. We observed that normal colocytes featured a strong ENTPD5 cytoplasmic expression whereas a significantly and progressively lower expression was present along with dedifferentiation of the histologic phenotype. Plasma samples from 51 CRC patients and controls were tested for miR-182 expression. Plasma miR-182 concentrations were significantly higher in CRC patients than in healthy controls or patients with colon polyps at endoscopy. Moreo...
Clinical cancer research : an official journal of the American Association for Cancer Research, 1998
The activation of zymogen and the amount of proteinase and its inhibition are important in determ... more The activation of zymogen and the amount of proteinase and its inhibition are important in determining the eventual activity of matrix-degrading enzymes involved in tumor aggressiveness. To evaluate a gene complement leading to matrix metalloproteinase 2 (MMP-2; Mr 72,000 gelatinase) activity, membrane type 1 MMP (MT1-MMP), urokinase-type plasminogen activator, MMP-2, and tissue inhibitor of metalloproteinase 2 transcriptional levels were measured in gastric carcinoma biopsies. Comparative tumor:normal tissue reverse transcription-PCR in a cohort of 25 patients revealed up to a 10-fold difference in the expression of MT1-MMP, a metalloproteinase that has been proposed as a membrane receptor activator of MMP-2; a 1-unit increment resulted in a 30% risk to survival. A 20% risk also resulted from a 1-unit increment in the MT1-MMP: MMP-2 ratio, which showed differences of up to 15-fold. Instead, the expression of urokinase-type plasminogen activator, which trips off a cascade ending in ...
Locally advanced rectal cancer is currently treated with pre-operative radiochemotherapy (pRCT), ... more Locally advanced rectal cancer is currently treated with pre-operative radiochemotherapy (pRCT), but the response is not uniform. Identification of patients with higher likelihood of responding to pRCT is clinically relevant, as patients with resistant tumors could be spared exposure to radiation or DNA-damaging drugs that are associated with adverse side effects. To highlight predictive biomarkers of response to pRCT, a systematic search of PubMed was conducted with a combination of the following terms: "rectal", "predictive", "radiochemotherapy", "neoadjuvant", "response" and "biomarkers". Genetic polymorphisms in epithelial growth factor receptor (EGFR) and thymidylate synthase (TS) genes, the expression of several markers, such as EGFR, bcl-2/bax and cyclooxygenase (COX)-2, and circulating biomarkers, such as serum carcinoembryonic antigen (CEA) level, are promising as predictor markers, but need to be further evaluated. The majority of the studies did not support the predictive value of p53, while the values of Ki-67, TS and p21 is still controversial. Gene expression profiles of thousands of genes using microarrays, microRNA studies and the search for new circulating molecules, such as human telomerase reverse transcriptase mRNA and cell-free DNA, are providing
Data on genetic susceptibility to sporadic gastric carcinoma have been published at a growing pac... more Data on genetic susceptibility to sporadic gastric carcinoma have been published at a growing pace, but to date no comprehensive overview and quantitative summary has been available. We conducted a systematic review and meta-analysis of the evidence on the association between DNA variation and risk of developing stomach cancer. To assess result credibility, summary evidence was graded according to the Venice criteria and false positive report probability (FPRP) was calculated to further validate result noteworthiness. Meta-analysis was also conducted for subgroups, which were defined by ethnicity (Asian vs Caucasian), tumour histology (intestinal vs diffuse), tumour site (cardia vs non-cardia) and Helicobacter pylori infection status (positive vs negative). Literature search identified 824 eligible studies comprising 2 530 706 subjects (cases: 261 386 (10.3%)) and investigating 2841 polymorphisms involving 952 distinct genes. Overall, we performed 456 primary and subgroup meta-analy...
Background The detection of circulating tumor cells (CTC) is considered a promising tool for impr... more Background The detection of circulating tumor cells (CTC) is considered a promising tool for improving risk stratification in patients with solid tumors. We investigated on whether the expression of CTC related genes adds any prognostic power to the TNM staging system in patients with gastric carcinoma. Methods Seventy patients with TNM stage I to IV gastric carcinoma were retrospectively enrolled. Peripheral blood samples were tested by means of quantitative real time PCR (qrtPCR) for the expression of four CTC related genes: carcinoembryonic antigen (CEA), cytokeratin-19 (CK19), vascular endothelial growth factor (VEGF) and Survivin (BIRC5). Results Gene expression of Survivin, CK19, CEA and VEGF was higher than in normal controls in 98.6%, 97.1%, 42.9% and 38.6% of cases, respectively, suggesting a potential diagnostic value of both Survivin and CK19. At multivariable survival analysis, TNM staging and Survivin mRNA levels were retained as independent prognostic factors, demonstr...
Detection of circulating tumor cells (CTCs) might improve current staging procedures by identifyi... more Detection of circulating tumor cells (CTCs) might improve current staging procedures by identifying a subgroup of patients with minimal residual disease and thus a higher risk of disease recurrence. Forty patients with ≥2‐mm‐thick cutaneous melanoma with or without lymph node metastasis were enrolled. After standard radical surgery and adjuvant therapy in case of lymph node metastasis, patients were followed up with routine physical and radiologic assessments as well as serial PCR‐based analysis of CTCs using 2 melanoma markers (tyrosinase and Melan‐A/Mart‐1). After a median follow‐up of 30 months, 18 patients had disease recurrence and 28 were PCR‐positive before the disease became clinically evident. The sensitivity of the molecular test was 83%. Median time to PCR positivity and median PCR‐to‐relapse time were 12 and 8 months, respectively. At multivariate analysis, PCR positivity was an independent predictor of disease recurrence (hazard ratio = 2.06, 95% CI 1.07–3.35; p = 0.03)...
Marioni G, Agostini M, Bedin C, Blandamura S, Stellini E, Favero G, Lionello M, Giacomelli L, Bur... more Marioni G, Agostini M, Bedin C, Blandamura S, Stellini E, Favero G, Lionello M, Giacomelli L, Burti S, D’Angelo E, Nitti D, Staffieri A & De Filippis C (2012) Histopathology 61, 247–256Survivin and laryngeal carcinoma prognosis: nuclear localization and expression of splice variantsAims: Aberrant survivin expression in cancer cells has been associated with tumour progression, radiation/drug resistance and shorter patient survival. The aim of the present study was to investigate survivin expression in laryngeal carcinoma (LSCC) tissue and – for the first time at this site – the expression of survivin splice variants. P53 was also studied.Methods and results: Survivin and p53 expression was determined immunohistochemically in 86 consecutive patients operated for LSCC. Survivin mRNA expression was assessed by quantitative real‐time polymerase chain reaction (PCR). Hot‐spot mutations in exons 5, 6, 7 and 8 of the TP53 gene were studied by sequencing analysis. A nuclear localization f...
Introduction 3. TNF anticancer activities 3.1. TNF direct cytotoxicity 3.2. TNF as a tumor vascul... more Introduction 3. TNF anticancer activities 3.1. TNF direct cytotoxicity 3.2. TNF as a tumor vasculature disrupting agent 3.3. TNF synergism with chemotherapeutic drugs 3.4. TNF and antitumor immunity 4. Tumor promoting effects of TNF 4.1. TNF and cancer development 4.2. TNF and cancer progression 4.3. TNF gene polymorphisms 5. Perspective 6. Acknowledgements 7. References
European Journal of Vascular and Endovascular Surgery, 2002
Objective and design: high plasma levels of Interleukin-6 (IL-6) are found in patients with ather... more Objective and design: high plasma levels of Interleukin-6 (IL-6) are found in patients with atherosclerotic disorders. Recently, a common polymorphism of the IL-6 gene promoter, influencing the transcription rate of the gene, has been described and associated with atherosclerosis of carotid and coronary arteries. The objective of this study was to test whether IL-6 gene promoter polymorphism is associated with peripheral artery occlusive disease (PAOD) in a case-control study. Methods: IL-6 gene promoter polymorphism was evaluated by polymerase chain reaction followed by restriction enzyme analysis in 84 patients affected by PAOD and 183 controls. Results: the distribution of IL-6 genotypes was: patients with PAOD: 44 GG, 30 GC, 10 CC; control subjects: 53 GG, 80 GC, 50 CC. The GG genotype was significantly more common in the PAOD group (p 5 0.0001), while the CC genotype was significantly more common in control patients (p 0.005). Conclusions: this study indicates a strong association between IL-6 gene polymorphism and PAOD and support the hypothesis that IL-6 and IL-6 gene polymorphism are important in the pathophysiology and evolution of ischaemic diseases of the lower limbs.
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Papers by Donato Nitti