Angiogenesis is important in the growth and progression of solid tumours. The main pro-angiogenic factor, namely vascular endothelial growth factor (VEGF), also known as vascular permeability factor, ...is a potent angiogenic cytokine that induces mitosis and also regulates the permeability of endothelial cells. The soluble isoform of VEGF is a dimeric glycoprotein of 36-46 kDa, induced by hypoxia and oncogenic mutation and it binds to two specific tyrosinekinase receptors: VEGF-1 (flt-1) and VEGF-2 (KDR/flk1). An increase in VEGF expression in tumour tissue or some blood compartments (i.e. serum or plasma) has been found in solid and haematological malignancies of various origins and is associated with metastasis formation and poor prognosis. Bevacizumab, a recombinant humanised monoclonal antibody developed against VEGF, binds to soluble VEGF, preventing receptor binding and inhibiting endothelial cell proliferation and vessel formation. Pre-clinical and clinical studies have shown that bevacizumab alone or in combination with a cytotoxic agent decreases tumour growth and increases median survival time and time to tumour progression. Bevacizumab is the first anti-angiogenetic treatment approved by the American Food and Drug Administration in the first-line treatment of metastatic colorectal cancer. It has shown preliminary evidence of efficacy for breast, non-small-cell lung, pancreatic, prostate, head and neck and renal cancer as well as haematological malignancies. Common toxicities associated with bevacizumab include hypertension, proteinuria, bleeding episodes and thrombotic events. This review summarises the critical role of VEGF and discusses the data available on bevacizumab, from the humanisation of its parent murine monoclonal antibody (mAb) A.4.6.1 to its use in cancer clinical trials.
Tryptase is a serin protease stored and released from mast cells (MCs) that plays a role in tumour angiogenesis. In this study we aimed to evaluate serum tryptase levels in colo-rectal cancer (CRC) ...patients before (STLBS) and after (STLAS) radical surgical resection. We also evaluated mast cell density positive to tryptase (MCDPT) and microvascular density (MVD) in primary tumour tissue.
A series of 61 patients with stage B and C CRC (according to the Astler and Coller staging system) were selected. Serum blood samples were collected from patients one day before and one day after surgery. Tryptase levels were measured using the UniCAP Tryptase Fluoroenzymeimmunoassay (Pharmacia, Uppsala, Sweden). Tumour sections were immunostained with a primary anti-tryptase antibody (clone AA1; Dako, Glostrup, Denmark) and an anti CD-34 antibody (QB-END 10; Bio-Optica Milan, Italy) by means of immunohistochemistry and then evaluated by image analysis methods.
The mean ± s.d. STLBS and STLAS was 5.63±2.61 µg/L, and 3.39±1.47 µg/L respectively and a significant difference between mean levels was found: p = 0.000 by t-test. The mean ± s.d. of MCDPT and MVD was 8.13±3.28 and 29.16±7.39 respectively. A strong correlation between STLBS and MVD (r = 0.83, p = 0.000); STLBS and MCDPT (r = 0.60, p = 0.003); and MCDPT and MVD (r = 0.73; p = 0.001) was found.
Results demonstrated higher STLBS in CRC patients, indicating an involvement of MC tryptase in CRC angiogenesis. Data also indicated lower STLAS, suggesting the release of tryptase from tumour-infiltrating MCs. Serum tryptase levels may therefore play a role as a novel bio-marker predictive of response to radical surgery. In this context tryptase inhibitors such as Gabexate and Nafamostat Mesilate might be evaluated in adjuvant clinical trials as a new anti-angiogenic approach.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Colorectal cancer (CRC) is the most common tumor of the gastrointestinal tract. Anastomotic leak (AL) and prolonged postoperative ileus (PPOI) are two important complications of colorectal surgery. ...In this observational retrospective study, we evaluated the positive effects of transanal tube No Coil® in patients with CRC undergoing low anterior resection (LAR) and left hemicolectomy (LC).
Thirty-eight cases and forty controls resulted eligible for the final sample. No Coil® placement (SapiMed Spa, Alessandria, Italy) was considered an inclusion criteria for the case group. No Coil® was placed immediately after the end of surgical treatment.
PPOI was significantly more frequent in the control group. AL was evident in 1 patient (2.6%) of cases and 3 patients (7.5%) of controls. No statistical difference was found in AL occurrence between groups. POI days and AL resulted associated with hospital stay. POI days were negatively associated with No Coil placement and positively with AL.
With our preliminary data, we suggest that No Coil® placement can be considered as a valuable procedure assisting colorectal surgery, but further studies are required to confirm and enlarge actual evidence.
Colorectal cancer (CRC) is considered one of the most frequent neoplasms of the digestive tract with a high mortality rate. Left hemicolectomy (LC) and low anterior resection (LAR) with minimally ...invasive laparoscopic and robotic approaches or with the open technique are the gold standard curative treatment.
Seventy-seven patients diagnosed with CRC were recruited between September 2017 and September 2021. All patients underwent a preoperative staging with a full-body CT scan. The goal of this study was to compare both types of surgeries, LC-LAR LS with Knight-Griffen colorectal anastomosis and LC-LAR open with Trans-Anal Purse-String Suture Anastomosis (the TAPSSA group), by positioning a No-Coil transanal tube (SapiMed Spa, Alessandria, Italy), in terms of postoperative complications such as prolonged postoperative ileus (PPOI), anastomotic leak (AL), postoperative ileus (POI), and hospital stay.
The patients were divided into two groups: the first with 39 patients who underwent LC and LAR in LS with Knight-Griffen anastomosis (Knight-Griffen group) and the second with 38 patients who underwent LC and LAR by the open technique with the TAPSSA group. Only one patient who underwent the open technique suffered AL. POI was 3.76 ± 1.7 days in the TAPSSA group and 3.07 ± 1.3 days in the Knight-Griffen group. There were no statistically significant differences in terms of AL and POI between the two different groups.
The important point that preliminarily emerged from this retrospective study was that the two different techniques showed similarities in terms of AL and POI, and therefore, all the advantages reported in the previous studies pertaining to No-Coil also hold good in this study regardless of the surgical technique used. However, randomized controlled trials are needed to confirm these findings.
Background. Literature data suggest that cells such as mast cells (MCs), are involved in angiogenesis. MCs can stimulate angiogenesis by releasing of several proangiogenic cytokines stored in their ...cytoplasm. In particular MCs can release tryptase, a potent in vivo and in vitro proangiogenic factor. Nevertheless few data are available concerning the role of MCs positive to tryptase in primary pancreatic cancer angiogenesis. This study analyzed MCs and angiogenesis in primary tumour tissue from patients affected by pancreatic ductal adenocarcinoma (PDAC). Method. A series of 31 PDAC patients with stage T2-3N0-1M0 (by AJCC for Pancreas Cancer Staging 7th Edition) was selected and then underwent surgery. Tumour tissue samples were evaluated by means of immunohistochemistry and image analysis methods in terms of number of MCs positive to tryptase (MCDPT), area occupied by MCs positive to tryptase (MCAPT), microvascular density (MVD), and endothelial area (EA). The above parameters were related to each other and to the main clinicopathological features. Results. A significant correlation between MCDPT, MCAPT, MVD, and EA group was found by Pearson’s t-test analysis (r ranged from 0.69 to 0.81; P value ranged from 0.001 to 0.003). No other significant correlation was found. Conclusion. Our pilot data suggest that MCs positive to tryptase may play a role in PDAC angiogenesis and they could be further evaluated as a novel tumour biomarker and as a target of antiangiogenic therapy.
Background. Angiogenesis is a complex process involved in both growth and progression of several human and animal tumours. Tryptase is a serin protease stored in mast cells granules, which plays a ...role in tumour angiogenesis. Mast cells (MCs) can release tryptase following c-Kit receptor (c-KitR) activation. Method. In a series of 25 gastric cancer patients with stage T3N2-3M0 (by AJCC for Gastric Cancer 7th Edition), immunohistochemistry and image analysis methods were employed to evaluate in the tumour tissue the correlation between the number of mast cells positive to tryptase (MCPT), c-KitR expressing cells (c-KitR-EC), and microvascular density (MVD). Results. Data demonstrated a positive correlation between MCPT, c-KitR-EC, and MVD to each other. In tumour tissue the mean number of MCPT was 15, the mean number of c-KitR-EC was 20, and the mean number of MVD was 20. The Pearson test correlating MCPT and MVD, c-KitR-EC and MVD was significantly (r=0.64, P=0.001; r=0.66, P=0.041, resp.). Conclusion. In this pilot study, we suggest that MCPT and c-KitR-EC play a role in gastric cancer angiogenesis, so we think that several c-KitR or tryptase inhibitors such as gabexate mesilate and nafamostat mesilate might be evaluated in clinical trials as a new antiangiogenetic approach.
Background. We evaluated the HMGCoA reductase activity and LDL receptor levels in human colon cancer as well as the effects
of simvastatin on in vitro cell growth and apoptosis of DLD-1 and Caco2 ...cell lines. Materials and Methods: HMGCoA reductase
activity and LDL receptor were measured by radiochemical assay and ELISA method, respectively. Cell growth and apoptosis were
evaluated by MTT-test and DNA fragmentation analysis, respectively. Results: Higher HMGCoA reductase activity and LDL receptor
levels were detected in cancer than in normal mucosa. An up-regulation of HMGCoA reductase activity was detected in left-sided
tumors. Simvastatin treatment produced marked anti-proliferative and pro-aptotic effects in DLD-1. Cell growth inhibition,
but no apoptosis, was also evident in Caco2 cells. Conclusion: The cholesterol pathway is involved in colon malignant transformation.
Therapeutic strategies using HMGCoA reductase inhibitors as anti-cancer compounds should also take into consideration the
biological and clinical differences detected inside colon tracts.
AIM： To investigate H pylori expression in gastric cancer patients in relation to primary tumor angiogenic markers, such as microvessel density （MVD）, thymidine phosphorylase （TP）, vascular ...endothelial growth factor receptor-1 （VEGF-R1）, p53 and circulating VEGF levels.
METHODS： Angiogenic markers were analyzed immunohistochemically in 56 primary gastric cancers. H pylori cytotoxin （vacA） and the cytotoxin-associated gene （cagA） amplification were evaluated using PCR assay. Serum H pylori IgG antibodies and serum/plasma circulating VEGF levels were detected in 39 and 38 patients by ELISA, respectively.
RESULTS： A total of 69% of patients were positive for circulating IgG antibodies against Hpylori. cagA-positive H pylor/strains were found in 41% of gastric patients. vacA was found in 50% of patients; s1 strains were more highly expressed among vacA-positive patients. The presence of the s1 strain was significantly associated with cagA （P = 0.0001）. MVD was significantly correlated with both tumor VEGF expression （r = 0.361, P = 0.009） and serum VEGF levels （r = -0.347, P = 0.041）.Conversely, neither VEGF-R1 expression nor MVD was related to p53 expression. However, H pylori was not related to any angiogenic markers except for the plasma VEGF level （P = 0.026）.
CONCLUSION： H pylori antigen is related to higher plasma VEGF levels, but not to angiogenic characteristics. It can be hypothesized that the toxic effects of H pylori on angiogenesis occurs in early preclinical disease phase or in long-lasting aggressive infections, but only when high H pylori IgG levels are persistent.
Farnesyl diphosphate synthase (FPPs) produces FPP which is considered a branch-point intermediate in the synthesis of sterols and isoprenylated cellular metabolites. In this study we investigated ...whether detectable FPPs activity was present in human colorectal cancer (CRC), also evaluating in vitro the role of this enzyme in the growth and apoptosis of CRC cells by using Pamidronate (PAM), a FPPs activity inhibitor.
The activity level of FPPs was determined in CRC and the normal surrounding mucosa of 50 patients by radiochemical assay. The FPPs mRNA expression was investigated in 15 of 50 patients by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). K-ras mutation was evaluated using PCR and restriction enzyme analysis. Cell growth and apoptosis, after PAM treatment, in human CRC cell line DLD-1 were measured by MTT test and DNA fragmentation, respectively.
FPPs activity was detectable in human CRC. FPPs activity and its mRNA were significantly more abundant in cancer samples than in normal mucosa. In vitro PAM resulted in a significant reduction of cell growth and also gave rise to a marked proapoptotic effect.
This study provides the first evidence of the presence of FPPs activity in human CRC. Moreover, FPPs enzyme was found to play a significant role in colon cancer proliferation.
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