Search

Due to the aging of the populations of developed countries and a common occurrence of risk factors, it is increasingly probable that a patient may have both cancer and cardiovascular disease. In addition, cytotoxic agents and targeted therapies used to treat cancer, including classic chemotherapeutic agents, monoclonal antibodies that target tyrosine kinase receptors, small molecule tyrosine kinase inhibitors, and even antiangiogenic drugs and chemoprevention agents such as cyclooxygenase-2 inhibitors, all affect the cardiovascular system. One of the reasons is that many agents reach targets in the microenvironment and do not affect only the tumor. Combination therapy often amplifies cardiotoxicity, and radiotherapy can also cause heart problems, particularly when combined with chemotherapy. In the past, cardiotoxic risk was less evident, but it is increasingly an issue, particularly with combination therapy and adjuvant therapy. Today's oncologists must be fully aware of cardiovascular risks to avoid or prevent adverse cardiovascular effects, and cardiologists must now be ready to assist oncologists by performing evaluations relevant to the choice of therapy. There is a need for cooperation between these two areas and for the development of a novel discipline, which could be termed cardio-oncology or onco-cardiology. Here, we summarize the potential cardiovascular toxicities for a range of cancer chemotherapeutic and chemopreventive agents and emphasize the importance of evaluating cardiovascular risk when patients enter into trials and the need to develop guidelines that include collateral effects on the cardiovascular system. We also discuss mechanistic pathways and describe several potential protective agents that could be administered to patients with occult or overt risk for cardiovascular complications. [ABSTRACT FROM AUTHOR]

Background: Forensic analysis heavily relies on DNA analysis techniques, notably autosomal Single Nucleotide Polymorphisms (SNPs), to expedite the identification of unknown suspects through genomic database searches. However, the uniqueness of an individual's genome sequence designates it as Personal Identifiable Information (PII), subjecting it to stringent privacy regulations that can impede data access and analysis, as well as restrict the parties allowed to handle the data. Homomorphic Encryption (HE) emerges as a promising solution, enabling the execution of complex functions on encrypted data without the need for decryption. HE not only permits the processing of PII as soon as it is collected and encrypted, such as at a crime scene, but also expands the potential for data processing by multiple entities and artificial intelligence services., Methods: This study introduces HE-based privacy-preserving methods for SNP DNA analysis, offering a means to compute kinship scores for a set of genome queries while meticulously preserving data privacy. We present three distinct approaches, including one unsupervised and two supervised methods, all of which demonstrated exceptional performance in the iDASH 2023 Track 1 competition., Results: Our HE-based methods can rapidly predict 400 kinship scores from an encrypted database containing 2000 entries within seconds, capitalizing on advanced technologies like Intel AVX vector extensions, Intel HEXL, and Microsoft SEAL HE libraries. Crucially, all three methods achieve remarkable accuracy levels (ranging from 96% to 100%), as evaluated by the auROC score metric, while maintaining robust 128-bit security. These findings underscore the transformative potential of HE in both safeguarding genomic data privacy and streamlining precise DNA analysis., Conclusions: Results demonstrate that HE-based solutions can be computationally practical to protect genomic privacy during screening of candidate matches for further genealogy analysis in Forensic Genetic Genealogy (FGG)., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Computed tomography is frequently used to stage canine mast cell tumors (MCTs). The aims of this prospective, observational study were to describe the CT features of MCTs, to evaluate the performance of CT in detecting additional or incidental MCTs, to distinguish between cutaneous (cMCT) or subcutaneous (scMCT) MCTs, and to identify one or multiple sentinel lymph nodes (SLNs) by indirect CT lymphography (ICTL). Seventy-two dogs affected by 111 MCTs were included. The recorded parameters were: shape, size, attenuation (Hounsfield units [HU]), location (cutaneous or subcutaneous), and presence of fat stranding. The SLNs were compared with the regional lymph nodes and supplementary MCTs were registered. Mast cell tumors mostly appeared with well-defined margins (89%), round/oval shape (71%), homogeneous enhancement (90%) with a mean postcontrast density of 62.0 ± 23.4 HU and associated with fat stranding (43%). Cutaneous mast cell tumors were more frequently round (P = .003), whereas scMCTs were oval (P = .011) with a larger mean maximal diameter (2.91 ± 1.57 cm vs 1.46 ± 1.28 cm, P = .002) and more feeding vessels (77% vs 39% P = .044). Compared with histopathology, CT accuracy in differentiating cMCTs and sMCTs was 57%, with an interobserver agreement of 88% (three reviewers). Indirect CT lymphography showed the SLN in 82 of 85 (97%) cases, 32% of them not corresponding to the regional node. CT showed additional or incidental MCTs in 23 of 72 (32%) dogs. In conclusion, the common CT appearance of canine cMCTs and scMCTs is reported with some statistical differences between the two categories. CT is useful in identifying clinically undetected MCTs and SLNs, although it shows low accuracy in distinguishing between cMCT and scMCT., (© 2024 American College of Veterinary Radiology.)

Flex Robotic System allows a minimally invasive approach for transoral removal of submandibular salivary stones., Competing Interests: The authors have no conflict of interest to declare., (© 2022 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

The NTRK1 gene encodes Tropomyosin-related kinase A (TRKA), the high-affinity Nerve Growth Factor Receptor. NTRK1 was originally isolated from a colorectal carcinoma (CRC) sample as component of a somatic rearrangement (TPM3-NTRK1) resulting in expression of the oncogenic chimeric protein TPM3-TRKA, but there has been no subsequent report regarding the relevance of this oncogene in CRC. The KM12 human CRC cell line expresses the chimeric TPM3-TRKA protein and is hypersensitive to TRKA kinase inhibition. We report the detailed characterization of the TPM3-NTRK1 genomic rearrangement in KM12 cells and through a cellular screening approach, the identification of NMS-P626, a novel highly potent and selective TRKA inhibitor. NMS-P626 suppressed TPM3-TRKA phosphorylation and downstream signaling in KM12 cells and showed remarkable antitumor activity in mice bearing KM12 tumors. Finally, using quantitative reverse transcriptase PCR and immunohistochemistry (IHC) we identified the TPM3-NTRK1 rearrangement in a CRC clinical sample, therefore suggesting that this chromosomal translocation is indeed a low frequency recurring event in CRC and that such patients might benefit from therapy with TRKA kinase inhibitors., (Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Human metapneumovirus (hMPV) is an important aetiological agent of respiratory tract infection (RTI) in infants. Based on genetic differences, hMPVs are separated into two main groups, A and B, and two subgroups 1 and 2. To better understand the genetic diversity of hMPV, we analyzed 435 bp fragments of the F gene from 49 isolates obtained from a paediatric clinical centre in Northern Italy from 2005 to 2009. The phylogenetic analysis showed that our hMPV sequences clustered into five main clades (A1, A2a, A2b, B1, B2) statistically supported. Most of the strains belong to A2 (49%) and to B1 (28.5%) lineages. The intermixing in the phylogenetic tree showed no seasonal distribution between samples collected over a 5 year period. Mean genetic distances showed that clade A2 was more heterogeneous than others. In our F glycoprotein dataset we observed only two positively selected sites with an w value of 1.408 and 1.429, respectively, and 27 negatively selected sites. The two positively selected sites could be considered evolutionary "hot spots" because they were under positive selection and/or relaxed selective constraints. The abundant negatively selected sites reflect a high degree of conservation of F protein, probably necessary for viral infection.

The HER family of tyrosine kinase receptors includes several members that are clinically important targets in cancer therapies, in particular HER1 (the EGF receptor) and HER2, other members include HER3 and HER4. Trastuzumab, a humanized monoclonal antibody and lapatinib, a tyrosine kinase inhibitor, are drugs that target HER2, which is highly expressed in 20-30% of breast cancers. Trastuzumab is recommended as an adjuvant therapy for lymph node positive, HER2-positive breast cancers, or node-negative cancer with high-risk of recurrence, as well as in stage IV cancers. One serious side effect of trastuzumab is cardiomyocyte dysfunction, resulting in reduced heart contractile efficiency. The incidence of collateral effects on the heart with trastuzumab therapy increases in people with cardiovascular risk factors, heart disease and when combined with other chemotherapeutics. When cardiotoxicity was observed with trastuzumab, several studies have addressed potential cardiac damage of trastuzumab itself and lapatinib. The differences in cardiovascular effects of these two compounds are somewhat unexpected and suggest distinct mechanisms of action, which have clear implications in clinical application and prevention of cardiotoxicity in cardio-oncological approaches.

Background: Colorectal cancer can be efficiently treated when found at early stages, thus the search for novel markers is of paramount importance. Since inflammation is associated with cancer progression and angiogenesis, we investigated expression of cytokines like IL-6 and other mediators that play a key role in the innate immune system, in particular toll like receptor 4 (TLR4), in the microenvironment of lesions from different stages of colon disease progression, from ulcerative colitis to adenoma and adenocarcinoma to find useful markers., Methods: The presence of inflammatory cells and expression of key cytokines involved in the inflammation process were quantified by immunohistochemistry in specific tissue compartments (epithelial, stromal, endothelial) by immunohistochemistry. A murine azoxymethane/dextran sulfate model in which Tir8, a negative regulator of the inflammatory response, was ablated was used to confirm the clinical observations. 116 Archival tissue samples from patients with different stages of colorectal disease: 13 cases of ulcerative colitis (UC), 34 tubular or tubulo-villous adenomas (AD), and 53 infiltrating adenocarcinomas. 16 specimens of healthy mucosa surgically removed with the cancerous tissue were used as a control., Results: The differences between healthy tissues and the diverse lesions was characterized by a marked inflammatory-angiogenic reaction, with significantly (P < 0.05) higher numbers of CD68, CD15, and CD31 expressing cells in all diseased tissues that correlated with increasing grade of malignancy. We noted down-regulation of a potential modulator molecule, Hepatocyte Growth Factor, in all diseased tissues (P < 0.05). TLR-4 and IL6 expression in the tumor microenvironment were associated with adenocarcinoma in human samples and in the murine model. We found that adenocarcinoma patients (pT1-4) with higher TLR-4 expression in stromal compartment had a significantly increased risk in disease progression. In those patients with a diagnosis of pT3 (33 cases) colon cancer, those with very high levels of TLR-4 in the tumor stroma relapsed significantly earlier than those with lower expression levels., Conclusions: These data suggest that high TLR-4 expression in the tumor microenvironment represents a possible marker of disease progression in colon cancer.

Objective: The goal of the OSCAR programme is to evaluate the performances of genotypic HIV-1 tropism testing in clinical practice using the enhanced sensitivity version of Trofile (ESTA) as reference-assay., Methods: HIV-1 coreceptor-usage was assessed using plasma samples from 406 HIV-1 infected patients by ESTA and by gp120 V3 population-sequencing followed by Geno2pheno (set at a False Positive Rate [FPR] of 10% and 5%)., Results: ESTA was successful in 365 (89.9%) samples indicating R5 in 254 (69.6%), and DM/X4 in 111 (30.4% of samples (104 [28.5%] DM and 7 [1.9%] X4). Genotypic-testing successfully assessed viral tropism for all 406 samples, including the 41 with undetermined result by ESTA. Genotypic-tropism testing at a FPR of 5% and 10% was 81.1% and 78.4% concordant with ESTA, respectively. Despite a sensitivity of 48.7% and 55.9% at a FPR of 5% and 10%, respectively, a high concordance (specificity: 95.3% for FPR of 5% and 88.2% for FPR of 10%) between genotypic-tropism testing and ESTA was reached in the detection of R5-tropic viruses., Conclusion: Our results are in line with other European studies, and support the routine use of genotypic tropism testing in clinical-settings for monitoring of HIV-1 infected patients candidate to or failing CCR5-antagonists.

Single-wall carbon nanotubes (SWCNTs) could be promising delivery vehicles for cancer therapy. These carriers are generally introduced intravenously, however, little is known of their interactions with endothelial cells, the cells lining vessels and mediating clearance of nanoparticles. Here we show that SWCNTs of 1 to 5 microm in length, both "pristine" and functionalized by oxidation, had limited toxicity for endothelial cells in vitro as determined by growth, migration morphogenesis, and survival assays. Endothelial cells transiently took up SWCNTs, and several lines of data indicated that they were associated with an enhanced acidic vesicle compartment within the endothelial cells. Our findings of SWCNT interactions with endothelial cells suggest these may be optimal vehicles for targeting the vasculature and potential carriers of anti-angiogenic drugs. The implications on their biological activity must be taken into account when considering the use of these nanoparticles for therapeutic delivery of drugs., From the Clinical Editor: Interactions of single walled carbon nanotubes (SWCNTs) with endothelial cells following IV administration remains unclear. Functionalized and naïve SWCNTs of 1-5 mm in length had limited toxicity to endothelial cells in vitro. Endothelial cells transiently took up SWCNTs and were associated with an enhanced acidic vesicle compartment within the cells. These findings suggest that SWCNTs may be promising vehicles for targeting the vasculature and potential carriers of anti-angiogenic drugs., (Copyright 2010 Elsevier Inc. All rights reserved.)

The role of transforming growth factor beta (TGFbeta) in tumor promotion and in angiogenesis is context-dependent. While TGFbeta prevents tumor growth and angiogenesis in early phases of tumor development, evidence is accumulating about its pro-angiogenic and tumor promotion activities in late-stages of tumor progression. Here we have studied, in an experimental context previously reported to disclose the pro-angiogenic effects of TGFbeta, the blocking activity of TGFbeta antagonist peptides. In agreement with previous results, we have observed that TGFbeta exerts a powerful pro-angiogenic activity on human normal dermal microvascular endothelial cells (MVEC), by promoting invasion and capillary morphogenesis in Matrigel. No apoptotic activity of TGFbeta was observed. By RT-PCR we have shown that TGFbeta up-regulates expression not only of plasminogen activator inhibitor type-1 (PAI-1), but also of the urokinase-type plasminogen activator receptor (uPAR), whose inhibition by specific antibodies blunted the TGFbeta angiogenic response in vitro. The SMAD2/3 and FAK signaling pathways were activated by TGFbeta in MVEC, as an early and late response, respectively. The use of two different TGFbeta1 antagonist peptides, derived from TGFbeta type III receptor sequence and 15-mer phage display technology, inhibited the signaling and pro-angiogenic response in vitro, as well as uPAR and PAI-1 up-regulation of MVEC following TGFbeta challenge. The anti-angiogenic properties of both inhibitors were evident also in the in vivo TGFbeta Matrigel Sponge Assay. These results may be relevant to develop a potentially fruitful strategy for the therapy of late-stage-associated tumor angiogenesis.

Angiogenesis is the base for solid tumour growth and dissemination, and anti-angiogenic drugs have been demonstrated to be active in clinical trials. In addition, it has become increasingly clear that inflammation is a key component in tumour insurgence. Chemoprevention focuses on the primary or secondary prevention of cancer using natural or synthetic agents that usually show mild or no collateral effects. We have noted that angiogenesis, particularly 'inflammatory angiogenesis', is a common target of many chemopreventive molecules, where they most likely suppress the angiogenic switch in pre-malignant tumours, a concept we have termed 'angioprevention'. We have shown that various molecules, such as flavonoids, antioxidants and retinoids, act in the tumour microenvironment inhibiting the recruitment and/or activation of endothelial cells and phagocytes of the innate immunity. We have recently assessed the activity of novel compounds derived from the oleanolic acid triterpenoid, called CDDO-Me and CDDO-Imm. These compounds show a potent anti-angiogenic activity at low dosages. In vivo they inhibit angiogenesis in the Matrigel sponge assay and in KS-Imm (an immortalized Kaposi's sarcoma cell line) tumour growth. In vitro they are able to prevent endothelial cell tubulogenesis when cultured on Matrigel. In human umbilical vein endothelial (HUVE) cells these compounds can inhibit the activation of the extracellular signal-regulated kinase ERK1/2 pathway after stimulation with vascular endothelial growth factor (VEGF). Moreover, from immunofluorescence experiments we observed that treatment with these triterpenoids prevents nuclear factor NF-kappaB translocation into the nucleus and thereby the activation of downstream pathways. The particularly potent anti-angiogenic activity seen in vivo suggest that CDDO-Me may be interacting with an important network of molecular and cellular targets, on endothelial cells, and could be employed for 'angioprevention'. These substances are being assessed in phase I trials in humans in the United States.

We show that the synthetic oleanane triterpenoid, CDDO-methyl ester (CDDO-Me; methyl 2-cyano-3,12-dioxoolean-1,9-dien-28-oate) is an effective agent for suppressing angiogenesis, both in cell culture and in vivo. The potency of CDDO-Me is particularly striking when dosed in vivo to inhibit the angiogenic effects of vascular endothelial growth factor and tumor necrosis factor-alpha in Matrigel sponge assays; activity is seen at i.p. doses of CDDO-Me as low as 0.003 mg/kg of body weight. If the Matrigel sponges are impregnated with CDDO-Me just before implantation in the mice, picomolar doses of CDDO-Me will suppress angiogenesis. CDDO-Me also inhibits growth of endothelial cells in monolayer cultures and suppresses neovascular morphogenesis in three-dimensional cultures, but significantly higher doses (50-200 nmol/L) are required. We also show antiangiogenic effects of CDDO-Me on xenografts of Kaposi's sarcoma cells in immunocompromised mice, using CD31 as a marker. Several known individual molecular targets of CDDO-Me and related triterpenoids that are relevant to all of these findings include nuclear factor-kappaB signaling, signal transducers and activators of transcription signaling, and transforming growth factor-beta signaling, as well as Keap1, the endogenous inhibitor of the transcription factor Nrf2. However, the particularly potent antiangiogenic activity seen in vivo in the present experiments suggest that CDDO-Me, as an angioprevention agent, may be interacting with an entire network of molecular and cellular targets, rather than at a single molecular locus or in a single-cell type.

Ocular tumors such as retinoblastoma and uveal melanoma have devastating effects on vision. Patients with uveal melanoma also have low 5-year survival rates, thus new therapeutic modalities are necessary. As both retinoblastoma and uveal melanoma are highly vascular, we tested application of a gene transduction approach with a potent TH1 cytokine also endowed with strong anti-angiogenic activity, Interleukin-12 (IL-12). Gene transfer into murine 99E1 uveal melanoma-like cells, while having no effects on growth in vitro, essentially blocked subcutaneous tumor growth in vivo without evident signs of toxicity. Orthotopic intraocular injection resulted in invasive tumors that destroyed ocular architecture by the control cells while the IL-12 transduced cells rarely formed tumors. Histological analysis revealed highly invasive and angiogenic tumor growth in the controls and poorly vascularized tumors in the presence of IL-12. The tumor repression effect could be reproduced by a systemic anti-angiogenic effect, where controlateral injection of IL-12 expressing cells strongly repressed growth in tumors formed by parental 99E1 cells. This was associated with significantly lowered tumor vessel densities, a trend toward lower VEGF levels in the lesion, and significantly decreased NK cells in the parental tumors exposed to systemic IL-12. Taken together, our data suggest that IL-12 gene transfer can provide anti-angiogenic effects without toxicity and may be particularly suited for therapy of vascularized ocular tumors.

Aim: Gallbladder and gastrointestinal motility defects exist in gallstones patients and to a lesser extent in pigment gallstone patients. To investigated the role of gallbladder and gastrointestinal motility disorders in pigment gallstone formation in beta-thalassemia major., Methods: Twenty-three patients with beta-thalassemia major (16 females; age range 18-37 years) and 70 controls (47 females, age range 18-40 years) were studied for gallbladder and gastric emptying (functional ultrasonography), orocecal transit (OCTT, H(2)-breath test), autonomic dysfunction (sweat-spot, cardiorespiratory reflex tests), bowel habits, gastrointestinal symptoms and quality of life (all with questionnaires). Gallbladder content (ultrasonography) was examined before and during 8-12 mo follow-up., Results: Gallstones and/or biliary sludge were found in 13 (56%) patients. beta-thalassemia major patients had increased fasting (38.0+/-4.8 mL vs 20.3+/-0.7 mL, P = 0.0001) and residual (7.9+/-1.3 mL vs 5.1+/-0.3 mL, P = 0.002) volume and slightly slower emptying (24.9+/-1.7 min vs 20.1+/-0.7 min, P = 0.04) of the gallbladder, together with longer OCTT (132.2+/-7.8 min vs 99.7+/-2.3 min, P = 0.00003) than controls. No differences in gastric emptying and bowel habits were found. Also, patients had higher dyspepsia (score: 6.7+/-1.2 vs 4.9+/-0.2, P = 0.027), greater appetite (P = 0.000004) and lower health perception (P = 0.00002) than controls. Autonomic dysfunction was diagnosed in 52% of patients (positive tests: 76.2% and 66.7% for parasympathetic and sympathetic involvement, respectively). Patients developing sludge during follow-up (38%, 2 with prior stones) had increased fasting and residual gallbladder volume., Conclusion: Adult beta-thalassemia major patients have gallbladder dysmotility associated with delayed small intestinal transit and autonomic dysfunction. These abnormalities apparently contribute together with haemolytic hyperbilirubinemia to the pathogenesis of pigment gallstones/sludge in beta-thalassemia major.

Background: A systemic reaction to mycobacteria biases the balance of T helper cell types 1 and 2 toward T helper cell type 1. BCG vaccination mimics some characteristics of mycobacterial infection. Children who have undergone tuberculin conversion after BCG vaccination seem to be more likely to lose their atopic symptoms. Inhibition of both allergic response and airway hyperreactivity after vaccination for mycobacteria has been observed in animal experiments., Objective: To evaluate the effects that BCG vaccination has on the serological status of allergic people., Participants and Methods: This study included 20 volunteers with a history of allergic rhinitis who were required to undergo BCG vaccination by Italian law. Epicutaneous allergy testing with a panel of common seasonal and perennial inhalational allergens and 2 blood withdrawals were performed. The serum total IgE levels and the serum allergen-specific IgE levels of each individual were measured just before BCG vaccination and again 4 months later. Total IgE levels were determined using the paper radioimmunosorbent test, and allergen-specific IgE levels were determined using the radioallergosorbent test., Results: Total IgE and allergen-specific IgE levels were significantly decreased after BCG vaccination (P =.004 and P<.001, respectively)., Conclusion: BCG, an effective stimulus for cell-mediated immunity, deserves further study to evaluate its ability to modulate the immune response associated with allergic rhinitis.

The excessive content of toxic elements in the human environment is associated with the etiology of a number of diseases. Soils' pollutants decontamination regards the main industrialised countries. Heavy metals represent the main problem for soil pollution characterisation. The first approach for pollution evaluation is the determination of total metal concentration; the evaluation of their bioavailability is required for a correct knowledge of the environmental risk. In the present work is shown the procedure to evaluate the sites, which require decontamination and which need the following data: knowledge of the threshold for each metal in the soil and its range, chemical analysis of the components, determination of bioavailability and soil destination. The bioavailability is easily calculated by the procedure of aimed extractions.

Background: The aim of this study was to evaluate the main parameters provided by the static stabilometric test (mean X, mean Y, mean velocity, length of tracing, standard deviation of velocity, ellipse area) in the follow-up of patients suffering from skeletal occlusive pathology undergoing orthognathodontic surgery to confirm the re-establishment of postural equilibrium., Methods: Fifteen patients with skeletal dysgnathia were correlated with a group of 10 healthy subjects. The same parameters were analysed in the dysgnathic subjects at 6 and 12 months after surgical correction. The patients enrolled in this study underwent surgery at the Division of Maxillofacial surgery of Turin University. Student's "t"-test and multivariate statistical analysis (Cox regression) were used for the statistical analysis of results., Results: A significant variability was noted in some of the main parameters analysed (mean X, mean Y, tracing length) between the two populations (healthy and dysgnathic) compared to visual signs (eyes opened-closed). The change in stabilometric values within the group of dysgnathic patients was highly significant 6 and 12 months after surgery, not only in terms of visual signs but also the cervical component (retroflexion of the head), above all the value of mean Y (p = 0.001)., Conclusions: An analysis of these results shows that static stabilometry can be a valuable aid both during the preoperative evaluation and during the follow-up in patients undergoing jaw surgery since it can quantify the improvement of body balance.

The aim of this study was to evaluate the role of angiogenesis in the progression of laryngeal squamous cell carcinoma (LSCC). We correlated disease-free survival with microvessel count (MC) in the hot spot areas of 97 randomly selected caucasian males with LSCC followed for 60 to 90 months after surgery with or without radiotherapy. The results obtained indicate that: a) MC higher than 130 microvessels/mm2 is a cut-off value that distinguished patients who relapsed during the follow up period; b) multivariated analysis indicates that MC (p < 0.00001) is an independent predictor of disease free-survival; c) multivariated analysis selectively done on cases with relapse demonstrates that MC correlates with the presence of metastasis (or/and M) with local relapse (T). We suggest that MC is useful in the assessment of prognosis in LSCC and probably will permit selection of patients that could benefit from anti-angiogenic therapy associated with chemotherapy and/or radiotherapy.