Biomedical subjects
Publications and source records attributed to O Gallo.
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We evaluated the role of COX-2 pathway in 35 head and neck cancers (HNCs) by analyzing COX-2 expression and prostaglandin E2 (PGE2) production in relation to tumor angiogenesis and lymph node metastasis. COX-2 activity was also correlated to vascular endothelial growth factor (VEGF) mRNA and protein expression. COX-2 mRNA and protein expression was higher in tumor samples than in normal mucosa. PGE2 levels were higher in the tumor front zone in comparison with tumor core and normal mucosa (P<.0001). Specimens from patients with lymph node metastasis exhibited higher COX-2 protein expression (P=.0074), PGE2 levels (P=.0011) and microvessel density (P<.0001) than specimens from patients without metastasis. A significant correlation between COX-2 and tumor vascularization (r(s)=0.450, P=.007) as well as between COX-2 and microvessel density with VEGF expression in tumor tissues was found (r(s)=0.450, P=.007; r(s)=0.620, P=.0001, respectively). The induction of COX-2 mRNA and PGE2 synthesis by EGF and Escherichia coli lipopolysaccharide (LPS) in A-431 and SCC-9 cell lines, resulted in an increase in VEGF mRNA and protein production. Indomethacin and celecoxib reversed the EGF- and LPS-dependent COX-2, VEGF, and PGE2 increases. This study suggests a central role of COX-2 pathway in HNC angiogenesis by modulating VEGF production and indicates that COX-2 inhibitors may be useful in HNC treatment.
Head and neck cancer (HNC) patients are at high risk of developing second primary tumors of the upper aerodigestive tract and this is a chief cause of death. Genomic instability reflecting the propensity and the susceptibility of the genome to acquire multiple alterations is considered a driving force behind multiple carcinogenesis and the alterations of the length of single repetitive genomic sequences or microsatellite instability (MI), implicating impaired DNA repair mechanisms, and could be a sensitive marker for assessing genomic instability in multiple HNC. To investigate whether a genetic defect(s) involving the mismatch repair system constitutes a risk factor in patients with multiple head and neck cancer, we examined replication errors (RER) at 10 microsatellite loci in 21 primary and 5 second primary cancers in 21 patients with multiple malignancies of the upper aerodigestive tract, in comparison with match-paired primary HNC from patients without multiple malignancies. A RER+ phenotype (alterations at > or =2 loci) was observed at 10 microsatellite alterations on chromosomes 2, 3, 11, 17 in at least one tumor from 15 out of 21 (71.5%) patients with multiple primary cancers but only in 11 tumors from 40 (27.5%) HNC patients with single cancer (P=0.001). A RER+ phenotype was also associated with a positive familial cancer history (P=0.046). Our results suggest that a genetic instability may play an important role in the pathogenesis of multiple primary cancers and that testing for MI in a primary HNC may be useful in detecting patients with high risk for developing multiple malignancies of the upper aerodigestive tract.
BACKGROUND: In head and neck squamous cell carcinoma, distinguishing second primary tumours and recurrences may help to orient clinical decisions concerning therapy. PATIENTS AND METHODS: A panel of eight microsatellite markers was used to analyse the loss of heterozygosity and genomic instability in a selected group of 32 patients experiencing a recurrence after having undergone surgery for oral or oropharyngeal carcinoma, in order to establish the clonality and origin of the recurrence. RESULTS: Twenty-three patients showed genetic changes in primary and/or relapsing tumour DNA: clonally-related patterns were detected in six cases, whereas the different patterns between paired tumours indicated the presence of a second primary tumour in 17 cases. None of the markers was informative in nine cases. CONCLUSION: Our observations suggest that only a small proportion of patients have primary and secondary tumours developing from a single contiguous altered field (thus indicating a common clonal origin), whereas the metachronous tumour arises in unrelated fields in the majority of cases.
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Aneurysm of the internal carotid artery is rarely mentioned as a cause of epistaxis. This condition is quite rare but it is important to consider aneurysms in the etiology of epistaxis because of their high mortality rate and since they require management quite different from that of epistaxis of other origins. After arteriosclerosis the most frequent cause of an aneurysm of the internal carotid artery is a closed or penetrating craniofacial trauma injuring the artery. This leads to subsequent aneurysmal dilation of the cavernous and petrous portions of the artery itself. Aneurysms of the cavernous portion of the artery are more frequent. In this location the aneurysm has a close anatomical relationship with the sphenoid sinus as well as the nasal fossae. In the present paper two cases of traumatic intracavernous carotid aneurysms presenting epistaxis are described. In the first case, reported 25 years ago, the diagnosis was made on an autoptic table in young man who died after two severe episodes of massive nasal hemorrhage. The second case involved a 17-year-old man with a severe epistaxis reported one month after a close craniofacial trauma. An intracranial carotid pathology was suspected because of the recurrence of nose-bleeding and the history of reduced visual activity. Therefore angiography was performed which revealed a small aneurysm of the intracavernous segment of the left internal carotid artery. Subsequently, an endovascular balloon embolization of the aneurysm was successful, preserving the parent artery. The importance of considering aneurysms in the differential diagnosis of massive epistaxis is emphasized.
Cancers of the hypopharynx (pyriform fossa, post-cricoid area and posterior wall) and larynx show a high tendency to invade the cervical lymph nodes. Such nodal extension is a well known prognostic factor. In general, those lesions that are in well-lateralized primary sites (pyriform sinus, aryepiglottic fold...) tend to metastasize to the ipsilateral side of the neck. This concept, however, is fraught with exceptions; any lesion, especially with ipsilateral metastases, creates a risk for contralateral node involvement. The present study is based on a retrospective review of 450 clinical records of patients affected by well-lateralized laryngeal (301 pt.) and hypopharyngeal (149 pt.) carcinomas. The incidence of contralateral metastases was analyzed for this group; 25 out of 310 patients with laryngeal cancer (8.3%) and 20 out of 149 with hypopharyngeal cancer (13.4%) showed metastatic involvement of the contralateral neck. In patients with laterally oriented primary lesions, the initial appearance of cervical adenopathy is rarely contralateral since contralaterality is almost a manifestation of bilaterality of metastases. A contralateral disease is rarely possible even if the homolateral neck has been surgically treated. This is because of shunted lymph flow through the submental and submandibular lymphatics. Isolated contralateral disease was only found in 4 patients (1.3%): such data do not suggest any systematic, elective treatment of the contralateral neck NO in patients with unilateral laryngeal and hypopharyngeal cancers.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.