Expression of galectins in head and neck squamous cell carcinoma

BACKGROUND: Galectins are carbohydrate-binding proteins thought to be important for cell growth and differentiation, whose expression is altered in some tumors with aggressive phenotype. Our objective was to evaluate the expression of galectins in head and neck squamous cell carcinoma (HNSCC). METHODS: Fourteen HNSCC cell lines and four primary tumor specimens were evaluated using immunoblotting, and immunohistochemical analysis was performed on 35 primary HNSCCs. RESULTS: Galectin-1 and galectin-3 were expressed in most HNSCC cell lines and primary tumor specimens. Galectin-1 was detected in the basal layer of normal adjacent mucosa, in connective tissue stroma, and at the periphery of invasive tumor islands. Galectin-3 localized to superficial mucosal layers, and adjacent to keratin pearls in invasive carcinoma. CONCLUSIONS: Galectins are manifested in HNSCC tumors and are localized to the cell surface, where they may participate in cellular interactions. The expression pattern of galectins appears to be associated with degree of squamous differentiation, suggesting a potential role for galectins as biologic and differentiation markers in HNSCC.     

Radiologic diagnosis and staging of head and neck squamous cell carcinoma

The predominant extracranial head and neck cancer in adults is squamous cell carcinoma. The purpose of this article is to discuss the radiographic evaluation of these patients with computed tomography (CT) or magnetic resonance (MR) imaging prior to therapeutic intervention. Specific focus is given to the efficacy of CT and MR imaging, as an adjunct to clinical staging, for evaluation of the primary tumor, and metastatic adenopathy. MR imaging, because of its improved soft tissue contrast and multiplanar capability, is probably superior to CT for evaluation of the primary tumor in patients with squamous cell carcinoma. CT, however, remains the gold standard for identifying metastatic adenopathy and in most institutions remains the study of choice for evaluating this patient population.     

Vascular endothelial growth factor expression in head and neck squamous cell carcinoma

BACKGROUND: Angiogenesis is an essential process required for growth and metastasis in cancer. In breast, gastric, and prostate cancer, vascular endothelial growth factor (VEGF) has been implicated in angiogenesis; however, little is known about VEGF in HNSCC. In this study, we hypothesize that VEGF is present in elevated levels in HNSCC and may therefore play a role in promoting angiogenesis. METHODS: We obtained tumor tissue from 63 HNSCC patients undergoing primary resection. All tissue samples were analyzed by immunohistochemistry (IHC) techniques for the presence and localization of VEGF; however, only 36 had sufficient amounts of tissue for quantitative analysis of VEGF by ELISA. Nine control specimens taken from patients undergoing uvulopalatopharyngoplasty were also analyzed. RESULTS: In all 63 of our patient samples we found VEGF to be present and localized to the cancer cells and endothelial cells. The poorly differentiated cancer cells stained more intensely in comparison with the well-differentiated ones. There was a 20-fold increase in the patient levels when compared with controls levels (P > or =0.05). Analysis by enzyme-linked immunosorbent assay revealed elevated mean levels of VEGF (241 +/- 326 pg/mg total protein [TP]) with a range of 2 to 1484 pg/mg TP. The control specimens had mean levels of 13 +/- 11 pg/mg TP and a range of 1 to 78 pg/mg TP. Patients who exhibited higher levels of VEGF tended to have a higher rate of disease recurrence (P < or =0.048) and shorter disease-free interval (P < or =0.05). CONCLUSIONS: The expression of VEGF in elevated levels in the HNSCC tumor microenvironment appears to be associated with more aggressive disease. Based on our results, VEGF may be an important angiogenic factor associated with cancer cells and endothelial cells in HNSCC. Further studies are needed to better define the role of VEGF in HNSCC and its role as a potential target for therapeutic intervention.     

Nitric oxide synthase activity in human squamous cell carcinoma of the head and neck

A continuous fluorometric assay for tryptophan hydroxylase activity based on the different spectral characteristics of tryptophan and 5-hydroxytryptophan is presented. Hydroxylation of tryptophan at the 5-position results in a large increase in the fluorescence of the molecule. The assay selectively monitors the fluorescence yield of 5-hydroxytryptophan by exciting the reaction mix at 300 nm. The rate of increase of the emission signal was found to be directly proportional to the enzyme concentration. Inner filter effects due to quinonoid dihydropterin accumulation were eliminated by the inclusion of a thiol reductant. Activity measured using this assay method was found to be the same as that determined by established discontinuous HPLC assay methods. The application of the assay to routine activity measurements and to steady-state determinations with the substrates tryptophan and tetrahydropterin is described.     

Serum levels of tumor necrosis factor in squamous cell carcinoma of the head and neck

Two experiments were conducted to study the effect(s) of Borrelia burgdorferi and its metabolites (toxicants?) on canine spermatozoa, using B burgdorferi type strain B-31 and ejaculates from 5 sexually mature dogs. In Experiment 1 the spirochetes were cocultured with semen and incubated under various conditions, and in Experiment 2 the spirochetes were sonicated to release the metabolites/toxicants. The sonicate was then cultured with the semen. The parameters investigated were kinematics and percentage of sperm motility, morphology, and sperm response to the hypoosmotic swelling test and acrosome reaction. There were no visible physical interaction between either dead or motile spirochetes and viable or dead spermatozoa. Neither the spirochetes per se nor their metabolites/toxicants had any significant adverse effect on the functional and morphological characteristics of the canine spermatozoa. It is possible that the exposure times for incubation were not long enough for metabolites or toxicants in the sonicate to significantly affect sperm characteristics. Some investigators have reported that B burgdorferi contain biologically active LPS-like endotoxins. It is also likely that storage denatures B burgdorferi metabolites and other intracellular products in the sonicate and, thus, negates any effects the medium or the sonicate might have on the spermatozoa. The apparent lack of effect suggests that either peripheral metabolism or action on other organ(s) may be required for deleterious action of the spirochetes and/or their toxicants on spermatozoa. It was concluded that B burgdorferi and/or metabolites/toxicants do not have any significant deleterious effects on the functional and morphological characteristics of the postspermatogenic spermatozoa. Interaction of the spirochetes with in vivo conditions may be needed to adversely affect spermatozoa.     

Paclitaxel enhances in vitro radiosensitivity of squamous carcinoma cell lines of the head and neck

Squamous cell carcinoma of the head and neck is the fourth most common cancer in the United States, and therapy for very advanced cases is relatively ineffective. Paclitaxel has activity against cancers of the breast, lung, prostate, cervix, and ovary. The activity of paclitaxel for squamous cell carcinoma of the head and neck is less certain, and results of its radiosensitization properties have been variable. The radiation responses of two squamous carcinomas, SCC-9 (oropharynx) and HEP-2 (larynx), were examined to determine the radiosensitizing potential of paclitaxel. In vitro exposures for 24 and 48 h with paclitaxel concentrations of 10(-4) to 6 x 10(-2) microg/ml were followed by irradiation of 0.1-10 Gy. Percent survival was calculated by colony count, and the paclitaxel-radiation interaction was quantitated by the median effect principle and the combination index method of Chou and Talalay. The paclitaxel-radiation combination resulted in multiphasic interactions in both 24 and 48 h paclitaxel pretreatment in SCC-9 and HEP-2 cell lines. In general there was slight synergism [combination index (CI) <1] at low dose-low effect levels (e.g., at a paclitaxel concentration of 0.002 microg/ml or lower and radiation of 0.1-0.3 Gy), moderate antagonism (CI >1) at median dose ranges and strong synergism (CI <1) at high dose ranges (e.g., at a paclitaxel concentration of 0.012-0.06 microg/ml and radiation doses of 3-10 Gy), especially at a surviving fraction of <0.1, which is therapeutically relevant. The median effect principle and combination index method provided a simple way to quantitate the synergism or antagonism of a paclitaxel-radiation interaction under various conditions. This analysis demonstrated that paclitaxel-radiation synergy exists at doses that are readily achievable in the clinical scenario for both agents and that greater synergy occurred at high dose-high effect levels. These results suggest that the combination of both therapies should be explored further in clinical trials assessing the treatment of squamous cell carcinomas of the head and neck.     

Prognostic factors of cervical lymph node metastasis in head and neck squamous cell carcinoma

AIMS AND BACKGROUND: The metastatic spread of squamous cell carcinoma of the head and neck (SCCHN) to the cervical lymph nodes is a negative prognostic factor in terms of survival. We have used multivariate analysis to identify the possible prognostic significance of a number of clinical and pathological characteristics in relation to possible involvement of the cervical lymph nodes in a series of 396 patients. METHOD: 396 patients with SCCHN were studied. Variables regarding the patient, the carcinoma and histology were analysed by multivariate analysis using BMDP's PLR programme. RESULTS: Some variables appear to represent predisposing factors for tumor spread to the lymph nodes: tumor site (supraglottic larynx: P = 0.005; base of the tongue: P = 0.02; hypopharynx: P = 0.02), grading (P = 0.001), and a number of histological parameters (lower degree of histological differentiation: P = 0.001; vascular permeation: P = 0.04; perineural invasion: P < 0.05; prevalently plasmocytic infiltrate: P < 0.05). CONCLUSION: The identification of cases at risk for metastasis can be improved by the assessment of prognostic factors, with a consequent improvement in treatment strategies.     

Microsatellite instability associated with primary head and neck cancers and secondary esophageal cancers

BACKGROUND: It is common that patients with head and neck cancers have secondary malignant neoplasm of esophageal cancer. METHODS: To know the genetic background of the development of these secondary cancers, we performed microsatellite assay at six loci and immunohistochemical analysis on head and neck cancers of eight patients with esophageal cancer and on those of 19 patients without esophageal cancer. RESULTS: Replication error (RER) at more than two loci was observed in two (25%) of eight double cancer patients, whereas it was not observed in the patients without the secondary cancer. Immunohistochemically, overexpression of cyclin D1 was detected in two (25%) of eight double cancer cases and in two (11%) of 19 non-double cancer cases, respectively, the incidence showing a higher tendency in the former. CONCLUSIONS: The results suggest that microsatellite instability may be implicated in the development of head and neck double cancers and that RER (+) phenotype may serve as a biomarker to predict the development of secondary esophageal cancer in patients with head and neck cancer.     

Neoplastic fixation to the prevertebral compartment by squamous cell carcinoma of the head and neck

OBJECTIVE: The purpose of this study was to determine the accuracy of MR imaging in determining fixation of squamous cell carcinomas to the prevertebral space. MATERIALS AND METHODS: MR images of 15 patients with large pharyngeal carcinoma (n = 13) or laryngeal carcinomas with pharyngeal extension (n = 2) were retrospectively reviewed independently by two head and neck radiologists who were unaware of the surgical findings. MR images were evaluated for four criteria in the prevertebral longus muscle complex: muscle concavity, irregular tumor-muscle interface, T2 hyperintensity, and enhancement. All patients underwent panendoscopy where fixation or mobility of the tumor relative to the prevertebral fascia was assessed by manual manipulation. Tumors in six patients were fixed to the prevertebral space and inoperable. In nine patients whose tumors were not fixed, open neck explorations were performed and tumors were resected in seven patients. MR findings were compared with panendoscopy in all patients and with intraoperative assessment in nine patients. RESULTS: Eleven of 15 patients had at least two of the MR imaging criteria present. None of the MR findings were both sensitive and specific for tumor fixation. Although muscle concavity and enhancement each had a sensitivity of 88%, both criteria suffered from low specificity (14% and 29%, respectively). An irregular tumor-muscle interface and muscle T2 hyperintensity were criteria that suffered from both low sensitivity and specificity. Accuracy of the imaging criteria independently ranged from 53% to 60%. CONCLUSION: Although abnormal muscle contour, T2 hyperintensity, and enhancement are frequently present in neck carcinomas that are fixed to the prevertebral space, these findings may also be present in patients in whom the tumor is mobile and resectable. MR imaging may not be able to differentiate between neoplastic fixation and nonneoplastic changes in the prevertebral space.     

MR imaging in squamous cell carcinoma of the head and neck with no palpable lymph nodes

PURPOSE: To assess the efficacy of MR imaging in the detection of lymph node metastasis in patients with no palpable lymph nodes ("N0 neck") who have squamous cell carcinoma of the head and neck region. MATERIAL AND METHODS: MR neck imagings in 18 patients who underwent neck dissection (bilaterally in 2) for squamous cell carcinoma of the head and neck region were examined preoperatively for the purpose of detecting lymph node metastases. The imaging features taken into consideration were: size (cutoff point 10 mm), grouping, presence of central necrosis, and appearance of extracapsular spread. The MR examinations comprised spin-echo T1- and T2-weighted sequences. The MR findings were compared with those of surgery and histopathological examination. RESULTS: MR suggested metastatic lymph node involvement in 5 necks. In 2 of these, central necrosis was seen in the enlarged lymph nodes. In a third, a grouping of the lymph nodes was noted. Extracapsular spread was not present. Histopathological examination revealed metastatic lymph nodes in 7 of the 20 necks, the rate of clinically occult disease being 35%, and 4 of them had been accurately graded by MR. There was one false-positive MR examination. The MR sensitivity was 57.1% and specificity 92.3%. CONCLUSION: MR may reveal metastatic lymph nodes in patients with no clinical evidence of metastasis. However, conventional MR techniques are not always sufficient for decision-making on surgery in cases of "N0 neck".     

Aggressive cutaneous squamous cell carcinoma of the head and neck in patients with chronic lymphocytic leukaemia

We describe multiple cutaneous squamous cell carcinomas of the head and neck in five patients with chronic lymphocytic leukaemia (CLL). When associated with CLL, cutaneous squamous cell carcinomata behave in a much more aggressive manner than otherwise expected. Four patients developed local recurrence after primary treatment. All five patients developed lymph node metastases containing squamous cell carcinoma. Three of five patients (60 per cent) had multiple primary lesions. Whereas the increased incidence of second cancers in CLL and notably of skin cancers is documented, little has been written to describe the aggressive behaviour of these tumours. It is important, when treating these patients, to be aware of the high tendency towards local recurrence and lymph node metastasis and to consider an aggressive management plan and careful follow-up.     

Six primary squamous cell carcinomas of the head and neck

Estrogens have a beneficial effect on atherosclerosis and osteoporosis after menopause, but their exact mechanism of action is still unknown. The aim of the present study was to investigate the effects of estradiol and its metabolites catechol estrogens on arachidonic acid metabolism in vitro. Estradiol had no effect on arachidonic acid metabolism up to 33 microM in A23187-stimulated human whole blood. All catechol estrogens (2-hydroxyestradiol, 2-hydroxyestrone, 4-hydroxyestradiol and 4-hydroxyestrone) had similar kinds of actions on arachidonic acid metabolism, being over ten times more potent inhibitors of leukotriene synthesis (IC50 values 0.044-0.16 microM) than thromboxane (IC50 values 0.99-2.1 microM) and prostaglandin E2 synthesis (IC50 values 0.84-5.5 microM). It is suggested that some of the protective actions of estrogens--e.g., on atherosclerosis and osteoporosis--may be related to the inhibition of leukotriene synthesis by catechol estrogens.     

Expression of multidrug resistance-associated protein (MRP) in head and neck squamous cell carcinoma

Vascular parkinsonism is thought to be a distinct parkinsonian syndrome associated with small deep infarcts and white matter lesions (WMLs). We studied the prevalence of parkinsonian features (bradykinesia, rigidity, tremor, and gait disorder) in relation to small deep or territorial infarcts and WMLs on computed tomography (CT) in 62 lacunar and 41 territorial stroke patients, at 3.0 (median) years of follow up. One or more parkinsonian signs were found in 36% of these patients; 11% clinically had parkinsonism. Parkinsonian signs were found more frequently in lacunar than in territorial stroke patients: bradykinesia in 45% and 7%, rigidity in 13% and 7%, tremor in 6% and 7%, and gait disorder in 16% and 7%, respectively. Patients with WMLs at study entry (n = 16) were compared with those without WMLs (n = 87): 56% and 25% had bradykinesia, 25% and 8% rigidity, 25% and 3% tremor, and 38% and 8% gait disorder, respectively. Regression analysis with adjusted odds ratios ([a]OR) showed that WMLs at study entry were associated with bradykinesia ([a]OR 8.0, 95% confidence interval [CI] 1.6-41.6), gait disorder ([a]OR 7.1, 95% CI 1.5-33.7), and tremor ([a]OR 7.0, 95% CI 1.2-40.3). Bradykinesia was associated with lacunar stroke at study entry ([a]OR 11.5, 95% CI 2.4-54.9). Thus, one third of our stroke patients had one or more parkinsonian signs, and 10% clinically had a parkinsonian syndrome that differed from Lewy body parkinsonism: infrequent resting tremor, but frequent gait disorder. Parkinsonian signs were associated with WMLs and lacunar stroke. Therefore, this study favors a distinct vascular parkinsonian syndrome.     

Analysis of p53 serum antibodies in patients with head and neck squamous cell carcinoma

BACKGROUND: Mutation of the p53 tumor suppressor gene (also known as TP53) often leads to the synthesis of p53 protein that has a longer than normal half-life. Mutant p53 protein that accumulates in tumor cell nuclei can be detected by means of immunohistochemical staining techniques. Serum antibodies directed against p53 protein (p53-Abs) have been detected in some cancer patients. PURPOSE: We assayed serum samples from 80 patients with head and neck squamous cell carcinoma (HNSCC) for the presence of p53-Abs, and we evaluated potential associations between the presence of these antibodies and other histopathologic and clinical features. METHODS: Serum was collected from each patient at the time of diagnosis. In addition, tumor biopsy specimens were obtained before the initiation of treatment. An enzyme-linked immunosorbent assay was used to detect p53-Abs. The accumulation of p53 protein in tumor cell nuclei was assessed immunohistochemically by use of the anti-p53 monoclonal antibody DO7. Patient treatment consisted of radiotherapy alone, primary chemotherapy followed by radiotherapy, or surgery and postoperative radiotherapy. Relapse-free and overall survival from the beginning of treatment were estimated by use of the Kaplan-Meier method; survival comparisons were made by use of the logrank statistic. Univariate and multivariate analyses were conducted to identify factors associated with survival. Reported P values are two-sided. RESULTS: Fifteen (18.8%) of the 80 patients had p53-Abs. Tumor cell nuclei in 43 (58.9%) of 73 assessable biopsy specimens exhibited strong p53 immunostaining. Patient treatment method and the accumulation of p53 protein in tumor cell nuclei were not associated with increased risks of relapse or death. In univariate analyses, advanced tumor stage (> T1 [TNM classification]) and the presence of p53-Abs were significantly associated with an increased risk of death (P for trend = .007 and P = .002, respectively), whereas advanced tumor stage, substantial regional lymph node involvement (> N1), and the presence of p53-Abs were associated with an increased risk of relapse (P for trend = .002, P = .02, and P < .0001, respectively). In multivariate analyses, advanced tumor stage and the presence of p53-Abs were significantly associated with increased risks of relapse (p for trend = .04 and P = .003, respectively) and death (P for trend = .04 and P = .03, respectively). At 2 years of follow-up, the overall survival proportion was 63% (95% confidence interval [CI] = 47%-80%) when no p53-Abs were detected compared with 29% (95% CI = 4%-54%) when p53-Abs were detected. Relapse-free survival at 2 years was 62% (95% CI = 49%-76%) if no p53-Abs were detected compared with 13% (95% CI = 0%-31%) if p53-Abs were detected. CONCLUSIONS AND IMPLICATIONS: The proportion of patients with HNSCC who have serum p53-Abs is smaller than that of patients exhibiting tumor cell accumulation of p53 protein. The presence of p53-Abs is significantly associated with increased risks of relapse and death.     

Radiotherapy and concurrent chemotherapy for the treatment of locally advanced head and neck squamous cell carcinoma

PURPOSE: To determine whether combination 5-fluorouracil, cisplatin, and interferon alfa, an active regimen in advanced esophageal cancer, is efficacious as induction therapy before esophagectomy. MATERIALS AND METHODS: Forty-four patients with potentially resectable esophageal/gastroesophageal junction adenocarcinoma or squamous cell carcinoma were entered into a phase I/II study of this chemotherapeutic regimen and concurrent external-beam radiotherapy before resection. The initial 16 patients were treated with prolonged-infusion 5-fluorouracil (300 mg/m2 on days 1 to 28), cisplatin (20 mg/m2 on days 1 to 5 and 24 to 28), interferon alfa (3 x 10(6) U/m2 intravenously on days 1 to 5 and 24 to 28; subcutaneous injection every other day on days 6 to 23), and radiation (4000 cGy). The subsequent 28 patients were treated over 21 days with two modifications: dose escalation of 5-fluorouracil (250 to 350 mg/m2) and double-fractionated radiotherapy to a total dose of 4500 cGy. RESULTS: Forty-one patients completed chemoradiotherapy and were evaluable for toxicity. Adverse events were substantial but tolerable, and most toxic episodes were hematologic and gastrointestinal. Three patients died, and one patient had progressive disease before resection. Of the 37 patients eligible for curative resection, 36 had all gross tumor removed. Thirty-three (80%) patients had a major pathologic response: 10 (24%) with no residual tumor and 23 with only microscopic residual tumor. Median survival for all patients was 27 months and for responders was 36 months. CONCLUSIONS: This combination regimen is active but yields results similar to those of other chemoradiotherapy phase II trials; therefore, the contribution of interferon alfa to treatment efficacy remains uncertain. The true worth of preoperative chemoradiotherapy is unknown pending results of phase III trials.     

The effect of lidocaine on growth of cells of head and neck squamous cell carcinoma

The relation between 21 absolute body dimensions as well as 20 anthropometric indices and the length as well as the regularity of the menstrual cycle have been investigated in 156 patients of the hormone ambulance of the I. Universit?ts-Frauenklinik in Vienna. It turned out, that the length as well as the regularity of the menstrual cycle significantly negatively with the amount of the subcutaneous fat tissue. With an increasing amount of adipose tissue, the cycle became shorter and more regular. The importance of the subcutaneous fat tissue as a secondary hormonal gland has been discussed as one cause for these significant connections. Regarding the length- and height dimensions and the menstrual cycle patterns, no statistically significantly relationship could be observed between these two trait system. This is also true for the relationship between body built and the bleeding duration.