Basic fibroblast growth factor in serum and urine of patients with head and neck cancer

Between 1996 and 1997 serum and urine levels of basic fibroblast growth factor (b-FGF) in patients with head and neck cancer were measured to answer the following questions: i) Are increased levels of b-FGF in serum and urine detectable in patients with malignant head and neck tumors? ii) Do these parameters correlate with tumor stage and differentiation of tumors? iii) Is there an association between growth behaviour (local or metastatic growth) and b-FGF levels in serum and/or urine? Eighty-nine patients with head and neck cancer as well as 45 patients with diseases unrelated to cancer were investigated. Detectable levels of b-FGF were found in the serum and urine of patients with malignant head and neck tumors. In addition, there was a significant correlation between tumor size and b-FGF levels in either serum or urine. No association of b-FGF concentrations with degree of histologic differentiation and tumor growth behaviour was observed. The results of this study demonstrate that b-FGF levels are elevated in serum and urine of patients with head and neck cancer. These findings suggest an involvement of b-FGF in the formation of solid tumors.     

Neuralgic amyotrophy or an isolated lesion of the anterior interosseal nerve?]

OBJECTIVE: Considerable evidence exists to suggest that tumor hypoxia results in radioresistance. Historically, it has been difficult to assess tumor oxygen tension levels reliably. These levels can now be assessed in head and neck malignancies using the Eppendorf pO2 histograph, which uses a fine-needle electrode and a computerized micromanipulator. This technology was used to compare the pretreatment tumor oxygen tension level in lymph node metastases of patients with head and neck cancer to measurements taken during nonsurgical treatment after a partial response had been achieved. STUDY DESIGN: Prospective study. METHODS: Oxygen tension levels were measured in the cervical lymph nodes of 10 patients with biopsy-proven head and neck squamous cell carcinoma and cervical metastases who were being treated with nonsurgical management. These levels were obtained using the Eppendorf pO2 histograph system. Measurements were taken before the start of treatment and were repeated when the size of the cervical metastatic node had decreased by 50%. Normal subcutaneous tissue was measured during the same session. The mean and median pO2 levels, as well as the percentage of measurements with pO2 less than 5 mm Hg were determined. RESULTS: A mean of 72.6 measurements per session was taken from each lymph node. The median tumor pO2 measurement fell from a mean (+/-SD) of 13.9+/-8.0 mm Hg to 7.3+/-9.9 mm Hg. Even more dramatic, however, was the substantial increase in the percentage of values less than 5 mm Hg, a rise from 29% to 52%. CONCLUSIONS: While there is variability both in the pretreatment oxygenation of head and neck cervical metastases and in the change in tumor oxygen tension during treatment, there appears to be a decrease in the overall oxygenation of the tumors. The dramatic increase in very low oxygen measurements may reflect selective survival of radioresistant or chemoresistant hypoxic tumor cells. Cells at the very low level would be expected to be radiobiologically hypoxic (resistant to radiation-induced cell kill).     

The potent antioxidant activity of the vitamin K cycle in microsomal lipid peroxidation

OBJECTIVE: To determine the outcomes of patients with neurotropic cutaneous tumors of the head and neck. DESIGN: A retrospective review was conducted of 7852 charts of patients who underwent micrographically controlled excisions of skin cancers of the head and neck between 1984 and 1995, identifying neurotropic tumors and the outcomes of their treatments. SETTING: Tertiary care center (university hospital). PATIENTS: Thirty-seven patients with neurotropic tumors were identified (and confirmed by secondary histological review), constituting 0.47% of all patients. The median age at presentation was 68 years and all except an albino were white. Nine patients had basal cell carcinomas and 28 had squamous cell carcinomas. Twenty-five patients (69%) were referred after at least 1 prior excision was performed a median of 16 months previously. INTERVENTION: All patients underwent micrographic mapping and excision of the cutaneous portion of the tumor. As necessitated by tumor spread, additional soft tissue, skull base, and/or intracranial surgery and postoperative irradiation were also conducted. MAIN OUTCOME MEASURES: Thirty-four patients (3 patients were unavailable for follow-up) were assessed by physician examination a minimum of 19 months after treatment (median, 33 months). RESULTS: Of 25 patients with extracranial disease only, 19 had no evidence of disease during follow-up and 1 died of intercurrent disease at 20 months without evidence of tumor persistence. Of the 9 patients with intracranial neurotropic tumors at the time of presentation, 1 remained with no evidence of disease, 1 died of intercurrent disease at 21 months without evidence of tumor persistence, and the other 7 either died of or are living with an intracranial tumor. CONCLUSIONS: Micrographic tissue mapping to detect and then encompass neurotropic cutaneous malignancies, along with conventional surgery for deeper tumor invasions and irradiation in selected cases, was successful in 19 patients (76%) with an extracranial tumor. For those with neurotropic tumors approaching or penetrating the skull base, the prognosis was poor regardless of therapy method.     

Fibroblasts prevent apoptosis of IL-2-deprived T cells without inducing proliferation: a selective effect on Bcl-XL expression

Tumour hypoxia is well recognised as a major factor contributing to radioresistance. This article examines the role of hypoxia in influencing the treatment outcome following radiotherapy (RT), and reviews the rationale and results of clinical trials that utilise hypoxic sensitizers or cytotoxins in the treatment of head and neck carcinoma. Histologic evidence for tumour hypoxia in human neoplasms was first reported in 1955. Since then, direct measurement by microelectrodes has revealed heterogeneity in intratumoural oxygen concentrations, and low oxygen concentrations are associated with poor local-regional control by RT. These findings coupled with the result of nuclear imaging studies employing radiolabelled imidazoles, provide strong evidence for the existence of tumour hypoxia which influences RT treatment outcome. Hyperbaric oxygen (HBO) trials for head and neck cancer, conducted in the early 1970s, demonstrated that HBO improved local control and survival rates in patients with head and neck cancer receiving radiotherapy (RT). Since the mid-1970s, clinical research in overcoming tumour hypoxia was mainly centred on the use of nitro-imidazoles as hypoxic cell sensitizers. However, the results from several major clinical trials remain inconclusive. Specifically, the Radiation Therapy Oncology Group (RTOG) misonidazole head and neck trial (298 patients) showed no benefit. The Danish misonidazole trial (626 patients) showed no overall benefit, however positive results were observed in a subgroup (304 pharyngeal cancer patients). Although the European Organisation for Research and Teaching of Cancer (EORTC) misonidazole trial with hyperfractionated RT showed no benefit, the Danish nimorazole trial demonstrated an overall benefit in survival as well as local control. The European etanidazole (ETA) trial (374 patients) showed no advantage of adding the drug to RT. The RTOG ETA trial (504 patients) showed no global benefit. However, positive results were observed in a subset of patients with early nodal disease (197 patients). In addition, a recent meta-analysis by Overgaard, utilising pooled results in the literature demonstrated that modification of tumour hypoxia significantly improved local-regional control in head and neck cancers with an odds ratio of 1.23 (95% confidence limits 1.09 to 1.37). Hypoxic cytotoxins, such as tirapazamine, represent a novel approach in overcoming radioresistant hypoxic cells. Tirapazamine is a bioreductive agent which, by undergoing one electron reduction in hypoxic conditions, forms cytotoxic free radicals that produce DNA strand breaks causing cell death. In vitro and in vivo laboratory studies demonstrate that tirapazamine is 40 to 150 times more toxic to cells under hypoxic conditions as compared to oxygenated conditions and that tirapazamine is superior to ETA in enhancing fractionated irradiation in mouse SCCVII and other tumour types with an enhancement ratio of 1.5 to 3.0. Phase I studies demonstrated that therapeutic doses of tirapazamine can be given safely. A multi-institutional phase II trial using tirapazamine with concurrent RT for head and neck cancer is now in progress.     

Inhibition of human squamous cell carcinoma growth in vivo by epidermal growth factor receptor antisense RNA transcribed from the U6 promoter

BACKGROUND: Squamous cell carcinomas of the head and neck (SCCHN), unlike normal mucosal squamous epithelial cells, overexpress epidermal growth factor receptor (EGFR) messenger RNA and protein. EGFR protein is required to sustain the proliferation of SCCHN cells in vitro. To determine whether EGFR expression contributes to tumor growth, we investigated the effect of suppressing EGFR expression in tumor xenografts through in situ expression of antisense oligonucleotides. METHODS: Intratumoral cationic liposome-mediated gene transfer was used to deliver plasmids capable of expressing sense or antisense EGFR sequences into human head and neck tumors, which were grown as subcutaneous xenografts in nude mice. The oligonucleotides were expressed under the control of the U6 RNA promoter. RESULTS: Direct inoculation of the EGFR antisense (but not the corresponding sense) plasmid construct into established SCCHN xenografts resulted in inhibition of tumor growth, suppression of EGFR protein expression, and an increased rate of apoptosis (programmed cell death). Sustained antitumor effects were observed for up to 2 weeks after the treatments were discontinued. CONCLUSION: These results suggest that interference with EGFR expression, using an antisense-based gene therapy approach, may be an effective means of treating EGFR-overexpressing tumors, including SCCHN.     

Sequestration of the lung arising from the circumflex coronary artery

The patterns of macroscopic growth of 20 first generation human tumor xenografts (16 renal cell carcinomas and 4 squamous cell carcinomas of the head and neck region) were studied with the recursion formula of the Gompertz function. This method enables the characterization of each tumor growth pattern by two parameters: (i) parameter a, which correlates with the starting growth rate of the tumor and (ii) parameter b, which is a measure of the intensity of growth deceleration as a function of tumor growth. A statistically significant prediction of the establishment of a xeno-transplantation line after serial subpassaging (in 9/20 tumors) according to the characteristics of first passage growth curves (p<0. 01) is reported. Especially parameter b, the value of the growth deceleration, highly correlates with serial growth: tumors showing less growth deceleration (higher b-values) during first passage more frequently develop into transplantation lines. On the contrary line development could not be predicted on the basis of the a-values of the first passage growth curves alone (p=0.137). This observation adds to the accumulating evidence, that the process of tumor growth deceleration is a pivotal parameter of tumor biology. Moreover, the present evaluation substantially reduces the time needed to assay serial growth of tumor xenografts for prognostic purposes making this assay potentially more attractive for clinical use.     

Genetic predisposition and radiation sensitivity of tumors

BACKGROUND: Studies on normal tissue radiation sensitivity have demonstrated profound differences of individual sensitivities. A number of genetic syndromes associated with abnormal radiation sensitivity have been described. Significant differences have also been detected in persons without known genetic disorders. The question arises as to whether tumors originating from normal tissues with abnormal radiation sensitivity share this abnormal sensitivity and as to whether a general correlation between normal tissue sensitivity and tumor tissue sensitivity can be substantiated. METHODS: Experimental and clinical data derived from own investigations and an extensive review of the literature was used to answer the question. RESULTS: Experimental studies on normal and tumor tissues of SCID-and C3H-mice demonstrated that the 2.7-fold enhanced radiation sensitivity of SCID normal tissues is also found in SCID tumors. Clinical investigations on cervical carcinoma and breast cancer patients revealed higher local control rates in patients with more pronounced acute side effects. A weak trend towards the same relationship was found in head and neck cancer patients. Case reports on unusually severe acute radiation side effects or unexpected tumor remissions as well as few reports on radiotherapy in ataxia telangiectasia (AT) patients suggest a correlation between normal- and tumor-tissue radiation sensitivity. Studies on fibroblasts and tumor cells from the same patient support this hypothesis in soft tissue sarcoma patients, but do not so for head and neck cancer patients. Tumor cells exhibit a considerably higher variation of radiation sensitivities than normal tissue cells. CONCLUSIONS: Experimental and clinical data are compatible with the hypothesis that normal tissue radiation sensitivity predicts for tumor tissue sensitivity. However, in view of the larger heterogeneity of tumor cell radiation sensitivity as compared to normal tissue radiation sensitivity, the development of a clinically useful predictive test for tumor sensitivity based on normal cell sensitivity appears to be unrealistic.     

Cytokinetic effects of cisplatin on diverse human head and neck carcinomas in vitro: dependence on the tumor sensitivity to cisplatin

Studies performed with xenografted human head and neck carcinomas in vivo have demonstrated that the cytokinetic phenomena occurring under the influence of cisplatin closely correlate with the response of the tumors to therapy. The present paper analyses whether this correlation also exists in vitro. Four human head and neck carcinoma cell lines showing different degrees of sensitivity to cisplatin, as determined by the trypan blue exclusion assay, were investigated by flow cytometry at various intervals after administration of cisplatin. Early cell-cycle blockades in the S phase always reflected a high degree of cytostatic potency of cisplatin and were usually succeeded by a pronounced inhibition of tumor cell proliferation and a reduction of cell viability. In the case of a minimal response to therapy and in untreated control cultures of all four tumor lines, the relative number of S-phase cells continuously diminished during the observation period. These findings point to the S-phase blockade as the crucial cytokinetic effect of cisplatin preceding relevant growth reductions. This knowledge might support the development of a drug-response assay that could predict the sensitivity of individual patient tumors in vitro before the beginning of clinical cancer chemotherapy.     

Expression of the double-stranded RNA-dependent protein kinase (p68) in squamous cell carcinoma of the head and neck region

OBJECTIVE: p68 is an interferon-inducible protein kinase that is believed to be an important factor in the regulation of both viral and cellular protein synthesis. We have previously shown that p68 expression correlates with differentiation in a variety of tumors, including squamous cell carcinoma of the head and neck region. The current study aims to identify the prognostic significance of p68 expression in squamous cell carcinoma of the head and neck. DESIGN: Archival material from a cohort of 75 patients with primary squamous carcinomas of the head and neck was immunostained for p68 with the monoclonal antibody TJ4C4. Overall scores for p68 expression were tabulated based on staining intensity and percentage of immunoreactive tumor cells. Clinical information including tumor grade, stage, site, treatment, disease-free, and total survival was tabulated and compared by p68 expression group. SETTING: Veterans Administration Lakeside Medical Center and outpatient clinics (Northwestern University and Veterans Administration Lakeside Medical Center, Chicago, Ill). PATIENTS: Seventy-five consecutive patients with primary squamous cell carcinoma of the head and neck (excluding the esophagus), with tissue blocks available for study, a known primary site, no history of prior carcinoma, and demographic and follow-up information available. MAIN OUTCOME MEASURED: Disease-free and overall survival rates. RESULTS: While there was a wide range of outcomes within each group, as a group, high levels of p68 expression correlated with a lower incidence of recurrent or residual disease and longer disease-free and total survival times compared with groups with lower levels of p68 expression. These differences could not be explained on differences in patient age, tumor grade, and TNM stage. CONCLUSIONS: High-level p68 expression is associated with prolonged disease-free and overall survival in a series of patients with squamous cell carcinoma of the head and neck region. Additional study is needed to monitor changes in p68 expression with treatment or tumor progression.     

Dysregulated cyclin D1 expression early in head and neck tumorigenesis: in vivo evidence for an association with subsequent gene amplification

Cyclin D1 proto-oncogene is a key regulator of the mammalian cell-cycle acting at the restriction point in late G1. Amplification of the cyclin D1 locus, located on chromosome 11q13, as well as cyclin D1 protein overexpression have been reported in several human malignancies. The purpose of this study was to evaluate cyclin D1 gene copy status and protein expression during the multistep process of head and neck tumorigenesis, using a combination of fluorescence in situ hybridization and immunohistochemistry techniques. From 29 selected patients presenting with head and neck squamous carcinoma and whose tumor cytospins had been previously screened for presence (16 cases) or absence (13 cases) of amplification at the 11q13 band, we analysed 46 paraffin-embedded tissue specimens that demonstrated, besides the primary tumor, the presence of contiguous adjacent normal tissue and/or premalignant lesions. Of the 16 amplified cases, nine demonstrated a continuous progression from premalignant to invasive carcinoma and seven (77.7%) of these cases showed cyclin D1 gene amplification in premalignant lesions prior to development of invasive carcinoma. Increased cyclin D1 protein expression was observed in all 16 amplified tumors and five of the 13 (38.4%) non-amplified tumors. Interestingly, dysregulated cyclin D1 expression was also found in the premalignant lesions adjacent to all 16 amplified tumors, and it appeared to precede cyclin D1 gene amplification. In contrast no dysregulated expression was detected in the premalignant lesions of the non-amplified tumors. In conclusion, these findings provide strong evidence for early dysregulation of cyclin D1 expression during the tumorigenesis process and suggest that dysregulated increased expression precedes and possibly enables gene amplification.     

P53 overexpression in head and neck carcinoma and radiotherapy results

PURPOSE: P53 gene mutations are the common genetic changes encountered in human cancers, and there is extensive evidence that the P53 status may determine tumor response to therapy. This study was carried out to investigate whether there is any correlation between accumulation (overexpression) of P53 protein and poor prognosis in patients with head and neck carcinomas treated with radical radiotherapy. METHODS AND MATERIALS: Seventy-nine patients with head and neck carcinomas who were diagnosed and treated in 1989-90 with curative radiotherapy were studied retrospectively. Paraffin sections from archival material were studied using immunohistochemical staining (IHC) with mouse monoclonal antibodies (D0-7) to human P53 protein. Univariate and multivariate analysis of loco-regional tumor control and patient survival were performed on possible prognostic factors. RESULTS: Forty-two (53%) patients showed positive IHC staining in their tumors. Fifty-three percent of the laryngeal, 64% of the oropharyngeal, and 43% of the oral cavity carcinomas showed P53 overexpression. All tumor specimens with vascular, lymphatic, and/or sarcolemmal invasion showed P53 overexpression. The proportion of tumor-stained nuclei was higher in the poorly differentiated than in the well and moderately differentiated tumors (p < 0.05), but there was no correlation with the patient overall or disease-free 5-year actuarial survival. There was no difference in the 5-year actuarial survival and disease-free survival between patients with P53 immunostaining in their tumors and those with no immunostaining (59% vs. 65% and 57% vs. 51%, respectively). The TNM tumor stage was the most significant prognostic factor with 5-year actuarial survival of 87% for early and 14% for late stages (p < 0.0001). There was a significant correlation between immunostaining and history of smoking (p = 0.02). CONCLUSION: The data demonstrate that the P53 accumulation as detected by immunohistochemical staining in a group of head and neck carcinomas was not predictive of patient's poor survival or disease-free survival. Multivariate statistical analysis showed that the TNM tumor stage was the only significant prognostic factor. There was a significant association between P53 accumulation and smoking.     

Role of sialoglycan structures for the function of the epidermal growth factor receptor and the in vitro proliferation of head and neck cancer

Squamous cell carcinomas of the head and neck have been found to show a high expression of the receptor for epidermal growth factor (EGF). This overexpression of the receptor has been associated with malignant transformation of cells, although there is still debate as to what extent this receptor takes part in the proliferation of malignant cells and which function it fulfills. The factors which determine receptor-ligand interaction are also not clearly defined. That the extracellular domain of the EGF receptor carries carbohydrate or sialoglycan structures might be important for function of the receptor. Since tumor specific enzymes can possibly alter such structures, it was the aim of our study to investigate the role of these structures on the EGF receptor during the proliferation of head and neck carcinomas. We used the human laryngeal squamous carcinoma cell line HLaC 79 and altered, for the first time, specific glycan structures with sialidase alpha-2,3 and alpha-2,6, causing desialylation. Changes were also produced by endo-beta-galactosidase and sialyltransferase. Findings were monitored by labeling with bromo-deoxyuridine. To determine receptor affinity, 125I-labeled EGF was employed. Results showed that both cell proliferation and receptor affinity depended on the level of sialylation of the receptor carbohydrate side chains. Desialylation led to a statistically significant reduction of tumor cell proliferation to 65 +/- 33% (P < 0.01), while receptor affinity decreased to 70 +/- 26% (P < 0.01). The importance of EGF receptor for the proliferation of malignant cells seems to depend on the level of sialylation of glycan structures on receptor protein. A release of enzymes by tumor cells may then produce auto-control of tumor proliferation on its own.     

Cell, tissue and organ culture as in vitro models to study the biology of squamous cell carcinomas of the head and neck

In vitro models are currently being used to study head and neck squamous cell carcinoma (HNSCC). Several hundred HNSCC cell lines have been established by various investigators and used to study a broad spectrum of questions related to head and neck cancer. The head and neck model with respect to multistage carcinogenesis is now complete. Several techniques exist for the culture of normal epithelial cells from the upper aerodigestive tract (UADT). The biology of these UADT cells (oral cavity, oropharynx, hypopharynx and larynx) is being studied. Successful culture of premalignant lesions (dysplastic mucosa, leukoplakia, erythroplakia) has resulted in establishment of a limited number of premalignant cell lines and cell cultures. HPV infection of normal oral epithelial cells for immortalization (approximately premalignant cells) coupled with transformation with carcinogens (malignant cells) has established an experimental model for progression. Two in vivo models for oral carcinogenesis, the 7,12 dimethylbenz(a)anthracene-induced hamster cheek pouch model and the 4-nitroquinoline-N-oxide rat oral model, have been established in culture. Thus, multistage carcinogenesis models have been established from both human tissues and animal models and include cultures of normal, premalignant and malignant cells. Culture techniques for growing dissociated primary tumor cells for short term experimental analysis are being used. The culture of normal or tumor tissue as organ/explant cultures allows for the maintenance of normal cell-cell and cell-matrix interaction, but limits experimentation since these cultures cannot be propagated. Several three dimensional model systems are being used to obtain this histological complexity but allow for experimentation. The ability to culture normal, premalignant and malignant cells coupled with the use of a variety of culture techniques, should allow for the continued growth and experimentation in head and neck cancer research.     

Hyperbaric oxygen for the management of radionecrosis of bone and cartilage

OBJECTIVES: To review the use of hyperbaric oxygen in the management of radionecrosis of the head and neck. STUDY DESIGN: A retrospective analysis of patients utilizing chart review and telephone interviews. All patients diagnosed with osteoradionecrosis and chondroradionecrosis of the head and neck and treated with hyperbaric oxygen at the University of Virginia are included. METHODS: Demographics, pretreatment data, and precipitating events were recorded. Outcomes were evaluated using a grading scale of symptomatology and physical examination as determined by the patient and physician. RESULTS: Sixteen patients with osteoradionecrosis and five with chondroradionecrosis were reviewed. All patients showed clinical improvement with decreased pain following HBO therapy. None of the patients with chondroradionecrosis required laryngectomies, and two of the four who were tracheotomy dependent were successfully decannulated. The patient and physician grading scores demonstrated moderate to significant improvement in both groups following therapy. CONCLUSION: The successful use of hyperbaric oxygen for the management of radionecrosis of the head and neck is supported. The unusual prevalence of chondroradionecrosis may be an early reflection of changes in treatment protocols for patients with head and neck cancer.     

The radiographic evaluation of sinonasal tumors: an overview

It is axiomatic that advances in head and neck imaging improve our understanding of head and neck diseases. Dramatic improvements in radiologic imaging in recent years have, as a corollary, dramatically improved our understanding of sinonasal tumors. Older techniques such as plain film radiography and multidirectional tomography poorly delineate normal anatomy and pathologic changes in the craniofacial region. Modern imaging modalities depict sinonasal tumors and their metastases in detail, yielding information that allows treatment planning to proceed rationally. The radiologic examination is commonly employed as a precise "map" for implementation of therapy, and imaging studies are essential in the follow-up evaluation for tumor residual or recurrence. This article provides an overview of the current contributions made by head and neck radiology to the understanding and clinical management of sinonasal tumors.     

Plasmacytomas of the head and neck

Plasmacytomas are rare tumors that often appear in the head and neck region and are characterized by a monoclonal proliferation of plasma cells. On both clinical presentation and pathologic examination these tumors may be confused with more common tumors of the head and neck. The purpose of this article is to review our experience with these rare neoplasms, with emphasis on clinical, pathologic, and therapeutic features. On retrospective chart review, we identified 20 patients with the diagnosis of plasmacytoma of the head and neck region at the Cleveland Clinic Foundation between 1976 and 1993. Records were reviewed with regard to initial symptoms, location of the neoplasm, diagnostic evaluation, treatment modalities, and survival. Of the 20 cases we identified, the tumor arose in the sinonasal/nasopharyngeal region in 11 (55%). Two cases (10%) represented medullary plasmacytomas, arising in the clavicle and presenting as supraclavicular masses. The mean follow-up was 60.2 months (range 6 to 131 months). In 15 of the 20 cases, immunohistochemistry staining for immunoglobulin light chain production was conducted. One of the two cases (50%) classified as medullary plasmacytoma demonstrated conversion to multiple myeloma, whereas only 2 of 18 cases of extramedullary plasmacytoma (11%) converted to multiple myeloma. The primary modality of treatment was radiation therapy with typical doses of 4500 to 6000 cGy. Kaplan-Meier survival estimates demonstrated 95% survival at 1 year, 82% survival at 5 years, and 10-year estimated survival of 72%. Plasmacytomas of the head and neck region are rare and on initial evaluation must be distinguished from multiple myeloma. The diagnostic evaluation includes appropriate radiologic and pathologic studies including immunohistochemistry. Despite the typical presentation as a locally destructive tumor, plasmacytomas are highly radiosensitive, and 70% to 80% survival may be obtained with the use of radiotherapy. Patients with plasmacytomas require long-term follow-up to detect conversion to multiple myeloma.     

The "Nobel": Prize and swindle. The betrayed testament

Human glutathione S-transferase pi (GST-pi) may serve as a useful tumor marker because of the high frequency with which it is found in elevated levels in several tumor types. To determine whether GST-pi is useful as an indicator for cancers of the head and neck, expression of GST-pi mRNA was investigated by Northern analysis in this tumor type. Overexpression of GST-pi mRNA was detected in 9 of 36 (25%) primary head and neck squamous cell carcinomas (HNSCCs). When Southern blot analysis was used to examine the relationship between overexpression and amplification of the GST-pi gene, only 3 of 36 tumors (8%) showed GST-pi gene amplification. Thus, gene amplification is not critical to GST-pi mRNA overexpression in HNSCCs. Moderately and poorly differentiated HNSCCs tended to manifest elevated GST-pi mRNA compared with well differentiated tumors (30% for moderately and poorly differentiated tumors versus none of the well differentiated tumors examined). However, there was no significant correlation between GST-% mRNA overexpression and clinical stage, T stage (tumor size), N stage (neck nodal status), pathological nodes, or patient survival.     

Inhibition of tumor growth and invasion by a four-kringle antagonist (HGF/NK4) for hepatocyte growth factor

Invasion of various carcinoma cells follows their interaction with stromal cells. Hepatocyte growth factor (HGF), four-kringle-containing growth factor, is a mesenchymal or stromal-derived mediator which affects the growth and the invasiveness of carcinoma cells. We now have evidence that a four-kringle-containing antagonist for HGF, HGF/NK4 inhibits invasion of tumors in vivo, as well as in vitro. HGF/NK4 competitively inhibited the binding of HGF to Met/ HGF receptors on GB-d1 human gallbladder carcinoma cells. HGF induced invasion of the cells through Matrigel basement membrane components and into collagen gels, but HGF-induced invasion was inhibited by HGF/NK4. Invasion of GB-d1 cells was induced by co-cultivation with stromal fibroblasts, which mimics tumor-stromal interaction, but it was almost completely suppressed by HGF/NK4. Likewise, invasive growth induced by HGF in collagen gels in GB-dl cells, HuCC-T1 human cholangiocarcinoma cells, and ME-180 human uterus cervical carcinoma cells was also strongly inhibited by HGF/NK4. When GB-d1 cells were implanted subcutaneously into nude mouse, tumor cells invaded muscular tissue, but the infusion of HGF/NK4 inhibited this invasion. Furthermore, HGF/NK4 increased apoptotic cell death of GB-d1 cells and inhibited tumor growth in vivo. These results indicate that HGF/ NK4 may inhibit growth and invasion of carcinoma cells, as mediated by HGF during tumor-stromal interactions. We propose that there is a unique therapeutic potential for HGF/NK4 to prevent tumor invasion and perhaps even metastasis.     

Acute induction of interleukin-6 and biphasic changes of serum complement C3 by carrageenan in mice

Oat cell carcinoma is rarely diagnosed in the head and neck and can be primary or secondary. Primary tumors arise from amine precursor uptake and decarboxylation cells which are found throughout the head and neck. Secondary deposits metastasize most commonly from the lungs. We report a 64-year-old woman with a known pancreatic oat cell carcinoma who came to the ENT Department with dysphagia. On examination, a lesion was seen at the base of the tongue and was histologically an oat cell carcinoma. No treatment was administered and the patient died one month after discharge. This report highlights the difficulty in determining the primary site when a rare tumor metastasizes to the head and neck and no autopsy findings are obtained. To our knowledge, oat cell carcinoma of the tongue has not been previously reported.