Biomedical subjects

G J Petruzzelli

Publications and source records attributed to G J Petruzzelli.

At least 19 recordsLinked to original sources

PubMed2001

Human squamous cell carcinomas of the head and neck chemoattract immune suppressive CD34(+) progenitor cells.

CD34(+) progenitor cells have previously been shown to be mobilized in patients with squamous cell carcinoma of the head and neck (HNSCC). The present study showed that these CD34(+) cells inhibit the capacity of intratumoral lymphoid cells to become activated in response to stimulation through the TCR/CD3 complex. The mechanisms that could lead to the accumulation of CD34(+) cells within the tumor tissue were assessed. This was accomplished through in vitro studies that determined if HNSCC produce soluble factors that chemoattract CD34(+) cells. The migration of cord blood CD34(+) cells, which were used as a readily available source of progenitor cells, was stimulated by products derived from HNSCC explants and primary HNSCC cultures. This stimulated migration was due to chemotaxis because it was dependent on an increasing gradient of HNSCC-derived products. CD34(+) cells that were isolated from the peripheral blood of HNSCC patients were similarly chemoattracted to the HNSCC-derived products. The majority of the chemotactic activity produced by HNSCC could be attributed to vascular endothelial cell growth factor (VEGF). These studies indicate that HNSCC can chemoattract immune inhibitory CD34(+) progenitor cells through their production of VEGF.

Antigens, CD34↗

PubMed2001

Carotid-cavernous fistulas: pathogenesis and routes of approach to endovascular treatment.

The etiology, classification, clinical presentation, complications, and intravascular routes to image and treat carotid-cavernous fistulas percutaneously are described. Endoarterial and transvenous approaches (through the jugular, inferior petrosal, or cavernous veins) are discussed in relation to the etiology, size, and characteristics of the fistulas, as well as in relation to the planned therapeutic approach and its possible complications. Possible outcomes, with particular attention to the internal carotid circulation, side effects, and complications also are discussed in relation to etiology and type of fistula. Four exemplary cases are presented.

Case Reports↗

PubMed2001

Patterns of spread in recurrent head and neck squamous cell carcinoma.

OBJECTIVE: To examine the pattern of spread regarding recurrent disease in primary head and neck squamous cell carcinoma. STUDY DESIGN AND SETTING: A retrospective study reviewed 128 patients who underwent primary tumor resection and postoperative radiation and/or chemoradiation for squamous cell carcinoma at Loyola University Medical Center from July 1993 to August 1998. Patterns of spread of recurrent disease were grouped according to site of recurrence and compared with the histopathology. RESULTS: Of 128 patients, 40 (32%) had recurrent disease, 22 (17%) died without disease, and 66 (51%) are disease free. Although the recurrences in patients who were N0 were primarily local-regional (8/11), the majority of recurrences in patients that were N+ with extracapsular nodal spread involved distant sites (18/24); 17/18 involved metastasis to the lung. SIGNIFICANCE: This study gives the first report at our institution of patterns of spread in recurrent head and neck squamous cell cancer and compares these patterns within subgroups of patients based on the extent of neck disease at the time of primary surgical resection. CONCLUSION: Not only was there a higher rate of recurrent disease in patients with extracapsular nodal spread, there was a much higher involvement of distant metastatic sites as opposed to local-regional recurrence more often seen with the N0 neck. The most common site of distant metastasis was the lung.

Carcinoma, Squamous Cell↗

PubMed2001

Increased levels of immune inhibitory CD34+ progenitor cells in the peripheral blood of patients with node positive head and neck squamous cell carcinomas and the ability of these CD34+ cells to differentiate into immune stimulatory dendritic cells.

OBJECTIVES: This study determined whether mobilization of immune inhibitory CD34+ cells by head and neck squamous cell carcinomas (HNSCC) is most prominent in patients who are node positive and whether these CD34+ cells could differentiate into immune stimulatory dendritic cells. STUDY DESIGN AND SETTING: Peripheral blood from patients with head and neck cancer was used to measure the frequency of CD34+ cells and their capacity to differentiate into immune stimulatory dendritic cells. RESULTS: This study demonstrated that increased CD34+ cell levels were most prominent in patients who were node positive and patients with recurrent disease. These CD34+ cells differentiated into dendritic cells that were able to present tetanus toxoid to autologous T-cells. CONCLUSIONS: Immune suppressive CD34+ cells that are prominent in patients with HNSCC who are node positive are able to develop into immune stimulatory dendritic cells. SIGNIFICANCE: Differentiation of tumor-mobilized CD34+ cells into dendritic cells may be an immunotherapeutic approach to stimulate antitumor reactivity.

Antigen Presentation↗

PubMed2001

Primary malignant melanoma of the larynx.

Primary malignant melanoma of the larynx is a rare clinical entity. Only 53 cases have been reported in the medical literature to date. This report describes a case of primary malignant melanoma arising in the larynx and diagnosed by histologic examination of an excisional biopsy specimen. The patient was a 53-year-old man with a history of smoking and hoarseness. There was no clinical evidence of other primary malignant melanocytic lesions. Microscopically, the tumor consisted of polygonal-epithelioid cells admixed with more elongated, spindle-shaped cells. The majority of the cells demonstrated dark brown cytoplasmic and nuclear melanin. Marked pleomorphism and abnormal mitoses were also identified. Despite significant ulceration and disruption of the epithelium, in situ malignant melanocytes were recognized within the remaining portion of the epithelium. Immunohistochemical studies were positive for S100, HMB-45, and vimentin, while cytokeratin and iron stains were negative. Based on the clinical and histologic findings, a diagnosis of primary malignant melanoma of the larynx was established.

Antigens, Neoplasm↗

PubMed2000

Frameless stereotactic localization in cranial base surgery.

Mastery of the three-dimensional anatomic relationships of the cranial base/paranasal sinuses is required to reduce the incidence of iatrogenic surgical complications, facilitate complete tumor extirpation, and enhance functional outcomes. Real-time intraoperative localization technology is one method available to assist the cranial base surgeon. We report our institutional experience with the StealthStationtrade mark treatment guidance platform. Eighty-eight consecutive patients with pathology of the cranial base/paranasal sinuses were operated on with the aid of real-time frameless stereotactic localization. Preoperative image data sets were acquired with either CT or MRI scans. Patient demographics, accuracy of the data sets, surgical approaches, pathology, complications, and further applications of this technology are presented. Procedures were performed on 47 women and 41 men ranging in age from 6 to 85 years. In these 88 procedures, 44 MRI and 44 CT scans with a mean accuracy of 1.57 and 1.23 mm, respectively, were used. Approaches to the cranial base included midface degloving (25), endoscopic (23), craniofacial (13), maxillectomy (12), rhinotomy without maxillectomy (5), transoral (5), pterional (2), transcondylar (1), and transcervical (2). Indications for surgery included severe inflammatory disease of the paranasal sinuses with epidural or subdoral abscess, or both (7), cerebrospinal fluid fistula or encephalocele, or both (11), and 40 benign and 30 malignant tumors. Complications occurred in 10 of 88 patients (11%). Real-time intraoperative localization can be applied to cranial base surgery in a variety of scenarios. The instantaneous transfer of imaging data to the surgical field is useful in localizing pathology, enhancing operative safety, and reducing morbidity, thereby improving outcomes. This technology will certainly play an integral role in minimizing complications and improving surgical outcomes as cranial base surgery moves into the next millennium.

Journal Article↗

PubMed2000

Identification of the asexual state of Rhizopus species on histologic tissue sections in a patient with rhinocerebral mucormycosis.

Mucormycosis is an infection caused by a group of fungi in the order Mucorales in the phylum Zygomycota. The most well-known form of this disease is rhinocerebral mucormycosis, which usually develops in diabetic or immunocompromised patients. The fungal hyphal elements are easily detected in biopsy specimens by direct or histologic examination. However, the confirmatory identification of the genus or species requires culture of the specimen. This article presents a case of rhinocerebral mucormycosis in which presumptive identification of the genus was made without microbiologic cultures and was based on the extraordinarily rare appearance of fungal sporangia and sporangiospores in histologic tissue sections. Identification of these structures allowed an early and accurate diagnosis of rhinocerebral invasive mucormycosis.

Adult↗

PubMed2000

Malignant craniopharyngioma.

Craniopharyngiomas are histologically and cytologically benign epithelial tumors of the central nervous system that may be locally aggressive and tend to recur after excision. Malignant change in craniopharyngiomas is extremely rare; we found only 4 such reports in the literature. In this report, we describe a case of squamous cell carcinoma arising in a previously benign craniopharyngioma in a 42-year-old woman. The patient was diagnosed with craniopharyngioma in 1982; during the subsequent 15 years she experienced 7 tumor recurrences, for which surgical resections and 3 courses of radiotherapy were performed. In 1998, the tumor recurred with involvement of the nasal cavity and sphenoid and ethmoid sinuses. Histologic evaluation revealed foci of typical adamantinomatous craniopharyngioma associated with a moderately differentiated squamous cell carcinoma. The transition of typical craniopharyngioma to squamous cell carcinoma was well demonstrated, suggesting that carcinoma arose from the underlying craniopharyngioma. Radiation may have been a contributing factor to carcinogenesis in this case.

Adult↗

PubMed1999

Effect of metal reconstruction plates on cobalt-60 dose distribution: a predictive formula and clinical implications.

PURPOSE: We sought to create a predictive formula for the dose perturbations caused by head and neck reconstruction plates in the delivery of postoperative radiotherapy with 60Co beams. MATERIALS AND METHODS: The dose perturbation effects of Vitallium and Titanium reconstruction plates and flat metal plates of aluminum (13Al), stainless steel (26Fe), tin (50Sn) and lead (82Pb) irradiated with a 60Co beam were measured in polystyrene phantoms using a film dosimetry system. We then used these results to create formulas to predict the effect of a metal reconstruction plate dependent upon its effective atomic number. RESULTS: Percentage dose increases secondary to back scattering were 10% at 1 mm in front of the Vitallium plate and 40% at the plate while the percentage dose decrease was 29% at the plate and 10% 1 mm behind the plate. For the Titanium plate, the percentage dose increase was 5% at 1 mm in front the plate and 25% at the plate while the percentage dose decrease was 20% at the plate and 5% 1 mm behind the plate. For flat plates the percentage dose increases and decreases, respectively, at the plate surfaces were: 13Al (8%, 6%), 26Fe (35%, 16%), 50Sn (60%, 24%), and 82Pb (85%, 13%). A second order polynomial predicting the back scatter and shadowing effects was created, Y = a + bZ + cZ2, where Z is the effective atomic number of the plate while a, b, and c are the following constants: for back scatter a = 0.854 +/- 0.082, b = 0.0212 +/- 0.0044, c = -0.00011 +/- 0.00004 and for shadowing a = 1.108 +/- 0.021, b = -0.0141 +/- 0.0011, c = 0.00014 +/- 0.00001. CONCLUSIONS: It is possible to predict the effect of a metal reconstruction plate upon the delivered postoperative radiotherapy dose. The dose perturbations around the plate only exist for a few millimeters, but this is substantially greater than the thickness of a normal tissue or tumor cell. Perhaps a coating of a low effective atomic number, biologically inert, substance might allow for greater dose homogeneity and decrease the risks of plate failure or tumor recurrence.

Bone Plates↗

PubMed1999

Protein phosphatases 1 and 2A maintain endothelial cells in a resting state, limiting the motility that is needed for the morphogenic process of angiogenesis.

Angiogenesis that is induced by cancers, including those of the head and neck, requires endothelial cells to shift from a nonmotile resting state to an increased level of motility. Using a human microvascular endothelial cell line, this study shows the importance of the serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A) in restricting endothelial cell motility. Treatment of endothelial cells with increasing concentrations of the PP1 and PP2A inhibitor okadaic acid resulted in cell rounding and increased motility, which was accompanied by cytoskeletal disorganization involving a loss of filamentous beta-tubulin and F-actin. These effects occurred at okadaic acid levels that selectively inhibit PP2A and became more prominent with higher levels that inhibit both PP2A and PP1. This study shows the importance of PP1 and PP2A in maintaining cytoskeletal organization, thereby limiting endothelial cell motility, and suggests that pharmacologic approaches to enhance PP1 and PP2A activities may be useful in preventing key events of the angiogenic process.

Cell Division↗

PubMed1998

Mechanism of lymph node metastases: current concepts.

Advances in head and neck surgical techniques with aggressive adjuvant treatment have reduced the incidence of locoregional failure in many types of head and neck cancer. Failure to control distant disease, however, remains of the most frustrating aspects in the care of these patients. A strong foundation in the biology of invasion and metastasis is necessary to understand more clearly the reasons for the development of distant and locally recurrent disease. This article focuses on basic mechanisms of invasion and metastasis in head and neck squamous cell carcinoma.

Head and Neck Neoplasms↗

PubMed1997

Increased recurrence and metastasis in patients whose primary head and neck squamous cell carcinomas secreted granulocyte-macrophage colony-stimulating factor and contained CD34+ natural suppressor cells.

Human head and neck squamous cell carcinomas (HNSCC) that produce high levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) have been shown to contain CD34+ natural suppressor cells that inhibit the activity of intratumoral T-cells. The present study evaluated whether GM-CSF production and the presence of CD34+ cells within primary HNSCC would translate into increased recurrence, metastasis or cancer-related death during the 2 years following surgical excision. Freshly excised primary HNSCC of 20 patients that subsequently developed disease, and of 17 patients that remained with no evidence of disease were analyzed for production of GM-CSF and for CD34+ cell content. The cancers of patients that subsequently developed recurrences or metastatic disease produced almost 4-fold the levels of GM-CSF and had approximately 2.5-fold the number of CD34+ cells as did cancers of patients that remained disease-free. In a second method of analysis, the prognostic significance of high vs. low GM-CSF and CD34+ cell values was evaluated. These analyses showed that patients whose cancers produced high GM-CSF levels or had a high CD34+ cell content had a disproportionately high incidence of recurrence or metastatic disease (94% and 100%, respectively), while the majority of patients whose primary cancers produced low levels of GM-CSF or had a low CD34+ cell content remained disease-free (16% and 19%, respectively). Our results indicate that the presence of CD34+ cells in GM-CSF-producing HNSCC is associated with a poorer prognosis for the cancer patients and suggest the utility of these parameters as prognostic indicators of outcome. Mechanistically, our results suggest that the presence of immune suppressive CD34+ cells in GM-CSF-producing HNSCC leads to increased tumor recurrence or metastasis.

Adult↗

PubMed1997

Heparin-binding growth factor(s) derived from head and neck squamous cell carcinomas induce endothelial cell proliferations.

BACKGROUND: Tumor growth is dependent on the expansion and proliferation of the host vascular system into the primary neoplasm (angiogenesis). The development of an intact vascular system requires migration and proliferation of endothelial cells and assembly into microvessels. Previous studies in our laboratory demonstrated that head and neck squamous cell carcinomas (HNSCC) are angiogenic in vivo. To clarify the mechanism of HNSCC-induced angiogenesis, the present study sought to determine if HNSCCs produced endothelial cell mitogens in vitro. METHODS: Production of PGE-2, TGF-beta, FGF-2 (basic-FGF [fibroblast growth factor]), and vascular endothelial cell growth factor (VEGF) were quantitated by enzyme-linked immunoabsorbant assay (ELISA) in five HNSCC lines. Cell free supernatants of 5 HNSCC lines were tested in a nonradioactive proliferation assay using human umbilical vein endothelial cells (HUVECs). RESULTS: All lines demonstrated enhanced endothelial cell proliferation in a dose-dependent fashion. Fractionation of these supernatants by heparin column chromatography significantly reduced endothelial cell proliferation in the five lines tested (range, 31.7% to 46.23% reduction; mean, 38.14+/-6.02%). Pretreatment with antibody to VEGF but not transforming growth factor (TGF)-beta inhibited endothelial cell proliferation. CONCLUSIONS: These studies indicate HNSCCs produce factor(s) which stimulate endothelial cell proliferation and that VEGF may be involved in HNSCC-induced endothelial cell mitogenesis.

Carcinoma, Squamous Cell↗

PubMed1997

Endothelial cell response to human head and neck squamous cell carcinomas involves downregulation of protein phosphatases-1/2A, cytoskeletal depolymerization and increased motility.

Cancers, such as human head and neck squamous cell carcinomas (HNSCC), have been shown to stimulate angiogenesis by their production of endothelial cell proliferative and motility-stimulatory factors. The present studies to elucidate the intracellular mechanisms that contribute to the motility response of endothelial cells to HNSCC-derived factors showed a decline in the organization of actin filaments and microtubules. This HNSCC-induced decline in cytoskeletal organization coincided with the downregulation of endothelial cell protein phosphatase-1 and 2A (PP-1/2A) activities, and could be mimicked by directly inhibiting these enzyme activities with okadaic acid. These results show that the increased motility of endothelial cells in response to HNSCC-derived angiogenic factors involves downregulation of PP-1/2A activities and, consequently, a decline in cytoskeletal organization.

Actins↗

PubMed1996

Prostaglandin E2-protein kinase A signaling and protein phosphatases-1 and -2A regulate human head and neck squamous cell carcinoma motility, adherence, and cytoskeletal organization.

Human head and neck squamous cell carcinoma (HNSCC) cultures were established from cancers of two patients. These cells were used to study if phosphorylation reactions by protein kinase A (PKA) and dephosphorylation reactions by protein phosphatases-1 and -2A (PP-1/2A) regulate tumor motility and adhesion to extracellular matrix components, and if this might be associated with cytoskeletal reorganization. Both cultures were motile and adherent to collagen I, fibronectin, vitronectin and laminin. Motility and adhesiveness was dependent on production of prostaglandin E2 PGE2 and on PKA activation. Blocking PP-1/2A activity with okadaic acid resulted in a PKA-dependent increase in m otility and, in some instances, adhesiveness by the HNSCC cells. The okadaic acid-induced increase in motility and adhesiveness coincided with a reduction in filamentous actin. These data suggest PKA and PP-1/2A have opposing effects in regulating the motility, adherence, and actin polymerization.

Actins↗

PubMed1996

Macroglossia.

Explore the source record for details and available documents.

Aged↗

PubMed1996

Identifying obstructive sleep apnea in patients presenting for laser-assisted uvulopalatoplasty.

The authors report on a series of 850 patients with snoring who were evaluated for laser-assisted uvulopalatoplasty (LAUP). Stepwise multivariate linear regression was employed to correlate patient symptoms and characteristics to the respiratory disturbance index (RDI). Body mass index, falling asleep while driving, snoring every night, and stopping breathing during sleep were found to correlate strongly with an increasing RDI (variance of 25%). Logistic multivariate linear regression analysis was used to predict the outcome of apnea (RDI>10). This model selected all of the above variables, as well as age, male sex, and the total number of symptoms, as being strong predictors of apnea. A receiver operating characteristic curve was used to describe the ability of this model to predict apnea. The authors conclude that otolaryngologists play an important role in the evaluation of OSAS, especially when a snoring patient may undergo LAUP, and they present an algorithm for the evaluation of such a patient. The authors believe that the clinical assessment, including a thorough history and a complete physical examination, remains extremely important in this evaluation. At present, the authors strongly recommend referral for a PSG if there is any suspicion of OSAS.

Adult↗

PubMed1996

Regulation of the steps of angiogenesis by human head and neck squamous cell carcinomas.

Human head and neck squamous cell carcinoma (HNSCC) cell cultures were established to identify the angiogenic factors they produced and how these factors contribute to two steps of the angiogenic process: endothelial cell proliferation and migration. The HNSCC cells secreted vascular endothelial cell growth factor (VEGF), transforming growth factor-beta (TGF-beta) and prostaglandin E2 (PGE2), but only low levels of basic fibroblast growth factor. Both proliferation-stimulatory and -inhibitory cytokines were produced by the HNSCC cells, with VEGF promoting endothelial cell proliferation, prostaglandins having no effect and TGF-beta downregulating proliferation. Two methods were used to measure endothelial cell migration: migration into a wound in the endothelial cell monolayer and migration across a filter into lower compartments. HNSCC cell supernatants stimulated endothelial cell migration in both migration models. VEGF had no effect on the motility of endothelial cells. However, when TGF-beta activity in the HNSCC supernatants was neutralized with antibody or the production of prostaglandins by HNSCC cells was blocked with indomethacin, the migration-stimulatory activity in the HNSCC cell supernatants was diminished. Adding authentic PGE2 or TGF-beta 1 to endothelial cells mimicked the migration-stimulatory activity of the HNSCC supernatants. Thus, HNSCC-derived VEGF is important in stimulating endothelial cell proliferation, while the antiproliferative effect of TGF-beta and the migration-stimulatory activity of TGF-beta and PGE2 suggest their having a role in the morphogenic processes of angiogenesis.

Carcinoma, Squamous Cell↗