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Biomedical subjects

Robert L Ferris

Publications and source records attributed to Robert L Ferris.

At least 37 records · Page 2Linked to original sources
PubMed2005

Multiplexed analysis of serum cytokines as biomarkers in squamous cell carcinoma of the head and neck patients.

OBJECTIVE: Our objective was to characterize cytokine profiles in the systemic circulation of patients with active squamous cell carcinoma of the head and neck (SCCHN) compared with long-term tobacco smokers as controls. Furthermore, we hypothesized that persistent immune dysregulation in patients cured of their disease may be reflected in altered cytokine profiles in the systemic circulation. STUDY DESIGN: Retrospective, case-control study. METHODS: Using three well-defined clinical cohorts of SCCHN patients and smoker controls, we analyzed 100 microL of serum for a panel of 10 cytokines to determine whether serum cytokine profiles could distinguish clinically defined groups of SCCHN patients. Statistical analysis of multiplexed cytokine profiles was applied to classify three clinically defined groups: active SCCHN patients, treated SCCHN patients with no evidence of disease for over 3 years, and matched disease-free controls. Discrimination of outcome status was accomplished using classification trees, and 10-fold cross-validation was implemented to assess classification accuracy using independent data. RESULTS: We show that multiplexed cytokine and chemokine profiling may be performed to reflect the immune status of SCCHN patients. Selected cytokine profiles indicate that immunologic responses to carcinogenesis may not normalize even in the absence of tumor for over 3 years. CONCLUSION: Multiplexed serum cytokine profiles may be applicable to early detection, for screening those at high risk for SCCHN, and as clinically predictive biomarkers of disease status in successfully treated patients.

Biomarkers↗
PubMed2005

Diagnostic utility of positron emission tomography-computed tomography for predicting malignancy in cystic neck masses in adults.

OBJECTIVES: Combined positron emission tomography and computed tomography (PET-CT) is used for the diagnostic evaluation and staging of squamous cell carcinoma of the head and neck (SCCHN). By superimposing anatomic localization of CT with the physiologic data of PET, occult primary and metastatic neoplasms might be identified. Because the diagnostic algorithm for cystic neck masses in adults often overlaps with the work-up of cancer of unknown primary site, we evaluated the utility of PET-CT scans to identify the presence of malignancy and the location of primary tumor. STUDY DESIGN: Single-institution retrospective case review series. METHODS: We reviewed the PET-CT imaging of cystic neck masses occurring in five patients over 40 years of age with significant risk factors for SCCHN and correlated this information with histopathology. RESULTS: In each patient in our series, the PET portion of a combined PET-CT was misleading, whereas the CT examination was more suggestive of the correct pathology. Ultimately, clinical judgment and endoscopic evaluation, guided by CT findings, were most valuable for distinguishing malignant versus benign processes and identifying the primary tumor sites. CONCLUSIONS: PET-CT may not be a reliable modality for identifying malignancy in adults with suspicious cystic neck masses. A thorough clinical evaluation by an experienced head and neck surgeon, in conjunction with contrast-enhanced CT, may be sufficient to facilitate the optimal management of such patients.

Adult↗
PubMed2005

Chemokine receptors 6 and 7 identify a metastatic expression pattern in squamous cell carcinoma of the head and neck.

Squamous cell carcinoma of the head and neck (HNSCC) metastasizes predictably to locoregional, cervical lymph nodes. Tumor cells can express various receptors that facilitate metastatic spread to lymph nodes and other nonlymphoid organs. Chemokine receptors (CCRs), normally expressed on lymphocytes, control immune and inflammatory cell migration, providing a link between innate and adaptive immunity. CCR expression was evaluated in HNSCC, and we showed a consistent pattern of CCR6 downregulation and upregulation of CCR7 in metastatic cells and tissues. Functional assays indicate that these surface receptors were functional on metastatic tumor cells. CCR6 downregulation is consistent with its decreased expression in cells emigrating from peripheral mucosal sites, while CCR7, important for homing of immune cells to secondary lymphoid organs, was significantly upregulated. Thus, CCR6, CCR7 and their ligands, normally important in controlling immune cell trafficking in response to inflammatory stimuli, may have an important role in determining the metastasis of HNSCC cells in vivo. Our data indicate that inhibition of CCR signaling may provide a targeted molecular therapy to prevent HNSCC metastasis.

Biomarkers, Tumor↗
PubMed2005

Human leukocyte antigen (HLA) class I defects in head and neck cancer: molecular mechanisms and clinical significance.

The potential role of immunological events in the pathogenesis and clinical course of head and neck squamous cell carcinoma (SCCHN) has stimulated interest in the characterization of HLA class I antigen expression in SCCHN lesions, because these molecules play an important role in the interaction of malignant cells with the host's immune system. Therefore in this paper, following a description of the methodology used to analyze HLA class I antigen expression in normal tissues and in malignant lesions, we have reviewed data about the frequency of HLA class I antigen defects in about 500 primary and in about 25 metastatic SCCHN lesions. The mean frequency of total HLA class I antigen loss in primary and metastatic lesions is approx 15% and 40%, respectively. The mean frequency of selective HLA class I antigen loss in primary lesions is approx 37%. This type of abnormality has not been investigated in metastatic lesions so far. The molecular mechanisms underlying HLA class I antigen defects in SCCHN cells have been investigated to a limited extent. The available information suggests that structural defects in beta2m genes are rare. In contrast, functional abnormalities of the antigen processing machinery (APM) components are frequent in SCCHN cells. The latter abnormalities are likely to account for the unusual finding that most of SCCHN cell lines are resistant in vitro to HLA class I antigen restricted, tumor antigen (TA)-specific CTL recognition under basal conditions in spite of the expression of TA and HLA class I antigens. CTL recognition of SCCHN cells is restored by incubation with IFN-gamma. These in vitro findings provide a mechanism for the association between APM component defects in SCCHN lesions and clinical course of the disease and imply that T cell-based immunotherapy of SCCHN may benefit from the intralesional administration of IFN-gamma.

Animals↗
PubMed2004

Correlation of protease-activated receptor-1 with differentiation markers in squamous cell carcinoma of the head and neck and its implication in lymph node metastasis.

PURPOSE: Protease-activated receptor-1 (PAR-1) is a G-protein-coupled receptor that contributes to multiple signal transduction pathways. Although the functions of PAR-1 in many normal cells, such as platelets and astrocytes, have been well studied, its roles in cancer progression and metastasis have not been fully elucidated, and studies to date appear contradictory. EXPERIMENTAL DESIGN: To clarify the function of PAR-1 in metastasis of squamous cell carcinoma of the head and neck (SCCHN), we examined PAR-1 expression in clinical specimens by immunohistochemistry and in SCCHN cell lines by immunoblotting. Furthermore, par-1 cDNA-transfected SCCHN cell lines were also used to verify PAR-1-mediated pathway. RESULTS: The metastatic tumors showed a lower percentage of PAR-1-positive cells (46%) and lower levels of PAR-1 expression (median weight index = 10) than node negative primary tumors (80% and median weight index = 60, respectively). In addition, expression level of PAR-1 positively correlated with levels of keratinocyte differentiation markers keratin-1, -10, and -11. Additional studies using sense and antisense par-1 cDNA-transfected SCCHN cell lines illustrated that the presence of PAR-1 was required for the expression of involucrin, a keratinocyte differentiation marker. PAR-1 expression also contributes to activation of the mitogen-activated protein kinase (MAPK) pathway. Blocking MAPK activation by a mitogen-activated protein/extracellular signal-regulated kinase inhibitor, not by a phosphatidylinositol 3'-kinase inhibitor, reduced level of involucrin, suggesting that regulation of involucrin by PAR-1 is partially through the MAPK signaling pathway. CONCLUSIONS: Our study suggests that PAR-1 signaling induces differentiation markers in SCCHN cells, and its expression is conversely correlated with cervical lymph node metastasis.

Adult↗
PubMed2004

Characterization of the human nicotinic acetylcholine receptor subunit alpha (alpha) 9 (CHRNA9) and alpha (alpha) 10 (CHRNA10) in lymphocytes.

Though the nicotinic acetylcholine receptor (nAChR) subunits alpha9 and alpha 10 have been thoroughly characterized within hair cells of the organ of Corti in the inner ear, prior studies have shown that they are also expressed in lymphocytes. In this report, we sought to more definitively characterize the nAChR subunits alpha9 and alpha10 within various populations of human lymphocytes. Using a combination of techniques, including RT-PCR, single-cell RT-PCR, Northern and western blot analysis, and immunofluorescence, expression of both alpha9 and alpha 10 was demonstrated in purified populations of T-cells (CD3+, CD4+, CD8+ and the Jurkat, MT2 and CEM T-cell lines) and B-cells (CD19+, CD80+ and EBV-immortalized B-cells). Single-lymphocyte recording techniques failed to identify an ionic current in response to applied acetylcholine in either T-cells or B-cells. These results clearly demonstrate the presence of these nicotinic receptor subunits within several populations of human lymphocytes, implicating their role in the immune response. However, a lack of demonstrated response to applied acetylcholine using standard single-cell recording techniques suggests a physiology different than that seen in hair cells of the inner ear.

Acetylcholine↗
PubMed2004

Effect of human papillomavirus-16 infection on CD8+ T-cell recognition of a wild-type sequence p53264-272 peptide in patients with squamous cell carcinoma of the head and neck.

PURPOSE: Wild-type sequence (wt) p53 peptides are attractive candidates for broadly applicable cancer vaccines, currently considered primarily for patients whose tumors overexpress p53. Circumstances exist, however, where increased p53 degradation may result in appreciable presentation of p53-derived peptides, despite low p53 expression. Squamous cell carcinoma of the head and neck is associated with oncogenic human papillomavirus (HPV) subtypes, which inactivate p53 through proteasomal degradation. The criterion of p53 overexpression would exclude these individuals from wt p53-based immunotherapy. EXPERIMENTAL DESIGN: We tested the correlation of HPV infection with enhanced antigenicity of the p53 protein and postulated that removal of HPV-16(+) tumors with enhanced p53(264)-(272) peptide presentation might lead to a drop in T cells specific for this peptide in vivo. Circulating frequencies of T cells specific for the HLA A*0201:p53(264)-(272) complex were measured ex vivo using dimeric HLA:peptide complexes in 15 head and neck cancer patients before and 6 months after tumor excision. RESULTS: CD8+ T-cell recognition of HLA A*0201 restricted wt p53(264)-(272) peptide presented by HPV-16(-) squamous cell carcinoma of the head and neck lines was enhanced by HPV-16 E6 expression, sometimes exceeding that of a naturally transformed, HPV-16(+) wt p53 expressing squamous cell carcinoma of the head and neck cell line. In patients with HPV-16(-) tumors, the frequency of wt p53(264-272)-specific T cells remained largely unchanged after tumor removal. However, a significant decline in frequency of anti-p53(264-272) T cells was observed postoperatively in HPV-16(+) patients (P < 0.005). CONCLUSIONS: Recognition of HPV-associated squamous cell carcinoma of the head and neck appears associated with levels of wt p53-specific T cells and inversely with p53 expression. p53 peptides may be useful tumor antigens for squamous cell carcinoma of the head and neck immunotherapy in addition to viral gene products.

Aged↗
PubMed2004

Decreased absolute counts of T lymphocyte subsets and their relation to disease in squamous cell carcinoma of the head and neck.

PURPOSE: Apoptosis of circulating CD8+ T cells seen in patients with squamous cell carcinoma of the head and neck [SCCHN (Hoffmann T, et al. Clin Cancer Res 2002;8:2553-62)] suggested a possibility of lymphocyte imbalance. Therefore, absolute numbers and percentages of lymphocyte subsets were examined in the peripheral blood of SCCHN patients and controls. EXPERIMENTAL DESIGN: Venous blood was obtained from 146 patients with SCCHN and 54 normal volunteers. Absolute numbers of CD3+, CD4+, and CD8+ T lymphocytes were determined using fluorobeads in a flow cytometry-based technique. Percentages of T lymphocyte subsets were also evaluated by flow cytometry. The patients were grouped at the time of blood draw [active versus no evidence of disease (NED), type of therapy administered, and the length of follow-up]. RESULTS: Patients with SCCHN had significantly lower absolute numbers of CD3+ CD4+, and CD8+ T cells than normal controls. However, no differences in the percentages of T-cell subsets between patients and normal controls were observed. Patients with active disease had significantly lower CD3+ and CD4+ T-cell counts than those with NED. Patients who had NED after surgery and radiotherapy had the lowest T-cell counts among the NED cohort. Patients who had NED for >2 years did not recover their T-cell counts, and the T-cell imbalance was evident many years after curative surgery. The tumor-node-metastasis (TNM) stage or site of the disease was not related to the absolute T-cell count. Patients with recurrent disease at the time of blood draw tended to have the lowest CD4+ T-cell counts. CONCLUSIONS: Patients with SCCHN have altered lymphocyte homeostasis, which persists for months or years after curative therapies.

Adult↗
PubMed2004

Expression pattern of chemokine receptor 6 (CCR6) and CCR7 in squamous cell carcinoma of the head and neck identifies a novel metastatic phenotype.

Squamous cell carcinoma of the head and neck (SCCHN) metastasizes predictably to cervical lymph nodes, with low rates of distant metastases. Tumor cells can express various receptors that facilitate such metastatic spread to lymph nodes and other nonlymphoid organs. Chemokine receptors (CCR), normally expressed on lymphocytes, control immune and inflammatory cell migration, providing a link between innate and adaptive immunity. Chemokine receptor expression was evaluated in SCCHN, using paired primary and metastatic tumors cell lines, and paired primary and metastatic biopsies from the same patients. Quantitative reverse transcription-PCR showed a consistent pattern of CCR6 down-regulation and up-regulation of CCR7 in metastatic cells and tissues. Chemotaxis assays, ligand-induced receptor down-regulation, and specific antibody blocking experiments supported the quantitative reverse transcription-PCR results, indicating that these surface receptors were functional on metastatic tumor cells. Cells derived from a highly metastatic mouse model of SCCHN were used to confirm CCR7 up-regulation in tumor cells with higher metastatic potential. CCR6 down-regulation is consistent with its decreased expression in cells emigrating from peripheral mucosal sites, whereas CCR7, important for homing of immune cells to secondary lymphoid organs, was significantly up-regulated. Thus, CCR6, CCR7, and their ligands, normally important in controlling immune cell trafficking in response to inflammatory stimuli, may have an important role in determining the metastasis of SCCHN cells in vivo.

Carcinoma, Squamous Cell↗
PubMed2004

Molecular biology of primary hyperparathyroidism.

As molecular biology and genetic mapping receive wider application to human disease, genetic alterations have been identified with increased frequency in some patients with primary hyperparathyroidism(HPT). These alterations have been found in molecules related to cellular signaling and growth (RET proto-oncogene)and in tumor suppressors that control cell cycle progression and gene transcription (cyclin D1 and the MEN1 gene product. Although primary HPT can usually be treated surgically without knowledge of which specific genetic alteration has occurred, this information may assist clinicians in identifying which patients will go on to develop multiglandular or recurrent disease. In addition,such an approach would facilitate more appropriate postoperative surveillance, as well as counseling and screening of family members who may be at high risk for HPT.

Adenoma↗
PubMed2004

Elective neck dissection and survival in patients with squamous cell carcinoma of the oral cavity and oropharynx.

OBJECTIVE/HYPOTHESIS: The utility of elective neck dissection in the management of patients with oral cavity and oropharyngeal cancer who present without neck metastases remains controversial. The study addressed the question of whether elective neck dissection improves regional control and survival in patients with squamous cell carcinoma of the oral cavity and oropharynx presenting with T1/T2 node-negative disease. STUDY DESIGN: A nonrandomized, uncontrolled retrospective chart review. METHODS: A nonrandomized, uncontrolled retrospective chart review was performed. Resection of the primary tumor was performed in all patients. The neck was observed in one group, and elective neck dissection was performed for patients in another group. RESULTS: The study data indicated that elective neck dissection significantly improves regional control and regional recurrence-free survival. Elective neck dissection when compared with observation of the neck did not improve overall survival. CONCLUSION: Elective neck dissection reduces regional recurrence and may extend disease-free survival.

Adult↗
PubMed2004

Progress in head and neck cancer immunotherapy: can tolerance and immune suppression be reversed?

The incidence of squamous cell carcinoma of the head and neck (SCCHN) is greater than 40,000 cases per year in the United States, and approximately 500,000 cases annually worldwide. Despite significant advances in detection, ablation, and reconstruction, survival has not improved appreciably over the past few decades. Therefore, novel approaches are necessary to provide head and neck oncologists with a more effective armamentarium against this challenging disease. Cancer immunotherapy describes various approaches to expand and activate the immune system to control tumor growth in vivo. So far, immunotherapy appears to have had applicability in conjunction with other therapeutic interventions that treat residual tumor cells after therapy or to reduce the occurrence of second primary tumors. In particular, diseases such as SCCHN are attractive candidates for novel therapeutic approaches, since the standard treatments have not yet successfully controlled this disease with sufficiently high success rates. This article reviews adjuvant immunotherapeutic strategies currently in trials or under development for SCCHN patients, including vaccination or cytokine immunostimulation.

Adjuvants, Immunologic↗
PubMed2003

Early hemodynamic changes after renal transplantation: determinants of low central venous pressure in the recipients and correlation with acute renal dysfunction.

BACKGROUND: Transplantation of organs leads to several physiologic changes in the recipients who, during their anephric state on chronic hemodialysis, have increased total body water and several electrolyte imbalances. Several abnormal parameters are observed in the physiology of the renal recipient. The central venous pressure (CVP) in the recipient invariably declines despite vigorous fluid resuscitation for reasons that are not clear at the present time. MATERIAL/METHODS: We studied 77 kidney transplants retrospectively, in which we observed a significant decline in central venous pressure (CVP) in the immediate posttransplant period. This phenomenon occurred despite aggressive fluid management and positive fluid balances averaging nearly four liters. Our analysis included the time course of the phenomenon itself as well as a detailed comparison of various parameters in the recipient and the renal graft for possible correlation with this consistent decline in CVP. RESULTS: Neither the absolute CVP nor the drop in CVP appeared to influence the rate of ATN. Interestingly, we found that the kinetics of the decline in CVP were remarkably similar in recipients of both cadaveric and living-related kidneys. CONCLUSIONS: This finding suggests that the reperfusion injury or a related effect may be responsible for the clinical phenomenon presented in this study.

Adult↗
PubMed2002

Diagnostic assessment of laryngeal cancer.

Laryngeal carcinoma must be diagnosed expeditiously to maximize curative efforts. Our approach combines useful aspects of the patient's presentation with application of appropriate diagnostic modalities. Newer methods of assessment and follow-up are being scientifically validated and will likely enhance the diagnostic efforts of the head and neck surgical oncologist.

Alcohol Drinking↗
PubMed2002

Alterations in the frequency of dendritic cell subsets in the peripheral circulation of patients with squamous cell carcinomas of the head and neck.

Patients with advanced squamous cell carcinomas of the head and neck (SCCHN) are frequently immunocompromised. Dendritic cells (DCs) are potent antigen-presenting cells that play a role in antitumor immune responses. Using multicolor flow cytometry, the percentages of lineage-negative (LIN(-)) and DR(+) DC precursors, as well as their LIN(-)DR(+)CD11c(+) (myeloid) and LIN(-)DR(+)CD123(+) (lymphoid) subsets, were determined in the peripheral blood of 36 patients with SCCHN before surgery. Peripheral blood mononuclear cells of 28 age- and sex-matched healthy individuals were used as controls. The proportions of LIN(-)DR(+) cells were found to be comparable in the circulation of patients and controls. However, the relative level of DR expression in LIN(-)DR(+) DC was lower in patients than in controls, suggesting a difference in the maturity of DC. The relative proportion of LIN(-)DR(+)CD123(+) cells in the LIN(-)DR(+) subset of DC did not differ significantly in patients compared with normal individuals. However, the percentage of myeloid-derived LIN(-)DR(+)CD11c(+) DCs was significantly lower (P < 0.002) in SCCHN patients than in controls. Of the 13 patients who were restudied 6 weeks after surgery, 9 showed an increase of the myeloid-derived LIN(-)DR(+)CD11c(+) DC subset postoperatively. This observation suggests that deficiency in the myeloid-derived DC precursors in patients with SCCHN is related to the presence of tumor and is reversible. An overall decrease in the myeloid-derived subset of DC could contribute to the failure of SCCHN patients to develop effective antitumor immune responses.

Adult↗