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Biomedical subjects

Brian L Schmidt

Publications and source records attributed to Brian L Schmidt.

At least 19 recordsLinked to original sources
PubMed2006

Peripheral endothelin A receptor antagonism attenuates carcinoma-induced pain.

In this study we investigated the role of endothelin-1 (ET-1) and its peripheral receptor (ET-A) in carcinoma-induced pain in a mouse cancer pain model. Tumors were induced in the hind paw of female mice by local injection of cells derived from a human oral squamous cell carcinoma (SCC). Significant pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, began at four days after SCC inoculation and lasted to 28 days, the last day of measurement. Intra-tumor expression of both ET-1 mRNA and ET-1 protein were significantly upregulated compared to normal tissue, and local administration of the ET-A receptor selective antagonist, BQ-123 (100 microM) significantly elevated withdrawal thresholds, indicating the induction of an antinociceptive effect. These findings support the suggestion that ET-1 and ET-A receptors contribute to the severity of carcinoma-induced soft tissue cancer pain.

Analgesics, Opioid↗
PubMed2006

Elevated salivary endothelin levels in oral cancer patients--a pilot study.

The analysis of saliva has been proposed as a potentially rapid, non-invasive method to monitor and diagnose patients with oral disease. In this study we measured salivary endothelin-1 (ET-1) levels in patients diagnosed with oral squamous cell carcinoma (SCC) prior to treatment. We demonstrate significantly elevated salivary ET-1 levels in the oral SCC group (4.37+/-1.35pg/ml), relative to the control group (1.16+/-0.29pg/ml). ET-1 and ET-1 mRNA were also measured in oral SCC tissue specimens and compared to normal oral epithelial controls. The concentration of ET-1 in the oral SCC specimens was 17.87+/-4.0pg/ml and in the normal epithelial controls the concentration of ET-1 was 5.43+/-2.5pg/ml. ET-1 mRNA was significantly overexpressed in 80% (8/10) of the oral SCC specimens. Our results demonstrate the potential utility of salivary analysis for ET-1 levels to monitor patients at risk for oral SCC.

Adult↗
PubMed2006

Reconstruction of perioral defects following resection for oral squamous cell carcinoma.

PURPOSE: The aim of this study was to review and describe techniques for the reconstruction of large, complex perioral defects after resection of oral squamous cell carcinoma with emphasis on cosmetic and functional outcome. PATIENTS AND METHODS: A review of techniques and selected case presentations using different flap designs for the reconstruction of large perioral defects following resection of squamous cell carcinoma was performed. The Bernard and Karapandzic flaps were used for large lower lip defects. A Zisser flap technique was used to reconstruct a large commissure defect. RESULTS: All reconstructed patients had acceptable functional results and healed without complication. The large lower lip defects were easily closed with the Bernard and Karapandzic flaps. The commissure defect was reconstructed using the Zisser technique. While cosmesis was acceptable in all cases, the commissure was the most difficult region to reconstruct with a favorable appearance. There were no flap failures. The Karapandzic flap led to greater rounding of the commissure area and the composite resection resulted in a lack of lower lip support that was improved with prosthesis. Function was noted to be excellent in the Bernard and Karapandzic flaps, with the patients able to purse lips and blow up balloon-type devices. CONCLUSION: The Bernard, Karapandzic, and Zisser flaps provide a predictable method to reconstruct large perioral defects following resection for oral cancer. Subsequent fabrication of a prosthesis can aid in lip support for the resected area.

Aged, 80 and over↗
PubMed2005

Rare amplicons implicate frequent deregulation of cell fate specification pathways in oral squamous cell carcinoma.

Genomes of solid tumors are characterized by gains and losses of regions, which may contribute to tumorigenesis by altering gene expression. Often the aberrations are extensive, encompassing whole chromosome arms, which makes identification of candidate genes in these regions difficult. Here, we focused on narrow regions of gene amplification to facilitate identification of genetic pathways important in oral squamous cell carcinoma (SCC) development. We used array comparative genomic hybridization (array CGH) to define minimum common amplified regions and then used expression analysis to identify candidate driver genes in amplicons that spanned <3 Mb. We found genes involved in integrin signaling (TLN1), survival (YAP1, BIRC2), and adhesion and migration (TLN1, LAMA3, MMP7), as well as members of the hedgehog (GLI2) and notch (JAG1, RBPSUH, FJX1) pathways to be amplified and overexpressed. Deregulation of these and other members of the hedgehog and notch pathways (HHIP, SMO, DLL1, NOTCH4) implicates deregulation of developmental and differentiation pathways, cell fate misspecification, in oral SCC development.

Carcinoma, Squamous Cell↗
PubMed2005

Tongue and tonsil carcinoma: increasing trends in the U.S. population ages 20-44 years.

BACKGROUND: An increasing incidence of oral carcinoma among young adults has been reported in the U.S. and Europe. Although the association between human papillomavirus infection and tonsillar carcinoma is now well established, to the authors' knowledge little is known about incidence trends in tonsillar carcinoma among younger adults. The objective of the current study was to explore the trends in both oral cavity and pharyngeal squamous cell carcinoma (SCC) in younger U.S. populations, in particular tongue and tonsillar SCC. METHODS: Using the 1973-2001 Surveillance, Epidemiology and End Results (SEER) database, we computed age, race, and site-specific trends of oral and pharyngeal (excluding nasopharynx) carcinoma incidence rates. The percent change (PC) and annual percent change (APC) were computed to explore trends in incidence rates over time. RESULTS: There were 2262 SCC of the oral cavity and 1251 SCC of the pharynx reported to the SEER program from 1973 to 2001 in adults aged 20-44 years. There was a statistically significant increase in the incidence of oral tongue SCC (APC = +2.1; P < 0.001), base of tongue SCC (APC = +1.7; P = 0.04), and palatine tonsil SCC (APC = +3.9; P < 0.001) among younger white individuals, whereas the incidence of SCC in all other oral and pharyngeal sites decreased or remained constant. CONCLUSIONS: The increase in tonsil SCC incidence from 1973 to 2001 paralleled the increase in tongue SCC, whereas SCC in all other oral and pharyngeal sites remained constant or decreased. This may suggest similar etiologic factors for SCC affecting the palatine tonsils and tongue in younger populations.

Adult↗
PubMed2005

Beta-6 Integrin, tenascin-C, and MMP-1 expression in salivary gland neoplasms.

Beta-6 Integrin, tenascin-C, and MMP-1 (matrix metalloproteinase-1) are invasion-related proteins that are frequently overexpressed in many human malignancies. The objective of this study was to determine whether there is overexpression of these molecules in three types of salivary neoplasms showing markedly different behavior. A total of 55 formalin-fixed, paraffin-embedded archived specimens comprising 19 adenoid cystic carcinomas (ACC), 18 polymorphous low-grade adenocarcinomas (PLGA) and 18 pleomorphic adenomas (PA) were utilized in this study. A standard immunohistochemical technique was used to determine the expression levels of beta-6 integrin, tenascin-C, and matrix metalloproteinase-1 (MMP-1) proteins. Sections were assessed semiquantitatively, and tumors were divided into two groups, low-expressors (0-1+) and high-expressors (2-3+) for statistical analysis. Staining was graded as 0 (<1% positive tumor cells), 1+ (<25% positive tumor cells), 2+ (25-50% positive tumor cells), and 3+ (>50% positive cells). The results showed that the malignant tumors were higher expressors of beta-6 than the benign tumors. ACCs showed significantly higher expression of beta-6 than PAs (p=0.04). No significant difference was observed between ACCs and PLGAs. beta-6 expression was rarely seen in normal salivary gland epithelium and was occasionally present in mucosa overlying the tumors. PAs were high-expressors of tenascin-C with a significant difference relative to ACCs (p=0.03). A majority of tumors in all three tumor types showed high expression of MMP1 with expression significantly greater in the PAs compared to ACCs (p=0.008). We conclude that ACCs and PLGAs express beta-6, tenascin-C, and MMP-1, but that their expression patterns are not significantly different. beta-6 appears to be more closely associated with the malignant tumors, and MMP-1 more closely associated with the benign tumors. We believe that beta-6, tenascin-C, and MMP-1 proteins are part of the molecular repertoire used by salivary tumors for malignant invasion and benign tumor expansion.

Adenocarcinoma↗
PubMed2005

Increased nitric oxide levels and iNOS over-expression in oral squamous cell carcinoma.

Inducible nitric oxide synthase (iNOS) is responsible for generating high levels of nitric oxide (NO) in tissues. Increased iNOS expression has been demonstrated in a number of carcinomas including head and neck squamous cell carcinoma (SCC). However, iNOS levels have not been evaluated specifically in oral cavity SCC, or in the precancerous lesions that progress to oral SCC. Also, NO levels have not been measured in oral precancerous or cancerous tissues. We therefore measured iNOS mRNA, iNOS protein and NO in oral SCC, oral dysplasias and normal oral epithelium. We used RT-PCR to quantify and compare iNOS mRNA levels in these oral tissue specimens. We found that iNOS mRNA was overexpressed in 41% of oral SCC but in only 8% of dysplasia specimens (P = 0.003). Immunohistochemistry was used to evaluate iNOS protein levels in oral SCC, oral dysplasias and normal oral epithelium. A significantly higher percentage of oral SCC specimens showed the highest level of iNOS staining relative to the oral dysplasias and normal oral epithelial samples (95% of oral SCC, 50% of dysplasias, and only 0% of normal epithelial controls, P < 0.0001). The positive staining for iNOS was limited to the SCC cells. Production of NO from iNOS was quantified using HPLC and found to be significantly higher in oral SCC (1.45 +/- 0.56 microg/ml) than normal epithelial controls (0.43 +/- 0.26 microg/ml) (P = 0.0013). We conclude that iNOS mRNA levels and NO production are significantly increased, in oral SCC compared to oral dysplasias and normal epithelial controls. These findings suggest that increased iNOS expression and the generation of high NO levels might have a role in oral SCC development.

Carcinoma, Squamous Cell↗
PubMed2004

Overexpression of matrix metalloproteinase-1 and -9 mRNA is associated with progression of oral dysplasia to cancer.

PURPOSE: Although an important risk factor for oral cancer is the presence of epithelial dysplasia, many lesions will not progress to malignancy. Matrix metalloproteinases (MMPs) are zinc-dependent proteinases capable of digesting various structural components of the extracellular matrix. Because MMPs are frequently overexpressed in oral squamous cell carcinoma (SCC), we hypothesized that they are also overexpressed in oral dysplasias; we also hypothesized that those dysplasias that progress to oral cancer express higher levels of MMPs than those lesions that do not progress. EXPERIMENTAL DESIGN: In this retrospective study, we examined changes in MMP-1, -2, and -9 mRNA expression using quantitative TaqMan reverse transcription-polymerase chain reaction in 34 routinely processed oral dysplasias and 15 SCCs obtained from 34 patients. After several years of close follow-up, 19 dysplasias progressed to oral SCC and 15 did not. RESULTS: Overall, MMP-1 mRNA was overexpressed (>2-fold) in 24 of 34 (71%) dysplasias and 13 of 15 (87%) oral SCCs. MMP-2 overexpression was seen in 11 of 34 (32%) dysplasias and 7 of 15 (47%) cancers; for MMP-9, overexpression was identified in 29 of 34 (85%) dysplasias and 15 of 15 (100%) cancers. MMP-1 and -9 levels were significantly higher in the SCCs compared with all oral dysplasias (P = 0.004 and P = 0.01, respectively). MMP-1 and -9 mRNA levels were significantly higher in the oral dysplasias that progressed to oral cancer compared with those that did not (P = 0.04 and P = 0.002, respectively). CONCLUSIONS: Levels of MMP-1 and -9 mRNA may be markers of malignant transformation of oral dysplasia to oral cancer.

Carcinoma, Squamous Cell↗
PubMed2004

Tobacco smoking history and presentation of oral squamous cell carcinoma.

PURPOSE: The association between tobacco smoking and oral squamous cell carcinoma is well established. However, few studies have evaluated the smoking history based on a smoking versus never-smoking history or analyzed the relationship between smoking history and site and stage of presentation. The purpose of this study was to examine the relationship between smoking versus never-smoking history and the stage and site of presentation of oral squamous cell carcinoma. PATIENTS AND METHODS: The design of this study was a retrospective review of all patients presented at the Legacy Emanuel Hospital Head and Neck Tumor Board in Portland, Oregon, with a biopsy-proven oral squamous cell carcinoma between 1998 and 2000. Data collected included age, gender, smoking history (smoker versus never smoker), pack-years of tobacco, site, and stage (T, N, and group stage) at presentation. RESULTS: A total of 67 patients were reviewed; 33% of patients were never smokers and 67% of patients had a history of smoking with an average of 49.4 pack-years. The floor of mouth and gingiva were the most commonly affected sites. There was a statistically significant difference between site of presentation and a history of smoking (P =.0007). The 2 sites that showed a significant association with smoking were posterolateral tongue and floor of mouth. CONCLUSIONS: The findings of this study demonstrate that approximately one third of patients with oral squamous cell carcinoma will report that they have never smoked. There was a strong association between a history of smoking and carcinoma involving the posterolateral tongue and floor of mouth.

Adult↗
PubMed2004

Neurosensory changes after liquid nitrogen cryotherapy.

PURPOSE: The study goal was to evaluate neurosensory changes after liquid nitrogen cryotherapy in the management of mandibular lesions in close proximity to the inferior alveolar nerve. PATIENTS AND METHODS: The design of the study was a retrospective review. Sixteen patients with posterior mandibular lesions (15 odontogenic keratocysts and 1 fibromyxoma) in close proximity to the inferior alveolar nerve were treated with a standardized enucleation and cryotherapy technique. Postoperative evaluation included patients report of symptoms and formal neurosensory testing. RESULTS: All patients had altered sensation in the distribution of the inferior alveolar nerve immediately after cryotherapy. Two patients experienced anesthesia, and the remaining 14 patients showed paresthesia. The average time for return or improvement in sensation was 91 days (range, 6 to 235 days). The average time of follow-up was 2.6 years (range, 0.5 to 7.3 years). At the time of last follow-up, no patients had anesthesia or dysesthesia. Four patients had full return of sensation and 12 patients had paresthesia. No patients reported significant difficulty from abnormal nerve function. All 16 patients experienced some return of sensation; 9 patients had full or near full return of sensation. CONCLUSIONS: Based on these results, the combination of enucleation and liquid nitrogen cryotherapy produces minimal alteration of inferior alveolar nerve function.

Adolescent↗
PubMed2004

Reconstruction of extensive maxillary defects using zygomaticus implants.

PURPOSE: Maxillary reconstruction after maxillectomy remains a great challenge for the reconstructive oral and maxillofacial surgeon. This article is a clinical retrospective analysis of patients reconstructed with zygomaticus implants after maxillary ablation. PATIENTS AND METHODS: The design of the study was a retrospective review of 9 patients requiring near-total or total maxillectomy for pathologic reasons. Clinical records, photographs, and radiographs were studied. Financial billing statements were reviewed to determine charges for implant reconstruction and method of payment. RESULTS: Maxillary reconstruction using zygomaticus and standard endosseous implants was performed in 9 patients. Maxillary resection was performed for the following reasons: salivary gland malignancy (n = 2), squamous cell carcinoma (n = 5), maxillary mucormycosis (n = 1), and extensive maxillary atrophy and infection secondary to subperiosteal maxillary implant placement (n = 1). A total of 28 zygomaticus implants and 10 standard endosseous implants were used to reconstruct the 9 patients. Six zygomaticus implants and 3 standard endosseous implants failed. The time of zygomaticus implant placement ranged from placement at the time of resection to 3.2 years after the resection. Five patients received radiation therapy. Five patients have been reconstructed with a maxillary obturator and have been functioning with the prosthesis for a minimum of 2 years. CONCLUSION: The combination of zygomaticus and standard endosseous implants can be used to reliably reconstruct patients after extensive resection of the maxilla.

Aged↗
PubMed2004

Evaluation of pain in patients with oral squamous cell carcinoma.

UNLABELLED: In this study we have developed and tested a novel pain questionnaire to measure the pain experienced by patients with oral squamous cell carcinoma. The questionnaire consisted of 8 questions rated by the patient on a visual analog scale. Patients completed the questionnaire at the time of initial presentation before surgical treatment. None of the patients were taking analgesics. The responses were then scored and compiled with patient data and pathology reports. Of the 15 completed questionnaires, 14 patients reported some level of functional restriction from pain (mean, 46.6 +/- 25.2, scale of 0 to 100 mm). On average, patients experienced significantly higher function-related, rather than spontaneous, pain intensity and sharpness. Men (n = 8) had a significantly higher level of function-related pain intensity and sharpness than women had (n = 7). There was a strong correlation between nodal disease and increased levels of spontaneous intensity, sharpness, throbbing, and overall functional restriction. PERSPECTIVE: The results of this study indicate the heterogeneous nature and function dependence of oral cancer pain. The questionnaire we have developed in this study will allow for correlations between pain parameters and specific tumor biology in future studies.

Aged↗
PubMed2003

Alphavbeta6-Fyn signaling promotes oral cancer progression.

We have previously shown that the integrin beta6 is neo-expressed in invasive oral squamous cell carcinoma (SCC) and is correlated with oral tumor progression. However, the mechanism by which the integrin beta6 promotes oral tumor progression is not well understood. The purpose of the present study was to determine whether integrin beta6 signaling activates Fyn and thus promotes oral squamous cell carcinoma progression. We analyzed the integrin beta6 signaling complex and investigated the function of these signaling molecules in oral SCC cells. We found that, upon ligation of the integrin beta6 with fibronectin, beta6 complexed with Fyn and activated it. The activation of Fyn recruited and activated focal adhesion kinase to this complex. This complex was necessary to activate Shc and to couple beta6 signaling to the Raf-ERK/MAPK pathway. This pathway transcriptionally activated the matrix metalloproteinase-3 gene and promoted oral SCC cell proliferation and experimental metastasis in vivo. These findings indicate that integrin beta6 signaling activates Fyn and thus promotes oral cancer progression.

Animals↗
PubMed2003

Response of neuropathic trigeminal pain to the combination of low-dose nalbuphine plus naloxone in humans.

We report on the response of medically refractory neuropathic trigeminal pain in three patients to intravenous administration of a combination of the kappa-partial agonist opioid nalbuphine and the opioid antagonist naloxone. Each of the three patients had developed a painful peripheral neuropathy as a complication of chemical or mechanical injury to the trigeminal nerve. Each patient had been tried on a number of analgesics, including mu-opioids, and had not gained relief or was not able to tolerate side effects of the medications. Pain intensity was measured for 3 h following drug administration using a 10 cm visual analog scale. All three patients reported marked decrease in pain following administration of the nalbuphine and naloxone combination. These findings suggest a novel approach to the management for neuropathic pain.

Adult↗