Biomedical subjects

A A Chalian

Publications and source records attributed to A A Chalian.

36 records · Page 2Linked to original sources

PubMed1998

Molecular and immunological analysis of genetic prostate specific antigen (PSA) vaccine.

Nucleic acid immunization has been investigated as immunotherapy for infectious diseases as well as for treating specific types of cancers. In this approach, nucleic acid expression cassettes are directly inoculated into the host, whose transfected cells become the production source of novel and possibly immunologically foreign protein. We have developed a DNA vaccine construct which encodes for PSA by cloning a cDNA for PSA into a mammalian expression vector under control of a CMV promoter. We investigated and characterized the immunogenicity of PSA DNA expression cassettes in mice. PSA-specific immune responses induced in vivo by immunization were characterized by enzyme-linked immunosorbent assay (ELISA), T helper proliferation cytotoxic T lymphocyte (CTL), and flow cytometry assays. We observed a strong and persistent antibody response against PSA for at least 180 days following immunization. In addition, a significant T helper cell proliferation was observed against PSA protein. Using synthetic peptides spanning the PSA open frame, we identified four dominant T helper epitopes of PSA. Furthermore, immunization with PSA plasmid induced MHC Class I CD8+ T cell-restricted cytotoxic T lymphocyte response against tumor cell targets expressing PSA. The prostate represents a very specific functional organ critical for reproduction but not for the health and survival of the individual. Understanding the immunogenicity of PSA DNA immunization cassettes offers insight into the possible use of this tumor-associated antigen as a target for immunotherapy. These results demonstrate the ability of the genetic PSA to serve as a specific immune target capable of generating both humoral and cellular immune responses in vivo.

Animals↗

PubMed1998

CD8 positive T cells influence antigen-specific immune responses through the expression of chemokines.

The potential roles of CD8(+) T-cell-induced chemokines in the expansion of immune responses were examined using DNA immunogen constructs as model antigens. We coimmunized cDNA expression cassettes encoding the alpha-chemokines IL-8 and SDF-1alpha and the beta-chemokines MIP-1alpha, RANTES, and MCP-1 along with DNA immunogens and analyzed the resulting antigen-specific immune responses. In a manner more similar to the traditional immune modulatory role of CD4(+) T cells via the expression of Th1 or Th2 cytokines, CD8(+) T cells appeared to play an important role in immune expansion and effector function by producing chemokines. For instance, IL-8 was a strong inducer of CD4(+) T cells, indicated by strong T helper proliferative responses as well as an enhancement of antibody responses. MIP-1alpha had a dramatic effect on antibody responses and modulated the shift of immune responses to a Th2-type response. RANTES coimmunization enhanced the levels of antigen-specific Th1 and cytotoxic T lymphocyte (CTL) responses. Among the chemokines examined, MCP-1 was the most potent activator of CD8(+) CTL activity. The enhanced CTL results are supported by the increased expression of Th1 cytokines IFN-gamma and TNF-alpha and the reduction of IgG1/IgG2a ratio. Our results support that CD8(+) T cells may expand both humoral and cellular responses in vivo through the elaboration of specific chemokines at the peripheral site of infection during the effector stage of the immune response.

AIDS Vaccines↗

PubMed1998

Image-guided fine-needle aspiration of the head and neck: five years' experience.

OBJECTIVE: To evaluate the diagnostic utility of image-guided fine-needle aspiration (FNA) in the head and neck. DESIGN: All image-guided FNAs of the head and neck performed January 1992 through June 1997 were included. All cytohistopathologic data were reviewed and collated. A slide review was performed in all cases with cytohistologic discrepancies. SETTING: The Department of Radiology, University of Pennsylvania Medical Center, Philadelphia. PATIENTS: Patients with deep-seated or poorly localized masses in the head and neck, representing both primary or recurrent/metastatic lesions, were referred. RESULTS: There were 111 computed tomography-guided FNAs performed in 109 patients. Sites sampled included parapharyngeal (n = 20), parotid or submandibular (n= 25), thyroid (34), and neck, paratracheal/paraesophageal, skull base, and paraspinal (n = 32). Diagnostic samples were obtained in 93 cases (83.8%). The procedures were well tolerated, without long-term complications. Cytologic examination detected a total of 39 malignancies, 24 of which were confirmed histologically. Eleven of the remaining malignant FNA cases reflected recurrent tumor; there were 3 false-positive FNA cases (2.7%), 2 in the setting of previous surgery and/or radiation therapy. There were 2 false-negative aspirates from sites deep in the neck (1.8%) among 7 of the 35 patients with benign aspirates who underwent surgery. Twenty six patients underwent ultrasound-guided FNA (thyroid gland only), revealing 1 papillary carcinoma and 1 intrathyroidal parathyroid gland, both of which were confirmed histologically. The findings in the aspirates from the rest of the patients were benign (n = 18), Hurthle cell neoplasm (n = 1), and nondiagnostic (n = 5). CONCLUSIONS: (1) The cytologic findings were supported clinically and/or histologically in 86 (92%) of the 93 diagnostic computed tomography-guided FNA cases. (2) Unnecessary surgery was avoided in 37% of the patients with recurrent tumor or benign diagnoses by cytologic assessment. (3) Potential pitfalls include false-positive diagnoses after radiation therapy and procedural or sampling limitations for deep neck and paraspinal lesions.

Adolescent↗

PubMed1998

Prophylactic gastrostomy tubes in patients undergoing intensive irradiation for cancer of the head and neck.

BACKGROUND: Most patients receiving accelerated fractionation radiotherapy or chemoradiotherapy for head and neck cancer experience severe mucositis. This can lead to decreased oral intake, resulting in dehydration, severe malnutrition, hospitalization, and/or interruption of radiotherapy. OBJECTIVE: To evaluate the effect of prophylactic gastrostomy tubes (PGTs) on the rates of weight loss, unplanned interruptions, and hospitalization during high-intensity head and neck radiotherapy. METHODS: A retrospective review was performed on 88 patients treated for locally advanced head and neck cancer with accelerated twice-a-day radiation (n = 59) or concurrent chemoradiotherapy (n = 29). Prophylactic gastrostomy tubes were placed in 36 (41%) of patients in anticipation of increased acute toxic effects from treatment. The remaining patients without PGTs served as a control group. RESULTS: Patients without PGTs lost an average 3.1 kg compared with 7.0 kg in the control group (P<.001). There were significantly fewer hospitalizations for nutritional or dehydration issues in those with PGTs than in the control group (13% vs 34%; P = .04, chi2 test). Among those with good performance status, no patient with a PGT required a treatment interruption, compared with 18% of patients without a PGT (P = .08). Sixteen patients (31%) in the control group underwent therapeutic gastrostomy tube placement during or after radiation therapy. CONCLUSIONS: The use of PGTs significantly reduces weight loss and the rate of hospitalization for dehydration and complications of mucositis. Treatment interruptions may also be avoided by the use of PGTs in patients with good performance status. We encourage patients scheduled for intensive radiation therapy to receive a PGT.

Carcinoma, Squamous Cell↗

PubMed1998

Modulation of amplitude and direction of in vivo immune responses by co-administration of cytokine gene expression cassettes with DNA immunogens.

Immunization with nucleic acids has been shown to induce both antigen-specific cellular and humoral immune responses in vivo. We hypothesize that immunization with DNA could be enhanced by directing specific immune responses induced by the vaccine based on the differential correlates of protection known for a particular pathogen. Recently we and others reported that specific immune responses generated by DNA vaccine could be modulated by co-delivery of gene expression cassettes encoding for IL-12, granulocyte-macrophage colony-stimulating factor and the co-stimulatory molecule CD86. To further engineer the immune response in vivo, we investigated the induction and regulation of immune responses following the co-delivery of pro-inflammatory cytokine (IL-1 alpha, TNF-alpha, and TNF-beta), Th1 cytokine (IL-2, IL-12, IL-15, and IL-18), and Th2 cytokine (IL-4, IL-5 and IL-10) genes. We observed enhancement of antigen-specific humoral response with the co-delivery of Th2 cytokine genes IL-4, IL-5, and IL-10 as well as those of IL-2 and IL-18. A dramatic increase in antigen-specific T helper cell proliferation was seen with IL-2 and TNF-alpha gene co-injections. In addition, we observed a significant enhancement of the cytotoxic response with the co-administration of TNF-alpha and IL-15 genes with HIV-1 DNA immunogens. These increases in CTL response were both MHC class I restricted and CD8+ T cell dependent. Together with earlier reports on the utility of co-immunizing using immunologically important molecules together with DNA immunogens, we demonstrate the potential of this strategy as an important tool for the development of more rationally designed vaccines.

AIDS Vaccines↗

PubMed1998

Oral cavity and pharynx.

Imaging of the oral cavity and pharynx often is required in three settings: assessment of an inflammatory mass in association with odontogenic, tonsillar, or pharyngeal infections; determination of the cause of a submucosal mass; and staging of squamous-cell carcinomas. Spread of infection from the oral cavity and pharynx can lead to abscesses in the masticatory space, the retropharyngeal compartment, and in a parapharyngeal location. Submucosal masses include congenital cysts (thyroglossal and dermoid), benign neoplasms (hemangioma, schwannomas, pleomorphic adenomas juvenile angiofibromas), inflammatory cysts (mucous retention cysts, ranulas), and pseudotumors (osteophytes, carotid arteries). Staging of squamous-cell carcinomas must focus on deep invasion, spread to the brain, nerves, mandible, prevertebral muscle, and pre-epiglottic fat.

Abscess↗

PubMed1998

Engineering DNA vaccines via co-delivery of co-stimulatory molecule genes.

DNA immunization has been investigated as a potential immunization strategy against infectious diseases and cancer. To enhance a DNA vaccine's ability to induce CTL response in vivo, we co-administered CD80 and CD86 expression cassettes along with HIV-1 immunogens. This manipulation resulted in a dramatic increase in MHC class I-restricted and CD8+ T-cell-dependent CTL responses in both mice and chimpanzees. This strategy of engineering vaccine producing cells to be more efficient T-cell activators could be an important tool for optimizing antigen-specific T-cell-mediated immune responses in the pursuit of more rationally designed vaccines and immune therapies.

Amino Acid Sequence↗

PubMed1998

Coadministration of IL-12 or IL-10 expression cassettes drives immune responses toward a Th1 phenotype.

Cytokines are important regulators of the immune response. They influence immune expression, the development of immunologic memory, and regulation of antigen-specific and nonspecific immune activation as well as allergic responses. In a model system in mice, we have studied the effect of plasmids expressing interleukin (IL)-10 or IL-12 on the modulation of antigen-specific responses. Coadministration of IL-12 or IL-10 genes with DNA immunogens directed the antigen-specific immune response toward a T helper (Th1)-type immunity. In addition to the modulation of antigen-specific immune responses, we studied the induction of delayed-type hypersensitivity (DTH) to contact allergens as an in vivo model of the Th1 response. We found that IL-12 and IL-10 gene-containing plasmids, and not the bacterial plasmid alone, upregulate this response. Our cytokine gene delivery technique demonstrates an important level of control of the magnitude and direction of induced immune responses and could be advantageous in a wide variety of immunotherapeutic strategies.

Animals↗

PubMed1998

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

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

Adipose Tissue↗

PubMed1997

Engineering of in vivo immune responses to DNA immunization via codelivery of costimulatory molecule genes.

Nucleic acid immunization is a novel vaccination technique to induce antigen-specific immune responses. We have developed expression cassettes for cell surface markers CD80 and CD86, two functionally related costimulatory molecules that play an important role in the induction of T cell-mediated immune responses. Coimmunization of these expression plasmids, along with plasmid DNA encoding for HIV-1 antigens, did not result in any significant change in the humoral response; however, we observed a dramatic increase in cytotoxic T-lymphocyte (CTL) induction as well as T-helper cell proliferation after the coadministration of CD86 genes. In contrast, coimmunization with a CD80 expression cassette resulted in a minor, but positive increase in T-helper cell or CTL responses. This strategy may be of value for the generation of rationally designed vaccines and immune therapeutics.

Animals↗

PubMed1997

Synovial sarcomas of the head and neck: MR findings.

OBJECTIVE: MR images of six synovial sarcomas of the head and neck were evaluated to determine their characteristic sites of origin, size, extent, intensity, and contrast enhancement. It was hoped that specific MR characteristics could be defined to suggest this entity. CONCLUSION: A nonmucosal head and neck mass that is isointense to gray matter on T1-weighted images and is well defined yet heterogeneous, with septations, hemorrhage, cysts, calcification, or multilocularity, should raise suspicion of a synovial sarcoma. Because the appearance of synovial sarcomas varies and other masses may appear similar, no specific imaging characteristics define the entity.

Adult↗

PubMed1997

Can radiologists accurately predict preepiglottic space invasion with MR imaging?

OBJECTIVE: The purpose of this study was to evaluate whether observers of MR imaging can accurately predict invasion of the preepiglottic fat (PEF) in patients with oropharyngeal and supraglottic laryngeal squamous cell carcinoma. MATERIALS AND METHODS: For 41 patients with pathologically proven squamous cell carcinoma of the oropharynx and supraglottic larynx, we retrospectively analyzed their MR images for the presence or absence of PEF neoplastic invasion. Unenhanced T1-weighted, fat-suppressed T2-weighted, and contrast-enhanced fat-suppressed T1-weighted scans were analyzed independently by two neuroradiologists who were unaware of the surgical findings. Proof of diagnosis was determined by pathologic analysis, intraoperative assessment, or both. RESULTS: Sixteen patients had neoplastic infiltration of the PEF. All infiltration was correctly predicted by the two observers of MR imaging, resulting in a sensitivity of 100%. Twenty-five patients had no invasion of the PEF by pathologic or surgical evaluation or both. Of these patients, negative findings were correctly predicted on MR imaging in 21 patients, whereas positive findings were incorrectly predicted on MR imaging in the remaining four patients, resulting in a specificity of 84% and an accuracy of 90%. In two of the four false-positive cases, effacement of the fat in the preepiglottic space by large tumors was mistaken for invasion. In a third patient, spread to the paraglottic space was mistaken for PEF extension. In the fourth false-positive case, glandular tissue along the ventral epiglottis may have been mistaken for tumor. The observers believed that unenhanced sagittal and axial T1-weighted scans were particularly useful because fat saturation artifacts may degrade T2-weighted and contrast-enhanced T1-weighted scans. CONCLUSION: Unenhanced T1-weighted MR images are highly sensitive for neoplastic infiltration of the preepiglottic space in patients with oropharyngeal and supraglottic laryngeal carcinoma who are at risk for such spread. Identification of PEF invasion is important because it affects prognosis and may affect surgical management.

Adipose Tissue↗

PubMed1997

Heterotopic brain in the pterygopalatine fossa.

Heterotopic brain outside the cranial vault is uncommon. It occurs most frequently in the nasal region, although rests elsewhere in the aerodigestive tract have been reported. We describe a case of heterotopic brain in the pterygopalatine fossa.

Biopsy↗

PubMed1997

Adenoidal width and HIV factors.

PURPOSE: To determine the factors that correspond to adenoidal hypertrophy, often prominent in human immunodeficiency virus (HIV)-positive patients. METHODS: The sagittal T1-weighted MR images of 21 HIV-positive patients (age range, 25 to 50 years; mean, 37 years) and 21 healthy control subjects (age range, 24 to 55 years; mean, 35 years) were reviewed blindly and independently by two radiologists who measured the maximal dimension of the nasopharyngeal lymphoid tissue. Twenty-six additional HIV-positive patients were combined with the original 21 HIV-positive patients, and the hematologic studies of these 47 patients were compared with the adenoidal measurements to assess whether a relationship existed between nasopharyngeal prominence and hematocrit, white blood cell count, and CD4 count. RESULTS: Mean adenoidal width was 6.76 mm (SD, 5.82) in the HIV-positive population, but was only 3.36 mm (SD, 2.48) in the age-matched control group. Age and HIV status correlated with nasopharyngeal width measurements. No relationship between adenoidal width and hematocrit, CD4 count, or white blood cell count was evident. CONCLUSION: After correcting for age, we found that adenoidal lymphoid tissue is more abundant in HIV-positive persons than in control subjects. The hematologic ramifications of this finding remain uncertain.

Adenoids↗

PubMed1994

Solitary plasmacytoma of the mastoid bone presenting as coalescent mastoiditis.

Acute mastoiditis is a complication of acute otitis media that produces air cell opacification and coalescence on computed tomographic (CT) imaging. This appearance, however, is nonspecific and may be seen in patients with infection and tumor. Magnetic resonance imaging (MRI) can aid in differentiating the two on the basis of differences in tissue signal characteristics and by showing the presence or absence of an associated soft-tissue mass. In this report, we demonstrate the utility of MRI as a complementary imaging modality to CT in the diagnosis of a solitary plasmacytoma of the temporal bone that was initially thought to be coalescent mastoiditis.

Biopsy↗

PubMed1989

Evaluation of high-intensity therapeutic ultrasound irradiation in the treatment of experimental hepatoma.

A study evaluating the efficacy of high-intensity therapeutic ultrasound (HITU) as a treatment modality in experimental hepatoma is reported. Morris hepatoma (3924) 1 x 10(6) cells were transferred subcutaneously into 40 male ACI rats (weight, 150 to 200 g). Animals were divided into four experimental groups: group 1 (n = 10) consisted of untreated controls; group 2 (n = 10) received intraperitoneal cyclophosphamide 50 mg/kg as a single dose; group 3 (n = 10) underwent HITU only; and group 4 (n = 10) received both chemotherapy (as in group 2) and HITU (as in group 3). HITU was administered with a 5.5-cm diameter 4-MHz quartz transducer creating a continuous wave with 400 W/cm2 focal intensity. The entire tumor was irradiated in 1-mm increments (horizontal and vertical) using treatment cycles of 4 seconds on and 11 seconds off. Total body weight and tumor volume were measured on the day of treatment, and 4 weeks later. At 4 weeks, the animals were killed, the tumor was excised and weighed, and tumor volume was determined. Tumor volume in all treated animals (groups 2, 3 and 4) was significantly smaller than in controls (P less than .001) at 4 weeks, and tumor volume for animals in group 4 was significantly smaller than for those in groups 2 and 3 (P less than .01). These data indicate that HITU significantly reduces tumor size when compared with control rats with Morris hepatoma. A synergistic effect of chemotherapy and HITU was observed and resulted in an enhanced tumor response and reduction of tumor size.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Advanced oropharyngeal carcinoma treated with surgery and radiotherapy: oncologic outcome and functional assessment.

INTRODUCTION/PURPOSE: Surgery and postoperative radiotherapy (XRT) is a standard therapy for locally advanced resectable oropharyngeal carcinoma. This maximizes local-regional control, but does not address the potential for occult distant metastases. Additionally, some patients may suffer poor functional outcome after this intensive local therapy. This report reviews our institutional experience with modern radical surgery and XRT for this disease. METHODS: A retrospective chart review was performed on 51 consecutive patients treated from 1991 to 1997 at the University of Pennsylvania with radical surgery and postoperative XRT. This study included patients with locally advanced, stage III/IV (exclusive of T1-2N1) squamous carcinoma of the oropharynx. All patients had a good performance status (ECOG 0-1). Patients who received adjuvant chemotherapy were excluded. No patient had gross residual disease after surgery; the median XRT dose was 63.7 Gy. Survival, local-regional control (LRC), and freedom from distant metastases (DM) were calculated actuarially. In patients who remained free of disease, functional status was determined using the List Performance Status Scale (PSS). RESULTS: With a median follow-up in surviving patients of 34 months, the 3-year actuarial overall survival was 51%. The 3-year LRC was 73%, and the freedom from DM was 69%. The most significant factor predicting for failure was the number of pathologically positive nodes (P <.001 for survival and DM; P =.003 for LRC). In 29 patients who were evaluable for the List PSS, the mean normalcy-of-diet score was 48; the mean eating-in-public score was 53; and the mean understandability-of-speech score was 75. There was a trend toward better PSS scores in patients with T1-2 tumors versus T3-4 tumors, although this did not reach statistical significance. CONCLUSIONS: Surgery and postoperative XRT offer relatively good LRC and moderate overall survival rates. Results, however, remain suboptimal, particularly with respect to the risk of DM and the functional outcome. These data provide a baseline for comparison with maturing results from multimodality trials in which radical surgery is not used in all patients with locally advanced oropharyngeal carcinoma.

Adult↗

PubMedDate not supplied

Malignant tumors of the nose and paranasal sinuses: hospital of the University of Pennsylvania experience 1990-1997.

We reviewed our experience with sinonasal malignancies, which comprise less than 1% of all cancers, in order to determine the spectrum of disease and outcome after treatment. The medical records of 48 patients with sinonasal malignancies treated between 1990-1997 were reviewed for epidemiologic characteristics, tumor location and histology, treatment modalities, and tumor recurrence. Mean age was 58.5 years and 46% were male. Multiple sites of origin were common, including maxillary sinus (83%), ethmoid sinus (35%), and nasal cavity (40%). The histologic spectrum included squamous cell carcinoma (46%), adenoid cystic carcinoma (6%), and miscellaneous others (48%). Treatment included surgery and adjuvant radiotherapy (XRT) (58%), surgery alone (27%), XRT and chemotherapy (6%), surgery and chemotherapy (4%), and XRT alone (4%). Mean follow-up was 15 months (range 2-58). Recurrence was evident in nine patients (19%), 3 (33%) of whom had prior treatment before presenting to HUP. Of the six who recurred after initial treatment at HUP, five (83.3%) were treated with surgery and XRT and one (16.7%) was treated with surgery alone. Of the three that recurred after undergoing attempts at salvage (prior treatment and then treatment at HUP), one had received surgery alone followed by surgery and XRT, one had surgery and XRT followed by surgery and one had XRT followed by surgery alone. Our experience reveals surgery and XRT to be the modality of choice, particularly for advanced tumors, whereas surgery alone may be sufficient for small, well localized tumors. Neoadjuvant chemotherapy may offer improved local control; the future role of endoscopic surgery warrants further investigation.

Adult↗