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Biomedical subjects

J P Shah

Publications and source records attributed to J P Shah.

At least 19 recordsLinked to original sources
PubMed2005

Continuous negative extrathoracic pressure or continuous positive airway pressure for acute hypoxemic respiratory failure in children.

BACKGROUND: Acute hypoxemic respiratory failure (AHRF) is an important cause of mortality and morbidity in the pediatric age group. Positive pressure ventilation is currently the standard of care, though is known to be associated with complications. Continuous negative extrathoracic pressure ventilation (CNEP) or continuous positive airway pressure ventilation delivered via non-invasive approaches (Ni-CPAP) have shown certain beneficial effects in animal and uncontrolled human studies. OBJECTIVES: The primary objective of this review was to assess the effectiveness of CNEP and Ni-CPAP in pediatric patients with AHRF due to non-cardiogenic causes. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005); MEDLINE (January 1966 to March 2005); EMBASE (1980 to March 2005); CINAHL (1982 to March 2005); published abstracts from the meetings of the American Thoracic Society and Pediatric Critical Care Meetings (1992 to 2005); and bibliographies of identified articles and asking the experts in the field. SELECTION CRITERIA: Randomized or quasi-randomized clinical trials of either CNEP or Ni-CPAP versus standard therapy (positive pressure ventilation) involving children (at least 1 month old and less than 18 years of age at the time of randomization) who met the criteria for diagnosis of AHRF with at least one of the outcomes reported were included. DATA COLLECTION AND ANALYSIS: The methodological quality of included study was assessed using the following criteria: concealment of randomization, blinding of intervention, completeness of follow up and blinding of outcome measurements. Data on relevant outcomes were abstracted and the effect size was estimated by calculating relative risk (RR) with 95% confidence intervals (CI) and risk difference (95% CI). MAIN RESULTS: One eligible study was identified which was published in abstract format. Thirty-three infants (18 in the control group and 15 in the CNEP group) with a clinical diagnosis of bronchiolitis and fraction of inspired oxygen (FiO(2))()greater than 40% were studied. There was reduction in the FiO(2) (less than 30% within one hour of initiation of therapy) in four patients in the CNEP group compared to none in the control group (RR 10.7, 95% CI 0.6 to 183.9). One infant required positive pressure ventilation and one infant required nasal CPAP in the control group while all infants in the CNEP group were managed without intubation (RR for both outcomes 0.40, 95% CI 0.02 to 9.06). AUTHORS' CONCLUSIONS IMPLICATION FOR PRACTICE: There is a lack of well designed, controlled experiments of noninvasive modes of respiratory support in children with AHRF. Implication for research: Reduction of in-hospital mortality is an important outcome and even a small reduction could be beneficial. Studies assessing other outcomes such as avoidance of intubation and its associated complications, reduction in hospital stay and improvement in patient comfort are also valuable in gauging the overall impact of these strategies.

Humans↗
PubMed2003

Continuous negative extrathoracic pressure or continuous positive airway pressure for acute hypoxemic respiratory failure in children.

BACKGROUND: Acute hypoxemic respiratory failure (AHRF) is an important cause of mortality and morbidity in the pediatric age group. Despite varied etiologies and different population characteristics the aims of therapy are to achieve adequate oxygenation and ventilation. Positive pressure ventilation is currently the standard of care. It is ordinarily provided by intubation and mechanical ventilation, which is associated with a number of well recognized complications. Continuous negative extrathoracic pressure ventilation (CNEP) or continuous positive airway pressure ventilation delivered via non-invasive approaches (Ni-CPAP) have shown certain beneficial effects in animal and uncontrolled human studies. In a systematic review of studies involving neonates, continuous distending pressure using either CNEP or CPAP (applied via face mask) was associated with reduction in mortality but with an increased incidence of pneumothoraces, in neonates. OBJECTIVES: The primary objective of this review was to assess the effectiveness of CNEP and Ni-CPAP in pediatric patients with AHRF due to non-cardiogenic causes. SEARCH STRATEGY: A literature search was performed using following databases: Cochrane Central Register of Controlled Trials (December 2002); MEDLINE (January 1966 to December 2002); EMBASE (1980 to December 2002); CINAHL (1982 to December 2002); published abstracts from the meetings of the American Thoracic Society and Pediatric Critical Care Meetings (1992 to 2001); and bibliographies of identified articles and asking the experts in the field. SELECTION CRITERIA: Selection criteria applied to the clinical trials were: the population were children (at least 1 month old and less than 18 years of age at the time of randomization); patients met the criteria for diagnosis of AHRF; intervention was either CNEP or Ni-CPAP versus standard therapy (positive pressure ventilation); the trial was randomized or quasi-randomized; and at least one of the primary or secondary outcomes were reported. DATA COLLECTION AND ANALYSIS: The methodological quality of included study was assessed using the following criteria: concealment of randomization, blinding of intervention, completeness of follow up and blinding of outcome measurements. Data on relevant outcomes were abstracted and the effect size was estimated by calculating relative risk (RR) with 95% confidence intervals (CI) and risk difference (95% CI). MAIN RESULTS: One eligible study was identified which was published in abstract format. Thirty three infants (18 in the control group and 15 in the CNEP group) with a clinical diagnosis of bronchiolitis and oxygen requirement of greater than 40% were studied. There was reduction in the oxygen requirement (less than 30% within one hour of initiation of therapy) in four patients in the CNEP group compared to none in the control group (typical RR 10.7, 95% CI 0.6, 183.9). One infant required positive pressure ventilation and one infant required nasal CPAP in the control group while all infants in the CNEP group were managed without intubation (typical RR for both outcomes 0.40, 95% CI 0.02, 9.06). REVIEWER'S CONCLUSIONS IMPLICATION FOR PRACTICE: There is a lack of well designed, large controlled experiments comparing use of noninvasive modes of respiratory support in children with AHRF. Uncontrolled evidence of reduction in the intubation and hospital stay needs confirmation in proper studies evaluating risks involved with these practices. Implication for research: It is unlikely that CNEP or Ni-CPAP will have significant impact on mortality in AHRF, however, even a small reduction may be very important. Studies assessing other outcomes such as avoidance of intubation and its associated complications, reduction in hospital stay and improvement in patient comfort are also valuable in assessing the overall impact of these strategies.

Humans↗
PubMed2002

Diagnostic and prognostic value of [(18)F]fluorodeoxyglucose positron emission tomography for recurrent head and neck squamous cell carcinoma.

PURPOSE: Patients with recurrent head and neck squamous cell carcinoma (HNSCC) present a diagnostic and therapeutic challenge. We evaluated the diagnostic accuracy and prognostic value of [(18)F]fluorodeoxyglucose positron emission tomography (PET) in this patient population. PATIENTS AND METHODS: We performed a retrospective review of 143 patients with previously treated HNSCC who underwent 181 PET scans at our institution from May 1996 through April 2001 to detect recurrent disease. Disease recurrence within 6 months was used as the gold standard for assessing true disease status at PET. RESULTS: With equivocal sites considered positive, the sensitivity and specificity of PET for detecting recurrence overall were 96% and 72%, respectively. PET was highly sensitive and specific at regional and distant sites. At local sites, sensitivity was high, but specificity was lower because of false-positive findings. One fifth of all false-positive PET scans occurred at sites of known inflammation or infection. The area under the curve for a receiver operator characteristic curve on the basis of standardized uptake value (SUV) was 0.882 +/- 0.025. PET interpretation, SUV, and physical examination were independent predictors of relapse-free and overall survival in a time-dependent, multivariate proportional hazards model. An increase in SUV by one unit increased the relative risk (RR) of relapse by 11% and the RR of death by 14%. A positive PET interpretation increased the RR of relapse by four-fold and the RR of death by seven-fold. CONCLUSION: PET was a highly sensitive method of detecting recurrent HNSCC and provided important prognostic information for relapse-free and overall survival.

Adolescent↗
PubMed2001

Molecular cytogenetic characterization of head and neck squamous cell carcinoma and refinement of 3q amplification.

We applied a combination of molecular cytogenetic methods, including comparative genomic hybridization (CGH), spectral karyotyping (SKY), and fluorescence in situ hybridization, to characterize the genetic aberrations in a panel of 11 cell lines derived from head and neck squamous cell carcinoma and 1 cell line derived from premalignant oral epithelium. CGH identified recurrent chromosomal losses at 1p, 3p, 4, 8p, 10p, and 18q; gains at 3q, 5p, 8q, 9q, and 14q; and high-level amplification at 3q13, 3q25-q26, 5q22-q23, 7q21, 8q24, 11q13-q14, 12p13, 14q24, and 20q13.1. Several recurrent translocations including t(1;13)(q10;q10), t(13;13)(q10;q10), t(14;14)(q10;q10), i(8)(q10), and i(9)(q10) and breakpoint clusters at 1p11, 1q21, 3p11, 5q11, 5q13, 6q23, 8p11, 8q11, 9p13, 9q13, 10q11, 11q13, 13q10, 14q10, and 15q10 were identified by SKY. There was a good correlation between the number of aberrations identified by CGH and SKY (r = 0.69), and the analyses were both confirmatory and complementary in their assessment of genetic aberrations. Amplification at 3q26-q27 was identified in 42% of cases. Although SKY defined the derivation of 3q gain, the precise breakpoint remained unassigned. Positional cloning efforts directed at the amplified region at 3q26-q27 identified three highly overlapping nonchimeric yeast artificial chromosome clones containing the apex of amplification. The use of these yeast artificial chromosome clones as a probe for fluorescence in situ hybridization analysis allowed a detailed characterization and quantification of the 3q amplification and refinement of unassigned SKY breakpoints.

Carcinoma, Squamous Cell↗
PubMed2001

Hürthle cell carcinoma: a critical histopathologic appraisal.

PURPOSE: Controversy exists over the ability of morphology to predict the biologic behavior of Hürthle cell carcinoma. The aim of this study was to conduct a critical histopathologic review of Hürthle cell carcinoma and to correlate morphologic parameters with clinical outcome. PATIENTS AND METHODS: Patients with histologically confirmed Hürthle cell carcinoma treated between 1940 and 2000 form the basis of this study. Adenomas were excluded. Tumors of unknown malignant behavior ([UMB] n = 17) had solid growth pattern, incomplete capsular invasion (Ci), or both but no vascular invasion (Vi). Minimally invasive carcinomas ([MIC] n = 23) had one focus of intra- or extracapsular Vi, one focus of complete Ci, or both. Widely invasive carcinomas ([WIC] n = 33) demonstrated more than one focus of Vi, more than one focus of Ci, or both. The primary end points were relapse-free survival (RFS) and disease-specific survival (DSS). Rates of recurrence/death were estimated by Kaplan-Meier method. The univariate influence of prognostic factors on end points was analyzed by log-rank test, and multivariate analysis was performed by Cox regression. RESULTS: Median follow-up was 8 years. No patients with UMB or MIC relapsed or died of disease. Of WIC, 73% relapsed and 55% died of disease. Age, size, and extent of resection did not influence outcome. Adverse predictors of RFS and DSS among WIC were extrathyroidal extension, nodal metastasis, positive margin, and solid growth pattern (P <.05). Both Ci and Vi were associated with worse DSS (P <.05). On multivariate analysis, extrathyroidal extension and nodal metastases were independent predictors of outcome (P <.05). CONCLUSION: Patients with Hürthle cell carcinoma have a prognosis that is predicted by well-defined histomorphologic characteristics. Unlike differentiated thyroid cancer, nodal metastases predict a worse outcome in widely invasive Hürthle cell carcinoma, as does extrathyroidal extension.

Carcinoma↗
PubMed2001

Accelerated concomitant boost radiotherapy and chemotherapy for advanced nasopharyngeal carcinoma.

PURPOSE: To evaluate the feasibility and efficacy of concomitant boost radiotherapy (RT) plus cisplatin-based chemotherapy compared with standard fractionation RT for patients with advanced nasopharyngeal cancer. PATIENTS AND METHODS: From 1988 through 1999, 50 patients with American Joint Committee on Cancer stage II-IVb nasopharyngeal carcinoma were treated with 70-Gy concomitant boost RT (1.8 Gy/d, weeks 1 through 6; 1.6 Gy second daily fraction, weeks 5 through 6) and two cycles of concurrent cisplatin 100 mg/m(2) days 1 and 22. Thirty-seven patients also received three cycles of cisplatin-based adjuvant chemotherapy. These 50 patients were compared with a nonrandomized cohort of 51 patients with nasopharyngeal cancer treated with 70-Gy standard fractionation RT (1.8 Gy/d) without chemotherapy from 1988 through 1995. The groups were well matched for prognostic factors except stage, for which the concomitant boost RT/chemotherapy group was more advanced (54%, T3-4; 54%, N2-3; 44%, stage IV) compared with the standard RT group (31%, T3-4, P =.03; 22%, N2-3, P <.001; 20%, stage IV, P <.01). RESULTS: With a median follow-up of 42 months (range, 12 to 129 months), the 3-year actuarial local control, progression-free survival, and survival rates were 89% v 74% (P <.01), 66% v 54% (P =.01), and 84% v 71% (P =.04) for the concomitant boost RT/chemotherapy group and the standard RT patients, respectively. Acute grade 3 mucositis was more prevalent with combined therapy, 84% v 43% (P <.001), resulting in a higher rate of temporary gastrostomy tube placement, 46% v 20% (P <.01). CONCLUSION: Concomitant boost RT with cisplatin-based chemotherapy is feasible and improves local-regional control as well as survival for patients with advanced nasopharyngeal cancer compared with standard RT alone.

Adolescent↗
PubMed2001

Cytokine gene transfer enhances herpes oncolytic therapy in murine squamous cell carcinoma.

Replication-competent, attenuated herpes simplex viruses (HSV) have been demonstrated to be effective oncolytic agents in a variety of malignant tumors. Cytokine gene transfer has also been used as immunomodulatory therapy for cancer. To test the utility of combining these two approaches, two oncolytic HSV vectors (NV1034 and NV1042) were designed to express the murine GM-CSF and murine IL-12 genes, respectively. These cytokine-carrying variants were compared with the analogous non-cytokine-carrying control virus (NV1023) in the treatment of murine SCC VII squamous cell carcinoma. All three viruses demonstrated similar infection efficiency, viral replication, and cytotoxicity in vitro. SCC VII cells infected by NV1034 and NV1042 effectively produced GM-CSF and IL-12, respectively. In an SCC VII subcutaneous flank tumor model in immunocompetent C3H/HeJ mice, intratumoral injection with each virus caused a significant reduction in tumor volume compared with saline injections. The NV1042-treated tumors showed a striking reduction in tumor volume compared with the NV1023- and NV1034-treated tumors. On subsequent rechallenge in the contralateral flank with SCC VII cells, 57% of animals treated with NV1042 failed to develop tumors, in comparison with 14% of animals treated with NV1023 or NV1034, and 0% of naive animals. The increased antitumor efficacy seen with NV1042 in comparison with NV1023 and NV1034 was abrogated by CD4(+) and CD8(+) lymphocyte depletion. NV1042 is a novel, attenuated, oncolytic herpesvirus that effectively expresses IL-12 and elicits a T lymphocyte-mediated antitumor immune response against murine squamous cell carcinoma. Such combined oncolytic and immunomodulatory strategies hold promise in the treatment of cancer.

Animals↗
PubMed2001

Growth and differentiation of PC6 cells: the effects of pulsed electromagnetic fields (PEMF).

Previous studies in our laboratory showed that neurite outgrowth in vitro and nerve regeneration in vivo were stimulated by 2 Hz, 0.3 mT (3 G) pulsed electromagnetic fields (PEMF). To learn more about the effects of PEMF on nerve cells, we exposed PC6 cells, a standard neuronal-like cell model, to the same pulsed electromagnetic fields for 2 h/day for 2 days and asked whether two different cell processes, proliferation and differentiation, were affected. The cells were also treated with a differentiating agent, nerve growth factor (NGF), to further define any interactive effects. We found that proliferation was unaffected by either PEMF or NGF alone or in combination. Differentiation, expressed as neurite outgrowth, was strongly upregulated with NGF, but this NGF response was significantly depressed in cells treated with PEMF.

Animals↗
PubMed2001

Effective treatment of head and neck squamous cell carcinoma by an oncolytic herpes simplex virus.

BACKGROUND: The prognosis of patients with advanced or recurrent head and neck squamous cell carcinoma remains poor despite refinements in multimodality therapies. This study evaluates the efficacy of a replication-competent, attenuated, oncolytic herpes simplex virus, NV1020, as a novel agent in the treatment of human head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: Five different HNSCC lines were exposed to NV1020 in vitro at varying viral concentrations. The ability of the virus to lyse and replicate within these cancer cells in vitro was determined by cytotoxicity assay and plaque assay, respectively. Three HNSCC lines were grown in the subcutaneous flanks of athymic nude mice and treated with an intratumoral injection of NV1020 or saline as a control. Tumor dimensions were subsequently measured at serial time points and tumor volumes were calculated. Herpes simplex virus (HSV)-1 immunohistochemistry was performed on excised tumors to determine the efficacy of in vivo tumor infection by NV1020. RESULTS: NV1020 was highly cytotoxic in vitro to all five human HNSCC lines at a concentration of one infectious viral particle per cancer cell, and had variable cytotoxicity at a 100-fold lower concentration. Viral replication in vitro by NV1020 was efficient in four of five HNSCC lines with a greater than 200-fold increase in viral titers. Flank tumors treated with intratumoral injections of NV1020 resulted in significant regression of all tested HNSCC lines. HSV-1 immunohistochemistry of excised flank tumors treated with NV1020 demonstrated positive cytoplasmic staining and areas of tumor necrosis at 24 hours after injection. CONCLUSIONS: NV1020 is an oncolytic HSV that displays efficient replication and oncolysis in human HNSCC lines in vitro. Injection of NV1020 into murine flank tumors demonstrated effective tumor regression. Treatment of HNSCC with NV1020 is a promising form of therapy with potential clinical applicability in humans.

Animals↗
PubMed2000

Initial results from a prospective cohort study of 5583 cases of thyroid carcinoma treated in the united states during 1996. U.S. and German Thyroid Cancer Study Group. An American College of Surgeons Commission on Cancer Patient Care Evaluation study.

BACKGROUND: The American College of Surgeons Commission on Cancer (CoC) has conducted national Patient Care Evaluation (PCE) studies since 1976. METHODS: Over 1500 hospitals with CoC-approved cancer programs were invited to participate in this prospective cohort study of U.S. thyroid carcinoma cases treated in 1996. Follow-up will be conducted through the National Cancer Data Base. RESULTS: Of the 5584 cases of thyroid carcinoma, 81% were papillary, 10% follicular, 3.6% Hürthle cell, 0.5% familial medullary, 2.7% sporadic medullary, and 1.7% undifferentiated/anaplastic. Demographics and suspected risk factors were analyzed. Fine-needle aspiration of the thyroid gland (53%) or a neck lymph node (7%), thyroid nuclear scan (39%), and ultrasound (38%) constituted the most frequently utilized diagnostic modalities. The vast majority of patients with differentiated thyroid carcinoma presented with American Joint Committee on Cancer Stage I and II disease and relatively small tumors. For all histologies, near-total or total thyroidectomy constituted the dominant surgical treatment. No lymph nodes were examined in a substantial proportion of cases. Residual tumor after the surgical event could be documented in 11% of cases, hypocalcemia in 10% of cases, and recurrent laryngeal nerve injury in 1.3% of cases. Complications were most frequently associated with total thyroidectomy combined with lymph node dissection. Thirty-day mortality was 0.3%; when undifferentiated/anaplastic cancer cases were eliminated, it decreased to 0.2%. Adjuvant treatment, probably underreported in this study, consisted of hormonal suppression (50% overall) and radioiodine (50% overall). CONCLUSIONS: In addition to offering information concerning risk factors and symptoms, the current PCE study compliments the survival information from previous NCDB reports and offers a surveillance snapshot of current management of thyroid carcinoma in the U.S. Identified opportunities for improvement of care include 1) more frequent use of fine-needle aspiration cytology in making a diagnosis; 2) more frequent use of laryngoscopy in evaluating patients preoperatively, especially those with voice change; and 3) improved lymph node resection and analysis to improve staging and, in some situations, outcomes.

Adenocarcinoma, Follicular↗
PubMed2000

Desmoid tumors of the head and neck--a clinical study of a rare entity.

BACKGROUND: Desmoid tumors are are, nonmalignant neoplasms that show locally aggressive growth but lack the potential to metastasize. Common anatomic sites include the extremity, abdominal wall, and mesentery. Little is reported about clinical features and outcome of desmoid tumors of the head and neck. METHODS: Twenty-one patients with desmoid tumors of the head and neck treated at MSKCC between July 1982 and June 1999 were identified from our inpatient tumor database. All patients underwent surgical resection and were prospectively followed. Clinicopathologic features and treatment modalities were evaluated. RESULTS: Patient age at diagnosis was 22 to 76 years, with a female-male ratio of 16:5. Most tumors were located in the supraclavicular fossa or the muscles of the neck (n = 19). Patients most commonly had a painless mass (n = 13) or neurologic symptoms including pain or neurologic deficit (n = 8). Extent of resection was limited to the tumor in nine patients. In the other 12, structures including the accessory or phrenic nerve, parts of the brachial plexus, or bony structures were resected. Persistent neurologic or functional deficits after surgery were noted in 12 patients. Five of 21 patients had recurrences (24%). Eleven patients received radiation therapy. In this small population, no obvious benefit for patients receiving radiation vs patients who were not irradiated, regardless of their surgical margin status, was seen. Treatment for recurrence was re-resection or re-resection plus radiation. Eighteen patients remained free of disease after treatment, two patient have stable disease and one died of other causes. No patients died of their disease. CONCLUSIONS: Desmoid tumors of the head and neck are rare, fibrous neoplasms with a good prognosis but significant morbidity. Function-preserving surgery should be a primary goal to minimize morbidity. In this small group of patients, the benefits of radiation therapy in patients with positive margins could not be clearly demonstrated and should be balanced against radiation-related morbidity.

Adult↗
PubMed2000

Dermatofibrosarcoma protuberans of the head and neck.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) of the head and neck is a rare, locally infiltrative, low-grade sarcoma. This study defines the clinical behavior of DFSP, evaluates the role of frozen section analysis, and identifies factors that predict local control. METHODS: Hospital records and pathological slides were reviewed for 33 patients with pathologically confirmed head and neck DFSP treated at Memorial Sloan-Kettering Cancer Center between 1964 and 1999. Factors were analyzed by using Fisher's exact or chi2 tests. RESULTS: For 21 primary and 12 recurrent patients, median age and tumor size at presentation was 39 years and 2.0 cm, respectively. Thirty-two (97%) patients were alive at a median follow-up of 82 months. Three patients recurred locally, all with smaller than 2-cm resection margins. Deep tumors were more likely to have a margin-positive resection than superficial lesions (P = .03). Gross margin 2 cm or more was a significant predictor of a negative histological margin (P<.001). There was a trend toward improved recurrence-free survival for tumors treated with wide (> or =2 cm) margin resection (P = .059). Accuracy, sensitivity, specificity, and false negative rates of frozen section were 80%, 43%, 100%, and 57%, respectively. CONCLUSIONS: Wide margin resection of head and neck DFSP predicts negative histological margins and impacts favorably on local recurrence-free survival. Frozen section analysis does not assess resection margins accurately.

Adult↗
PubMed2000

Epstein-Barr virus in squamous carcinoma of the anterior nasal cavity.

Squamous carcinoma is the most common malignancy of the head and neck, but it rarely occurs in the nasal vestibule. Epstein-Barr virus (EBV) has been detected in and is causally linked to various head and neck tumors, particularly nasopharyngeal carcinoma. The possible role of EBV in squamous carcinoma of the anterior nasal cavity, particularly of the nasal vestibule, has not been previously investigated. Histologic sections from 17 patients with nasal vestibular squamous carcinoma were examined. Material for EBV detection by immunohistochemistry and by in situ hybridization was available in 15 of the 17 cases. The study group consisted of eight men and nine women ranging in age from 40 to 82 years (mean age, 64 years). None of the patients was of Asian descent. The squamous carcinomas were graded as well differentiated (one case), moderately differentiated (11 cases), and poorly differentiated (five cases). Fourteen patients were smokers; the history of smoking ranged from 20 to 60 pack-years. Treatment modalities included surgical resection, radiation, chemotherapy, or a combined approach. The clinical follow-up periods ranged from 7 months to 16 years. Three patients developed metastases, one of whom died of disease after 1 year. Epstein-Barr virus was not detected in any of the 15 of 17 cases tested by either immunohistochemistry or by in situ hybridization. Squamous carcinoma of the nasal vestibule is an uncommon cancer that is not causally related to EBV.

Adult↗
PubMed2000

Combination gene therapy using multiple immunomodulatory genes transferred by a defective infectious single-cycle herpes virus in squamous cell cancer.

Herpes simplex type 2-defective infectious single-cycle (DISC) viruses are attenuated viruses that were originally produced as viral vaccines; however, these viruses are also efficient gene transfer vehicles. The main goals of this study were to examine determinants of the gene transfer by using DISC virus for squamous cancer and to evaluate the antitumoral efficacy of vaccination with tumor cells modified by DISC viruses carrying a combination of immunomodulatory genes (interleukin-2 (IL-2), granulocyte-macrophage colony-stimulating factor (GM-CSF), B7-1) in a model of squamous cell cancer (SCCVII) in C3H/HeJ mice. SCCVII cells transduced by DISC viruses (multiplicity of infection of 10) carrying the IL-2 or GM-CSF gene produced nanogram quantities of IL-2 or GM-CSF per 10(6) cells. Irradiated (5,000 cGy, 10,000 cGy) cells secreted levels of GM-CSF or IL-2 that were comparable with nonirradiated cells. In vivo vaccination using tumor cells transduced ex vivo with DISC-IL2 or DISC-GMCSF resulted in protection against subsequent tumor challenge (P < .01), with DISC-GMCSF-transduced, irradiated tumor cells showing the greatest effects (P < .001). Marked growth arrest also was noted in established tumors after direct injection of DISC-GMCSF (P < .001). These data demonstrate that (a) DISC virus is capable of efficient gene transfer, (b) GM-CSF-secreting genetically modified tumor vaccine protects against tumor cell challenge and suppresses tumor growth, and (c) intratumoral injection of DISC-GMCSF significantly suppresses the growth of established tumors. These results not only confirm clinically relevant gene transfer but also demonstrate that the gene transfer is an effective anti-cancer therapy.

Animals↗
PubMed2000

Screening for genetic aberrations in papillary thyroid cancer by using comparative genomic hybridization.

BACKGROUND: Determination of the genetic composition of papillary thyroid cancers may help explain differences in observed clinical behavior. Comparative genomic hybridization (CGH) is a novel molecular cytogenetic assay that allows simultaneous detection of gains, losses, and amplification of genetic information, making it an ideal screening tool. The aim of this study was to identify genetic aberrations occurring in papillary thyroid cancers by using CGH analysis. METHODS: CGH analysis was performed on 21 individual cases of papillary thyroid cancers. Nonparametric statistical comparisons were performed with the Fisher exact test. RESULTS: Genetic abnormalities were identified by CGH in 10 of 21 cases (48%). A recurrent pattern of aberrations was seen in cases where genetic changes were detected, involving losses at chromosome arms 1p and 9q and chromosomes 17, 19, and 22, and gains at chromosome 4 and chromosome arms 5q, 6q, 9q, and 13q. The loss of chromosome 22 was unique to younger patients (P =.05) and was associated with a higher rate of regional lymphatic metastasis (19% vs 80%, P =.02). CONCLUSIONS: Two genetically unique groups of patients were identified by using CGH analysis. One group had no detectable aberrations; the other had a recurrent pattern of aberrations, localizing to the identical chromosomal loci. This pattern of aberrations suggests that the involved loci may contain genes important in thyroid carcinogenesis. The clinical significance of the presence of copy number changes detected by CGH needs to be determined. In addition, molecular cloning of involved genes in each of the aberrations is warranted.

Adolescent↗
PubMed2000

Genome-wide screening for radiation response factors in head and neck cancer.

INTRODUCTION: Radiation therapy is an integral part of the treatment of head and neck cancer. Factors predicting radiation response are ill defined. The aim of this study was to identify genetic aberrations associated with radiation response in cell lines derived from head and neck squamous cell carcinomas (HNSCC) using comparative genomic hybridization (CGH) for genome-wide screening. METHODS: Five cell lines derived from HNSCC were subjected to a single course of radiation (400 cGy) in parallel with a similarly handled, untreated control. Cellular response to radiation was determined on posttreatment days 1, 2, 3, 4, and 5 using a cell viability assay (MTT assay). Radiation response was defined as 35% or greater decrease in cell survival relative to control. Tumor doubling time was determined by cell counts performed at day 0 and 1 for each cell line. All experiments were done in quadruplicate. CGH analysis was performed by differentially labeling DNA from tumor and normal tissue with fluorescent agents. The labeled DNAs were simultaneously hybridized to normal metaphase chromosomes. Image analysis for fluorescence intensity along the entire length of each metaphase chromosome allowed generation of a color ratio, which was used to detect copy number changes. RESULTS: Radioresistance was identified in two of five cell lines. The tumor doubling time was not a predictor of radiation response. CGH identified a complex pattern of aberrations, with gain of 3q common to all cell lines. The number of genetic aberration was higher in radiation-sensitive cell lines than in radiation-resistant ones. No recurrent aberrations were unique to the radiation-resistant cell lines. Recurrent gains at 7p and 17q and losses at 5q, 7q, and 18q were unique to the radiation-sensitive cell lines. CONCLUSIONS: The number of aberrations identified by CGH analysis may be a predictor of radiation response. A large study of primary tumors is warranted to confirm this association and identify specific genetic aberrations associated with radiation response.

Carcinoma, Squamous Cell↗
PubMed2000

Basaloid squamous cell carcinoma of the head and neck.

OBJECTIVE/HYPOTHESIS: Basaloid squamous cell carcinoma (BSCC), an uncommon tumor with predilection for the upper aerodigestive tract, is a distinct variant of squamous carcinoma, because of its unique histological features and ominous clinical behavior. This study reviews the experience in treating BSCC from two institutions. STUDY DESIGN: Retrospective. METHODS: H&E-stained sections from 20 patients with BSCC of the head and neck were reviewed and clinical follow-up was obtained for all patients. RESULTS: The study group consisted of 14 male and 6 female patients. Their ages ranged from 43 to 85 years, with a mean age of 62 years. Sites of origin included the larynx (4), tongue (3), pyriform sinus (3), nose (2), floor of mouth (2), mastoid (1), tonsil (1), epiglottis (1), nasopharynx (1), trachea (1), and palate (1). Pain was the most common presenting symptom (5 cases), followed by hoarseness and bleeding (3 cases each). Tobacco and alcohol abuse was noted in 17 patients. Treatment modalities included surgery with or without chemotherapy or radiotherapy in 13 patients, chemotherapy with irradiation in 2, chemotherapy alone in 2, and radiotherapy alone in 3. Clinical follow-up revealed no evidence of disease in 11 patients. Four were alive with disease at the time of writing and five died of disease. CONCLUSION: BSCC is a highly aggressive malignant tumor that presents in elderly patients who have a history of abuse of tobacco or alcohol, or both. Greater number of patients must be studied and compared with age-matched and stage-matched controls of conventional squamous cell carcinoma to determine whether the poor clinical outcome is related more to high-stage presentation or to the tumor's high-grade malignant cytological features.

Adult↗