Biomedical subjects

Bhuvanesh Singh

Publications and source records attributed to Bhuvanesh Singh.

At least 37 records · Page 2Linked to original sources

PubMed2005

Complications of craniofacial resection for malignant tumors of the skull base: report of an International Collaborative Study.

BACKGROUND: Advances in imaging, surgical technique, and perioperative care have made craniofacial resection (CFR) an effective and safe option for treating malignant tumors involving the skull base. The procedure does, however, have complications. Because of the relative rarity of these tumors, most existing data on postoperative complications come from individual reports of relatively small series of patients. This international collaborative report examines a large cohort of patients accumulated from multiple institutions with the aim of identifying patient-related and tumor-related predictors of postoperative morbidity and mortality and set a benchmark for future studies. METHODS: One thousand one hundred ninety-three patients from 17 institutions were analyzed for postoperative mortality and complications. Postoperative complications were classified into systemic, wound, central nervous system (CNS), and orbit. Statistical analyses were carried out in relation to patient characteristics, extent of disease, prior radiation treatment, and type of reconstruction to determine factors that predicted mortality or complications. RESULTS: Postoperative mortality occurred in 56 patients (4.7%). The presence of medical comorbidity was the only independent predictor of mortality. Postoperative complications occurred in 433 patients (36.3%). Wound complications occurred in 237 (19.8%), CNS-related complications in 193 (16.2%), orbital complications in 20 (1.7%), and systemic complications in 57 (4.8%) patients. Medical comorbidity, prior radiation therapy, and the extent of intracranial tumour involvement were independent predictors of postoperative complications. CONCLUSIONS: CFR is a safe surgical treatment for malignant tumors of the skull base, with an overall mortality of 4.7% and complication rate of 36.3%. The impact of medical comorbidity and intracranial tumor extent should be carefully considered when planning therapy for patients whose tumors are amenable to CFR.

Adolescent↗

PubMed2005

Second primary malignancy of the aerodigestive tract in patients treated for cancer of the oral cavity and larynx.

BACKGROUND: We aimed to identify patterns and predictors of second primary malignancy (SPM) of the aerodigestive tract (SPMADT) in patients with squamous cell carcinoma of the oral cavity (SCCOC) and larynx (SCCL). METHODS: One thousand two hundred fifty-seven patients from two existing databases were studied: 595 with SCCOC (1986-1995) and 662 with SCCL (1984-1998). The primary endpoint of interest was development of SPMADT, defined as a second primary neoplasm of the head and neck, esophagus, or lung. RESULTS: The 5-year SPMADT rate was 8% in the SCCL versus 10% in the SCCOC subgroup. Lung SPM was more common in the SCCL group; head and neck SPM was more common in the SCCOC group. Smokers had a fivefold increased risk, whereas alcohol use was associated with a twofold increased risk of SPMADT. CONCLUSIONS: The rates of SPMADT after treatment of SCCOC and SCCL are comparable, but the patterns are different. Smoking and alcohol use are independent predictors of SPMADT development.

Adolescent↗

PubMed2005

MUC1 plays a role in tumor maintenance in aggressive thyroid carcinomas.

BACKGROUND: We recently identified MUC1 as a target driving selection for 1q21 amplification and validated it as an independent marker of aggressive behavior in thyroid cancer (TC). The aims of this study were to determine whether TC cell lines retain MUC1 expression patterns that are seen in primary tumors, assess the role of MUC1 in tumor maintenance, and develop a virally delivered anti-MUC1 RNA interference (RNAi) that is effective in decreasing MUC1 expression in vitro. METHODS: Fifteen TC cell lines were screened for MUC1 protein expression. Cell lines with varying MUC1 protein levels were treated with anti-MUC1 monoclonal antibody to assess cell viability. A recombinant retroviral short hairpin RNAi delivery system against MUC1 was developed. Efficacy and optimal dosing of short hairpin RNA against MUC1 was determined. RESULTS: MUC1 expression patterns in TC cell lines were found to be similar to that seen in primary tumors. Treatment with anti-MUC1 antibody resulted in a significant decrease in cell viability in MUC1 over-expressing cell lines. MUC1-779 RNAi construct showed excellent infection efficiency and reproducible silencing. CONCLUSION: These data offer functional evidence that implicates MUC1 over-expression as a key molecular event in the pathogenesis of aggressive TC. Retrovirally delivered anti-MUC1 RNAi is effective in silencing MUC1 and merits further investigation to establish therapeutic efficacy and safety in anticipation of potential clinical application.

Antigens↗

PubMed2004

Treatment of aggressive thyroid cancer with an oncolytic herpes virus.

Although many thyroid cancers carry a favorable prognosis, there is a subgroup of patients with more aggressive histologies. Current therapies offer no significant survival benefit to patients with anaplastic thyroid carcinomas, which are considered fatal. Oncolytic herpes simplex viruses (HSVs) have potent antitumor effects against a variety of human malignancies. We assessed the activity of a replication-competent, attenuated, oncolytic HSV (NV1023) against 7 different thyroid cancers, including one papillary (NPA-187), one follicular (WRO82-1), one medullary (DRO81-1) and 4 anaplastic (DRO90-1, ARO, KAT-4C and KAT-18) cell lines. Only the follicular WRO82-1 line was resistant to NV1023 infection and cell lysis at a concentration of 5 viral pfu per cell (MOI 5). All other cell lines at MOI 5 demonstrated >95% infection in vitro at day 2 by X-gal staining and >88% cell death at day 4 by cytotoxicity assays. Even at MOI 0.1, 4 of these lines displayed complete cell death by day 7. Viral proliferation assays revealed that all of the nonfollicular cell lines supported logarithmic viral replication. Flank tumors of NPA-187, DRO81-1, DRO90-1 and ARO in athymic nude mice were treated with NV1023 (2 x 10(7) pfu). All NPA-187 tumors completely regressed following a single dose. DRO81-1 tumors demonstrated partial response with a single dose and significant improvement with 3 serial doses. ARO and DRO90-1 tumors showed a significant response following either single injection (54 +/- 22 and 292 +/- 138 mm3, respectively) or 3 serial injections (33 +/- 14 and 241 +/- 68 mm3, respectively) compared to saline injections (472 +/- 193 and 1,257 +/- 204 mm3, respectively) at day 20. These data suggest that herpes oncolytic therapy may be effective for the treatment of aggressive thyroid carcinomas and merits further investigation.

Adenocarcinoma, Follicular↗

PubMed2004

Identification of novel prognosticators of outcome in squamous cell carcinoma of the head and neck.

PURPOSE: The goal of this study was to identify chromosomal aberrations associated with poor outcome in patients with head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: We assessed the global genomic composition of 82 HNSCCs from previously untreated patients with comparative genomic hybridization (CGH). The CGH data were subcategorized into individual cytogenetic bands. Only genomic aberrations occurring in more than 5% of cases were analyzed, and redundancies were eliminated. Each aberration was submitted to univariate analysis to assess its relationship with disease-specific survival (DSS). We used Monte Carlo simulations (MCS) to adjust P values for the log-rank approximate chi(2) statistics for each abnormality and further applied the Hochberg-Benjamini procedure to adjust the P values for multiple testing of the large number of abnormalities. We then submitted abnormalities whose univariate tests resulted in an adjusted P value of less than.15 together with significant demographic/clinical variables to stepwise Cox proportional hazards regression. We again verified and adjusted P values for the chi(2) approximation of the final model by MCS. RESULTS: CGH analysis revealed a recurrent pattern of chromosomal aberrations typical for HNSCC. Univariate analysis revealed 38 abnormalities that were correlated with DSS. After controlling for multiple comparisons and confounding effects of stage, five chromosomal aberrations were significantly associated with outcome, including amplification at 11q13, gain of 12q24, and losses at 5q11, 6q14, and 21q11 (MCS adjusted P =.0009 to P =.01). CONCLUSION: HNSCC contains a complex pattern of chromosomal aberrations. A sequential approach to control for multiple comparisons and effect of confounding variables allows the identification of clinically relevant aberrations. The significance of each individual abnormality merits further consideration.

Aged↗

PubMed2004

Casein kinase II alpha subunit and C1-inhibitor are independent predictors of outcome in patients with squamous cell carcinoma of the lung.

PURPOSE: Gene expression profiling has been shown to be a valuable tool for prognostication and identification of cancer-associated genes in human malignancies. We aimed to identify potential prognostic marker(s) in non-small cell lung cancers using global gene expression profiles. EXPERIMENTAL DESIGN: Twenty-one previously untreated patients with non-small cell lung cancer were analyzed using the Affymetrix GeneChip high-density oligonucleotide array and comparative genomic hybridization. Identified candidate genes were validated in an independent cohort of 45 patients using quantitative real-time reverse transcription-PCR and Western blot analyses. Follow-up data for these patients was collected and used to assess outcome correlations. RESULTS: Hierarchical clustering analysis yielded three distinct subgroups based on gene expression profiling. Cluster I consisted of 4 patients with adenocarcinoma and 1 with squamous cell carcinoma (squamous cell carcinoma); clusters II and III consisted of 6 and 10 patients with squamous cell carcinoma, respectively. Outcome analysis was performed on the cluster groups containing solely squamous cell carcinoma, revealing significant differences in disease-specific survival rates. Moreover, patients having a combination of advanced Tumor-Node-Metastasis stage and assigned to the poor prognosis cluster group (cluster II) had significantly poorer outcomes. Comparative genomic hybridization analysis showed recurrent chromosomal losses at 1p, 3p, 17, 19, and 22 and gains/amplifications at 3q, 5p, and 8q, which did not vary significantly between the cluster groups. We internally and externally validated a subset of 11 cluster II (poor prognosis)-specific genes having corresponding chromosomal aberrations identified by comparative genomic hybridization as prognostic markers in an independent cohort of patients with lung squamous cell carcinoma identifying CSNK2A1 and C1-Inh as independent predictors of outcome. CONCLUSION: CSNK2A1 and C1-Inh are independent predictors of survival in lung squamous cell carcinoma patients and may be useful as prognostic markers.

Aged↗

PubMed2004

EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib.

Somatic mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene are reportedly associated with sensitivity of lung cancers to gefitinib (Iressa), kinase inhibitor. In-frame deletions occur in exon 19, whereas point mutations occur frequently in codon 858 (exon 21). We found from sequencing the EGFR TK domain that 7 of 10 gefitinib-sensitive tumors had similar types of alterations; no mutations were found in eight gefitinib-refractory tumors (P = 0.004). Five of seven tumors sensitive to erlotinib (Tarceva), a related kinase inhibitor for which the clinically relevant target is undocumented, had analogous somatic mutations, as opposed to none of 10 erlotinib-refractory tumors (P = 0.003). Because most mutation-positive tumors were adenocarcinomas from patients who smoked <100 cigarettes in a lifetime ("never smokers"), we screened EGFR exons 2-28 in 15 adenocarcinomas resected from untreated never smokers. Seven tumors had TK domain mutations, in contrast to 4 of 81 non-small cell lung cancers resected from untreated former or current smokers (P = 0.0001). Immunoblotting of lysates from cells transiently transfected with various EGFR constructs demonstrated that, compared to wild-type protein, an exon 19 deletion mutant induced diminished levels of phosphotyrosine, whereas the phosphorylation at tyrosine 1092 of an exon 21 point mutant was inhibited at 10-fold lower concentrations of drug. Collectively, these data show that adenocarcinomas from never smokers comprise a distinct subset of lung cancers, frequently containing mutations within the TK domain of EGFR that are associated with gefitinib and erlotinib sensitivity.

Adenocarcinoma↗

PubMed2004

Angiogenesis inhibition by an oncolytic herpes virus expressing interleukin 12.

PURPOSE: Oncolytic herpes simplex viruses (HSVs) may have significant antitumor effects resulting from the direct lysis of cancer cells. HSVs may also be used to express inserted transgenes to exploit additional therapeutic strategies. The ability of an interleukin (IL)-12-expressing HSV to treat squamous cell carcinoma (SCC) by inhibition of tumor angiogenesis is investigated in this study. EXPERIMENTAL DESIGN: A replication-competent, attenuated, oncolytic HSV carrying the murine IL-12 gene (NV1042), its non-cytokine-carrying analog (NV1023), or saline was used to treat established murine SCC flank tumors by intratumoral injection. The expression of secondary antiangiogenic mediators was measured. Angiogenesis inhibition was assessed by in vivo Matrigel plug assays, flank tumor subdermal vascularity, and in vitro endothelial cell tubule formation assay. RESULTS: Intratumoral injections of NV1042 (2 x 10(7) plaque-forming units) into murine SCC VII flank tumors resulted in smaller tumor volumes as compared with NV1023 or saline. IL-12 and IFN-gamma expression in tumors was 440 and 2.2 pg/mg, respectively, at 24 h after NV1042 injection, but both IL-12 and IFN-gamma were undetectable (<0.2 pg/mg) after NV1023 or saline injections. Expression of two antiangiogenesis mediators, monokine induced by IFN-gamma and IFN-inducible protein 10, was elevated after NV1042 treatment. Matrigel plug assays of NV1042-transfected SCC VII tumor cells demonstrated significantly decreased hemoglobin content and microvessel density as compared with NV1023 and PBS. Excised murine flank tumors treated with NV1042 had decreased subdermal vascularity as compared with NV1023 and PBS. Both splenocytes and IL-12 expression by NV1042 were required for in vitro inhibition of endothelial tubule formation. CONCLUSIONS: IL-12 expression by an oncolytic herpes virus enhances therapy of SCC through antiangiogenic mechanisms. Strategies combining HSV oncolysis with angiogenesis inhibition merit further investigation for potential clinical application.

Animals↗

PubMed2004

Activation of NF-kappaB and inhibition of p53-mediated apoptosis by API2/mucosa-associated lymphoid tissue 1 fusions promote oncogenesis.

Mucosa-associated lymphoid tissue (MALT) lymphoma is the most common extranodal lymphoid cell neoplasia; it frequently follows chronic bacteria-induced inflammation in various tissues. MALT lymphomas are characterized genetically by the t(11;18)(q21;q21) translocation, which yields chimeric transcripts encoding structurally distinct API2/MALT1 fusion proteins. In this study, we provide functional evidence for the contribution of API2/MALT1 fusion proteins to transformation of cells in culture by activating the NF-kappaB pathway through a RelB/p50 dimer. Using microchip gene expression analysis, we demonstrate that different forms of the API2/MALT1 proteins activate both unique and overlapping gene programs in cells. In addition to this genome reprogramming, expression of distinct API2/MALT1 fusion products inhibits DNA damage-induced, p53-mediated apoptosis in an NF-kappaB-dependent manner. Collectively, these data reveal previously unknown functional diversity among API2/MALT1 fusion products and their function in NF-kappaB signaling as it connects to the apoptotic program, a pathway with strong relevance to cancer. Furthermore, they provide evidence underlying the emerging role of the NF-kappaB signaling pathway in the inhibition of apoptosis.

Animals↗

PubMed2004

Genome-wide profiling of papillary thyroid cancer identifies MUC1 as an independent prognostic marker.

Clinicopathological variables used at present for prognostication and treatment selection for papillary thyroid carcinomas (PTCs) do not uniformly predict tumor behavior, necessitating identification of novel prognostic markers. Complicating the assessment is the long natural history of PTC and our rudimentary knowledge of its genetic composition. In this study we took advantage of differences in clinical behavior of two distinct variants of PTC, the aggressive tall-cell variant (TCV) and indolent conventional PTC (cPTC), to identify molecular prognosticators of outcome using complementary genome wide analyses. Comparative genome hybridization (CGH) and cDNA microarray (17,840 genes) analyses were used to detect changes in DNA copy number and gene expression in pathological cPTC and TCV. The findings from CGH and cDNA microarray analyses were correlated and validated by real-time PCR and immunohistochemical analyses on a series of 100 cases of cPTC and TCV. Genes identified by this approach were evaluated as prognostic markers in cPTC by immunohistochemistry on tissue arrays. CGH identified significant differences in the presence (76 versus 27%; P = 0.001) and type of DNA copy number aberrations in TCV compared with cPTC. Recurrent gains of 1p34-36, 1q21, 6p21-22, 9q34, 11q13, 17q25, 19, and 22 and losses of 2q21-31, 4, 5p14-q21, 6q11-22, 8q11-22, 9q11-32, and 13q21-31 were unique to TCV. Hierarchical clustering of gene expression profiles revealed significant overlap between TCV and cPTC, but further analysis identified 82 dysregulated genes differentially expressed among the PTC variants. Of these, MUC1 was of particular interest because amplification of 1q by CGH correlated with MUC1 amplification by real-time PCR analysis and protein overexpression by immunohistochemistry in TCV (P = 0.005). Multivariate analysis revealed a significant association between MUC1 overexpression and treatment outcome, independent of histopathological categorization (P = 0.03). Analysis of a validation series containing a matched group of aggressive and indolent cPTCs confirmed the association between MUC1 overexpression and survival (relative risk, 2.3; 95% confidence interval, 1.1-5.5; P = 0.03). Our data suggest that MUC1 dysregulation is associated with aggressive behavior of PTC and may serve as a prognostic marker and potential therapeutic target in this disease.

Carcinoma, Papillary↗

PubMed2004

Effective intravenous therapy of murine pulmonary metastases with an oncolytic herpes virus expressing interleukin 12.

PURPOSE: There currently is no therapy that enhances the survival of patients with distantly metastatic squamous cell carcinoma (SCC). Engineered herpes oncolytic viruses are effective therapeutic agents when delivered directly to tumors in animal models, but their efficacy in treating disseminated disease is poorly defined. EXPERIMENTAL DESIGN: We treated disseminated pulmonary SCC in mice with an interleukin (IL)-12-expressing oncolytic herpes virus (NV1042) or with the parent oncolytic virus (NV1023, IL-12 deficient) by i.v. tail vein administration. RESULTS: Lung IL-12 was 16.1 pg/mg and IFN-gamma was 4.3 pg/mg at day 1 after a single dose of NV1042 (5 x 10(7) plaque-forming units); levels of both were undetectable for NV1023. 5-Bromo-4-chloro-3-indolyl-beta-D-galactopyranoside histochemistry demonstrated viral infection of disseminated pulmonary tumor nodules by both vectors at day 1, with sparing of adjacent alveolar cells. NV1042-treated lungs showed no surface nodules at day 12, in contrast to NV1023-treated (92 +/- 27 surface nodules) and PBS-treated (225 +/- 9 surface nodules) lungs. Significantly enhanced survival was observed in NV1042-treated animals compared with NV1023- and PBS-treated animals (log rank < 0.05). In animals with a low tumor burden, 100% of NV1042-treated, 70% of NV1023-treated, and none of the control animals achieved long-term survival. NV1042 efficacy was similar to NV1023 efficacy in animals depleted of CD4/CD8 T lymphocytes, showing that IL-12 expression enhances oncolytic activity through immune effects. Histology showed no cytopathic effects in non-tumor-bearing lung, brain, spleen, liver, and pancreas after completion of viral therapy. No animals demonstrated any visible side effects attributable to viral therapy. CONCLUSIONS: The i.v. delivery of an oncolytic herpes virus may achieve effective infection, oncolysis, and transgene expression at distant tumor sites. This approach to systemic therapy combining oncolysis with IL-12 immune stimulation led to significantly improved survival in animals with disseminated SCC.

Animals↗

PubMed2004

Fine-needle aspiration biopsy of salivary gland lesions in a selected patient population.

OBJECTIVE: To report the role of selective use of preoperative fine-needle aspiration biopsy (FNAB) in patients with major salivary gland lesions at a tertiary care cancer center. DESIGN: Retrospective review of FNAB results compared with final histologic diagnosis as the criterion standard. SETTING: An academic tertiary care cancer center. PATIENTS: A consecutive series of 258 patients who underwent FNAB of major salivary gland lesions between 1996 and 2000, of whom 169 had surgical resection. MAIN OUTCOME MEASURES: Predictive value, sensitivity, specificity, and accuracy. RESULTS: FNAB was performed in 169 (37%) of 463 salivary gland lesions undergoing surgical procedures. A total of 126 lesions were in the parotid gland and 44 in the submandibular gland. Seventy-nine lesions (46%) were malignant. There were 150 FNAB specimens (89%) that were satisfactory for evaluation. The FNAB diagnosis of malignant or suspicious lesion had positive and negative predictive values of 84% and 77%, respectively. Ten of 20 false-negative FNAB results were low-grade lymphoma on final histologic assessment. Fine-needle aspiration biopsy diagnosis of a benign neoplasm had positive and negative predictive values of 83% and 88%, respectively. A cytopathologic diagnosis of a nonneoplastic lesion was predictive in only 47% of cases. Fifteen (47%) of 32 lymphocyte-predominant FNAB specimens were lymphoma on final histologic assessment. Ten (20%) of 49 patients with history of a solid, non-head and neck malignancy had evidence of distant metastasis to the salivary gland by histologic and/or cytopathologic assessment. CONCLUSIONS: An FNAB diagnosis of malignant or neoplastic major salivary gland disease is generally predictive of final histologic diagnosis. The predictive value of a negative FNAB finding is low, and should not supersede clinical suspicion. Cytologic findings of a lymphocyte-predominant lesion should prompt further workup to rule out lymphoma.

Adolescent↗

PubMed2004

Follicular variant of papillary thyroid carcinoma: genome-wide appraisal of a controversial entity.

The majority of thyroid tumors are classified as papillary (papillary thyroid carcinomas; PTCs) or follicular neoplasms (follicular thyroid adenomas and carcinomas; FTA/FTC) based on nuclear features and the cellular growth pattern. However, classification of the follicular variant of papillary thyroid carcinoma (FVPTC) remains an issue of debate. These tumors contain a predominantly follicular growth pattern but display nuclear features and overall clinical behavior consistent with PTC. In this study, we used comparative genomic hybridization (CGH) to compare the global chromosomal aberrations in FVPTC to the PTC of classical variant (classical PTC) and FTA/FTC. In addition, we assessed the presence of peroxisome proliferator-activated receptor-gamma (PPARG) alteration, a genetic event specific to FTA/FTC, using Southern blot and immunohistochemistry analyses. In sharp contrast to the findings in classical PTC (4% of cases), CGH analysis demonstrated that both FVPTC (59% of cases) and FTA/FTC (36% of cases) were commonly characterized by aneuploidy (P = 0.0002). Moreover, the pattern of chromosomal aberrations (gains at chromosome arms 2q, 4q, 5q, 6q, 8q, and 13q and deletions at 1p, 9q, 16q, 17q, 19q, and 22q) in the follicular variant of PTC closely resembled that of FTA/FTC. Aberrations in PPARG were uniquely detected in FVPTC and FTA/FTC. Our findings suggest a stronger relationship between the FVPTC and FTA/FTC than previously appreciated and support further consideration of the current classification of thyroid neoplasms.

Adult↗

PubMed2004

Genetic abnormalities associated with nodal metastasis in head and neck cancer.

BACKGROUND: Lymphatic metastasis represents the single most important clinical prognostic factor in head and neck squamous cell carcinoma (HNSCC), but underlying genetic mechanisms remain ill defined. Genetic differences between primary carcinomas and their corresponding metastases might form a key to understanding the metastatic phenotype. In this study we aimed to characterize such differences using a genome-wide screening measure. METHODS: Four human cell lines (MDA-686tu, MDA-686Ln, MDA-1386tu, MDA-1386Ln) derived from primary tumor and synchronous lymph node metastasis of two cases of metastatic HNSCC were subjected to comparative genomic hybridization (CGH) by differentially labeling DNA from tumor tissue and normal tissue with fluorescent agents. The labeled DNAs were simultaneously hybridized onto normal metaphase chromosomes. In addition, modified CGH was performed by directly hybridizing labeled primary tumor DNA against differentially labeled metastatic tumor DNA, allowing the direct detection of copy number differences in individual pairs. 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: In both cases, significant overlap was found between chromosomal aberrations present in the primary tumor and the corresponding nodal metastasis. However, several abnormalities differentiated primary tumors from their metastases. Modified CGH identified several genetic aberrations that were not detectable with the conventional CGH analysis. Gains at chromosomes 10p11-12 and 11p and deletions at chromosomes 4q22-31, 9p13-24, and 14q differentiated nodal metastases from the corresponding primary tumors in both cases. CONCLUSIONS: The combination of conventional and modified CGH analyses facilitates the identification of DNA copy number changes that might be involved in the development of a metastatic phenotype. Future research should aim at the identification of the genes involved at the identified sites of chromosomal aberration.

Aged↗

PubMed2004

Cancer of the oral cavity: a comparison between institutions in a developing and a developed nation.

BACKGROUND: The literature suggests that the natural history of squamous cell carcinoma of the oral cavity may vary and the prognosis is different in patients from developing and developed nations. The objective of this study was to compare the clinical presentation, management, and outcome of patients with oral cancer treated at tertiary care cancer institutions in a developing nation (Brazil- Centro de Tratamento e Pesquisa Hospital do Cancer A. C. Camargo [HCACC]) with those from a developed nation (United States- Memorial Sloan-Kettering Cancer Center [MSKCC]). METHODS: Between January 1990 and December 1994, 602 patients underwent initial treatment in the study institutions. RESULTS: Overall, patients from HCACC had a higher predominance of men (78.8% vs 54.6%; p <.001) and a higher prevalence of tobacco (88.1% vs 77.8%; p =.002) and alcohol consumption (80.9% vs 69.8%; p =.004). More patients at HCACC had advanced disease (stage III/IV; 73.4% vs 37.4%; p<.001). Even though the overall outcome was poorer in patients from HCACC (p <.001), after controlling for stage, there was not a statistically significant difference in disease-free or overall survival between the two institutions. Only at cancer-specific survival for early-stage disease (stage I/II) patients showed a difference (p =.05). Moreover, clinical stage (RR, 3.7; 95% CI, 2.6-5.5) and definitive treatment (RR, 3.3; 95% CI, 2.4-4.6) were the only factors that remained as significant predictors of outcome on multivariate analysis. Finally, the rate of subsequent second primary cancers was higher in patients from HCACC (p =.03). CONCLUSIONS: Statistically significant differences were found in clinical presentation, tumor characteristics, and outcome in OC patients between the two institutions from a developing and developed nation. Overall outcome was poorer in HACC patients. However, after controlling for site, stage, and treatment, the outcome of these patients was similar, with the exception of a higher rate of occurrence of second primary cancers in patients from HACC. Given that the use of standard protocols of treatment offer similar outcomes, the establishment of education programs and screening measures for early diagnosis might be the best chance to improve overall outcome in OC patients in developing nations.

Alcohol Drinking↗

PubMed2004

SCCRO expression correlates with invasive progression in bronchioloalveolar carcinoma.

BACKGROUND: Overexpression of squamous cell carcinoma-related oncogene (SCCRO) is associated with invasive progression and poor outcomes in non-small cell lung cancer. We assessed the role of SCCRO as a tumor marker in bronchioloalveolar carcinoma (BAC), a subtype of adenocarcinoma exhibiting evidence of histologic tumor progression. We hypothesized that SCCRO expression would correlate with invasive tumor phenotypes and worse survival in BAC. METHODS: We classified 150 tumors as pure BAC, BAC with focal invasion, or adenocarcinoma with BAC features. A tissue microarray was constructed from areas of benign lung, BAC, and invasive adenocarcinoma in these tumors. Squamous cell carcinoma-related oncogene expression was graded by immunohistochemistry from 0 to 3 (absent, low, moderate, or high), with positive SCCRO phenotype defined as grade 3. Squamous cell carcinoma-related oncogene specificity was determined by Wilcoxon rank test and area under the receiver-operator curve, survival by the Kaplan-Meier method, and correlation with prognostic factors by log-rank test. RESULTS: Of the 86.0% (129 of 150) of specimens suitable for analysis, positive SCCRO phenotype was seen in 16.3% (21 of 129) and was 100.0% specific for tumor versus benign tissue (area under receiver-operator curve, 0.92). Positive SCCRO phenotype was greater in tumors with increasing degrees of invasive histologic type (7.0% pure BAC, 13.6% BAC with focal invasion, and 28.6% adenocarcinoma with BAC features; p = 0.02). Low-level SCCRO expression was present in 83.9% (99 of 118) of benign tissues and correlated with tobacco use and poor survival (p = 0.05). CONCLUSIONS: Squamous cell carcinoma-related oncogene is a marker of invasive tumor progression in BAC. Low-level expression in adjacent benign lung predicts worse survival, and may represent field cancerization or host-tumor effects.

Adenocarcinoma↗

PubMed2004

Squamous cell carcinoma-related oncogene is highly expressed in developing, normal, and adenomatous adrenal tissue but not in aggressive adrenocortical carcinomas.

BACKGROUND: Our previous work has demonstrated squamous cell carcinoma-related oncogene (SCCRO) expression in adult murine adrenocortical tissue. The aim of this study was to assess patterns of SCCRO expression in the embryonic murine adrenal gland, and in normal and neoplastic human adrenocortical tissues in order to determine its role as a marker of differentiation in adrenocortical development and neoplastic progression. METHODS: Murine embryos were procured at developmental stages E8 to E18. A tissue microarray was constructed containing 38 normal, 39 adenomatous, and 87 carcinomatous human adrenocortical specimens. Immunohistochemistry for SCCRO was performed and its expression was graded in suitable tissues. RESULTS: SCCRO expression was detected in the murine adrenal cortex as early as E15 and persisted into the postnatal period. High-level SCCRO expression was identified in 94% of normal (32/34) and adenomatous (29/31) adrenocortical specimens but in only 63% (45/72) of adrenocortical carcinoma (ACC) specimens ( P = .001). Loss of SCCRO expression in primary ACC (13/34 (34%)) correlated with advanced stage ( P = .06), presence of M1 disease at presentation ( P = .03), and worse overall survival ( P = .006). CONCLUSIONS: SCCRO appears to be a marker of adrenocortical differentiation in both murine and human systems. SCCRO expression may be useful in distinguishing adrenocortical adenomas from ACC. Moreover, loss of SCCRO expression in primary ACC is associated with worse outcome and may be a marker of progressive dedifferentiation in these tumors.

Adrenal Cortex Neoplasms↗

PubMed2004

Interest in and barriers to participation in multiple family groups among head and neck cancer survivors and their primary family caregivers.

This study examined interest in and barriers to participation in a multiple family group intervention (MFG) for adult cancer survivors and their family caregivers. The intervention was developed to assist families in coping with the persistent challenges of cancer diagnosis, treatment, and rehabilitation. Eighty eligible families having a member diagnosed and treated for cancers of the head and neck region completed a baseline quality of life survey consisting of standardized psychosocial measures, and then all patients and their families were invited to participate in a day-long multiple family group program. However, despite extensive recruitment efforts and accommodations to address anticipated barriers for nonparticipation, only 15 of the 80 (19%) eligible families agreed to attend the MFG workshop. Post-MFG, participating families reported high levels of program satisfaction and usefulness. These findings are discussed in the context of increasing the use of family-focused interventions in cancer care settings.

Adaptation, Psychological↗