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Biomedical subjects

J F Ensley

Publications and source records attributed to J F Ensley.

At least 37 records · Page 2Linked to original sources
PubMed1996

The clinical application of DNA content and kinetic parameters in the treatment of patients with squamous cell carcinomas of the head and neck.

Patients with squamous cell cancers of the head and neck (SCCHN) vary tremendously in their natural history and treatment outcome even amongst subgroups where the clinical and morphological parameters are similar. The ability to pretherapeutically identify individual patients and patient subgroups that differ in these regards would greatly facilitate clinical and basic science cancer research in this tumor. DNA content parameters are simple and accurate intermediate markers of a tumor's biology and reflect the fundamental process associated with the development of malignancy, chromosomal aneuploidy. In patients with SCCHN, DNA content parameters have been shown to be highly predictive of the natural history of the tumor and treatment outcome. They are also useful as intermediate markers for the study of the underlying molecular-genetic properties and processes responsible for the biological differences seen in these cancers. DNA content parameters therefore serve as fundamental 'translational' bridges in clinical and laboratory research in patients with SCCHN.

Carcinoma, Squamous Cell↗
PubMed1996

Evaluation of topotecan in patients with recurrent for metastatic squamous cell carcinoma of the head and neck. A phase II Southwest Oncology Group study.

Twenty-nine patients with persistent, recurrent and/or metastatic squamous cell carcinoma of the head and neck were treated daily for five days at three-week intervals with topotecan 1.5 mg/m2. Four patients received prior chemotherapy, 23 prior surgery and 29 prior radiation therapy. Of the 29 eligible patients, 8 patients were not evaluable for response and were assumed to be non-responders. Of the remaining 21 evaluable patients, there were zero responses (0%, 95% confidence interval [0,.12]). The most common toxicities were myelosuppression, dyspnea and malaise/fatigue/lethargy. Topotecan has limited activity in advanced head and neck cancer with this dose and schedule.

Adult↗
PubMed1995

Tyrosine phosphorylation as a marker for aberrantly regulated growth-promoting pathways in cell lines derived from head and neck malignancies.

We have utilized a broad approach to address whether tyrosine kinases and the growth pathways they regulate might be functionally aberrant in squamous cell carcinomas (SCC) of the upper aerodigestive tract. This strategy involved assaying for evidence of tyrosine kinase action in lysates of cell lines representing SCC. Our findings revealed a spectrum of elevated tyrosine phosphorylation in SCC lines ranging from less than 2-fold to more than 10-fold above that of control human epidermal keratinocytes. Thus the ability to regulate growth and other pathways controlled by tyrosine phosphorylation was impaired in all the 19 lines examined. Assessment of the receptor for epidermal growth factor (EGF) revealed that its activity was elevated above normal in 14 of the 19 cell lines examined, suggesting that at least a portion of the increased tyrosine phosphorylation observed could be attributed to excessive EGF receptor activity. Our findings provide functional evidence that growth pathways are aberrantly regulated in cell lines representing SCC of the upper aerodigestive tract.

Biomarkers, Tumor↗
PubMed1994

MTS1/CDK4I is altered in cell lines derived from primary and metastatic oral squamous cell carcinoma.

The MTS1/CDK4I gene encodes a 16 kDa cyclin kinase inhibitor and maps to chromosome 9p21. Previous studies have suggested the presence of a major tumour suppressor gene at this locus which may be inactivated in head and neck squamous cell carcinoma (HNSCC). To determine the status of this gene in human primary and metastatic HNSCC, we examined the locus and its transcript for abnormalities by polymerase chain reaction (PCR). Out of 14 cell lines studied, four had lost only exon 1, one had lost only exon 2, three had lost both exons 1 and 2, and none of the remaining six lines expressed a normal p16 mRNA. These latter six cell lines expressed p16 transcripts that had suffered deletions ranging in size from 2-16 base pairs. In each case, deletions led to a change of reading frame. Furthermore, in two cases abnormalities in the MTS1/CDK4I gene were identical in cells derived from metastatic tumours as compared to cells derived independently from the corresponding primary tumour. The identical nature of mutations observed in primary tumours and metastases derived from the same patient provides strong evidence that inactivation of p16 function was an in vivo event.

Base Sequence↗
PubMed1993

Flow cytometric DNA analysis of fresh prostatic resections. Correlation with conventional prognostic parameters in patients with prostate cancer.

BACKGROUND: DNA ploidy analysis has been investigated as a prognostic indicator in prostate cancer. Most of the data is derived from retrospective studies using paraffin-embedded tissue. This method has drawbacks related to the quality of DNA histograms and uncontrolled data collection. METHODS: DNA ploidy analysis of freshly resected prostatic tissue was prospectively compared with conventional prognostic variables in 97 men treated with radical prostatectomy for localized prostate cancer. RESULTS: Regarding the patients, 31.9% were African American and 66% had pathologic Stages C or D1 disease. Only 9.6% of patients with Stages A2 and B had a prostate-specific antigen (PSA) value greater than 10 ng/ml, whereas 97% of patients with PSA values greater than 20 ng/ml had pathologic Stages C and D1. PSA levels correlated with Gleason score (P = < 0.05); 51% and 100% of patients with Gleason score 5-7 and 8-10, respectively, had PSA values greater than 10 ng/ml. Twenty-two patients (23%) had DNA aneuploid tumors. Comparisons of mechanical to enzymatic cell suspensions indicated that DNA aneuploidy was better preserved in mechanical cell preparations. DNA ploidy correlated with pathologic stage (P = < 0.05) and Gleason score (P = < 0.05). Fifteen of 79 patients (18.9%) with Gleason score 5-7 had DNA aneuploid tumors versus 71.4% of patients with Gleason score 8-10. PSA groups correlated with ploidy status (P = 0.01). Although the majority of patients (19 of 22) with DNA aneuploid tumors had elevated preoperative PSA levels, none had a PSA value greater than 50 ng/ml. CONCLUSIONS: DNA ploidy analysis correlated with established prognostic indicators in prostate cancer; however, its independent correlation with natural history and treatment outcome must be established for it to have an effect on therapeutic decisions.

Aged↗
PubMed1993

DNA content parameters of paraffin-embedded soft tissue sarcomas: optimization of retrieval technique and comparison to fresh tissue.

DNA content analysis of formalin fixed paraffin embedded (FFPE) tissue permits determination of the influence of DNA content on the prognosis in cohorts of patients for whom the clinical outcome is known. Of key importance in such an analysis is the accuracy of DNA content determination. Variations in the quality of DNA histograms from FFPE tissues of different types prompted a comparative evaluation of the preparative methodology of FFPE soft tissue sarcomas for DNA flow cytometry. Following deparaffination and rehydration of fixed tissue, and prior to fluorochrome staining, tissue blocks of 15 DNA aneuploid soft tissue sarcomas were subjected to repeated experimental (time x concentration) enzyme exposures. The goal of these studies was to define the optimal tissue specific retrieval technique with the coefficient of variation, maintenance of DNA aneuploidy, and DNA index as endpoints. After optimizing the technique, the DNA content of 50 soft tissue neoplasms derived from FFPE specimens was compared to the corresponding fresh surgical tissue. The observed 14 percent error rate in the determination of DNA ploidy status suggest limited utility for FFPE tissue in prospective therapeutic trials of soft tissue sarcoma.

Cell Count↗
PubMed1993

Variations in DNA aneuploid cell content during tumor dissociation in human colon and head and neck cancers analyzed by flow cytometry.

Experimental research involving human solid tumors often requires single cell suspensions of high yield that are representative of the tissue of origin and in which the cellular property of interest is preserved. This is particularly necessary for the determination of DNA ploidy by flow cytometry. Mechanical dissaggregation and proteolytic enzyme digestion are the most commonly employed dissociation techniques for solid tumors. Comparative testing of techniques is often not performed. Mechanical and proteolytic enzyme dissociation techniques were comparatively tested in 77 human squamous cell cancers of the head and neck (SCCHN) and 25 human colon cancers for cellular yield, dye exclusion viability, quality, and morphology of DNA histograms, and the presence and proportion of DNA aneuploid subpopulations. Significant and consistent DNA aneuploid subpopulation losses were noted in mechanical preparations of SCCHN and enzymatic preparations of colon cancers. The frequency of SCCHN specimens with DNA aneuploid subpopulations was underestimated by 52% in mechanical cell suspensions, and the proportion of DNA aneuploid cells was diminished in an additional 30% of the specimens. Conversely, the frequency of specimens with DNA aneuploid subpopulations was underestimated by 38% in cell suspensions from enzymatically dissociated human colon cancer and their proportion diminished in an additional 50% of the specimens. Incubations of human colon cancers with three commonly employed proteolytic enzymes demonstrated a progressive loss of DNA aneuploid subpopulations as a function of enzyme concentration and incubation time. This is a serious potential source of error in the flow cytometric determination of DNA ploidy in human solid tumors, and may contribute to the diversity of results obtained and occasional contradictory conclusions reached in such studies.

Adult↗
PubMed1993

Development and optimization of tissue preparative methodology for DNA content analysis of soft tissue neoplasms.

Data regarding DNA content parameters in soft tissue sarcoma is limited. Development and optimization of tissue specific preparative techniques for DNA flow cytometry was undertaken prior to routine DNA content analysis of soft tissue neoplasms; 154 soft tissue tumors were studied. Dissociation dependent differences in cellular yields, viabilities, maintenance of DNA aneuploid populations, coefficients of variation, and DNA index supported the need for these developmental studies. Fifty-six of eighty-nine patients had DNA aneuploid soft tissue sarcomas. A relationship between DNA aneuploidy and grade was seen in this series with 38% with low grade, 59% with moderate grade, and 69% with high grade tumors demonstrating DNA aneuploid populations (P < 0.005). The mean S-phase fraction for DNA diploid and aneuploid sarcomas was 7.2% and 13.3%, respectively (P < 0.001). When classified by histologic grade of the primary tumor, a greater percentage of metastatic lesions were DNA aneuploid (4 of 7 grade 2 lesions, and 15 of 16 grade 3 lesions). Decreases in cellular yields and rate of DNA aneuploidy were observed in a subgroup of patients with localized high grade sarcoma treated preoperatively, as compared to patients treated with initial surgery. Prospective correlation of DNA content parameters to prognosis and response to cytotoxic therapy are now possible and are ongoing.

Aneuploidy↗
PubMed1992

DNA ploidy of primary and metastatic squamous cell head and neck cancers.

Regional metastases are a major determinant in the treatment outcome of patients with squamous cell carcinoma of the head and neck. Metastases do not respond as well to cytotoxic therapy as do primary tumors. DNA diploid tumors or tumor components also respond poorly to intermittent cytotoxic therapy. In our series of 497 patients with squamous cell carcinoma of the head and neck, the percentage of pure DNA diploid tumors and the mean DNA indexes in 497 primary tumors and 82 regional metastases were 34% and 1.54 and 50% and 1.34, respectively. Paired comparisons were performed in 61 patients and revealed a statistically significant increase in the frequency of DNA diploid tumors (27.4% to 41.2%) in associated lymph node metastases. The clinical observation that patients with squamous cell carcinoma of the head and neck and regional lymph node metastases have a poorer prognosis and a poorer response to cytotoxic therapy may in part be explained by the increased incidence of DNA diploid tumors in their regional lymph nodes, and the poorer response of such tumors to cytotoxic therapy.

Carcinoma, Squamous Cell↗
PubMed1992

Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: a Southwest Oncology Group study.

PURPOSE: The Southwest Oncology Group (SWOG) conducted a randomized comparison of cisplatin plus fluorouracil (5-FU) and carboplatin plus 5-FU versus single-agent methotrexate (MTX) in patients with recurrent and metastatic squamous-cell carcinoma (SCC) of the head and neck. The primary objective was to compare separately the response rates of each combination regimen to standard weekly MTX. PATIENTS AND METHODS: Two hundred seventy-seven patients diagnosed with SCC of the head and neck were randomized to one of three treatments: (1) cisplatin 100 mg/m2 intravenously (IV) on day 1 and 5-FU 1,000 mg/m2 per day for a 96-hour continuous infusion repeated every 21 days; (2) carboplatin 300 mg/m2 IV on day 1 and 5-FU 1,000 mg/m2 per day for a 96-hour continuous infusion repeated every 28 days; and (3) MTX 40 mg/m2 IV given weekly. RESULTS: All three treatment regimens were well tolerated. However, both hematologic and nonhematologic toxicities were significantly greater with cisplatin plus 5-FU compared with MTX (P = .001). Toxicity from carboplatin plus 5-FU was intermediate compared with the other regimens. The complete and partial response rates were 32% for cisplatin plus 5-FU, 21% for carboplatin plus 5-FU, and 10% for MTX. The comparison of cisplatin plus 5-FU to MTX was statistically significant (P less than .001), and the comparison of carboplatin plus 5-FU to MTX was of borderline statistical significance (P = .05). Median response durations and median survival times were similar for all three treatment groups. Logistic regression models showed that only treatment assigned was associated significantly with response (P = .001). Cox proportional hazards models indicated that only performance status was associated significantly with survival (P less than .01). CONCLUSIONS: We conclude that combination chemotherapy resulted in improved response rates but was associated with an increased toxicity and no improvement in overall survival. Therefore, new treatments that may alter the course of disease in recurrent head and neck cancer patients still need to be identified.

Adult↗
PubMed1991

The role of infection in the morbidity and mortality of patients with head and neck cancer undergoing multimodality therapy.

Cancer of the head and neck is a common cancer worldwide. The majority of patients present with locally advanced disease. Recently a great deal of improvement has been made in multimodality therapy of this disease, warranting more careful consideration of factors affecting quality of life, disease course, and treatment. Infection is clearly a factor. Analysis of 662 hospital admissions of 169 head and neck cancer patients was performed. A definite infection was documented in 86 febrile episodes, pneumonia contributed to 40%, bacteremia to 13%, skin and soft tissue infection to 12%, and tracheobronchitis to 10%. Among the evaluated risk factors, foreign bodies, specifically intravenous (IV) cannulae and gastrostomy tubes, race, performance status, alcohol intake, and nutritional status were statistically significant variables that predicted for or were associated with infection. Infection contributed to 44% of the deaths.

Adult↗
PubMed1991

The Wayne State University experience with adjuvant chemotherapy of head and neck cancer.

Because of the poor results of standard therapy in patients with locally advanced head and neck cancers, chemotherapy is increasingly used to improve the outcome of these patients. In resectable disease, chemotherapy is being investigated before definitive treatments, after surgery, concurrent with postoperative radiotherapy, after radiotherapy, and for possible laryngeal salvage. In unresectable cancers, chemotherapy before, concurrent with, and following radiotherapy is being investigated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

A common cytogenetic abnormality and DNA content alterations in dedifferentiated chondrosarcoma.

Dedifferentiated chondrosarcoma is an uncommon and aggressive variant of chondrosarcoma. The authors report the flow cytometric characteristics and cytogenetic findings in culture of two cases of dedifferentiated chondrosarcoma. The first case was DNA diploid by flow cytometry but had cytogenetic abnormalities consisting of breaks in the short arms of both chromosomes 1, resulting in deletion in one homolog and recombination in the other. In addition, cells from this tumor showed a balanced translocation between chromosomes 4 and 5, deletion of chromosome 9, and monosomy for chromosome 10. The second case was DNA aneuploid and more complex cytogenetically but had, in common with the first case, rearrangement and translocation at the same band on chromosome 1. These cytogenetic changes are compared with abnormalities previously reported for chondrosarcoma. Possible relationships between the nonrandom chromosomal abnormalities and subclassification among chondrosarcomas are discussed.

Aged↗
PubMed1989

Metastatic squamous cell carcinoma of an unknown primary localized to the neck. Advantages of an aggressive treatment.

Treatment of patients with squamous cell carcinoma (SCC) of an unknown primary localized to the neck is still controversial, particularly regarding advanced disease. We reviewed 41 such patients treated with surgery and/or radiotherapy (RT) (n = 25) or with combined modality treatment including chemotherapy (CH) (n = 16). The male to female ratio was 28 to 13, and the median age was 58 years (range, 32 to 94 years). There were 27 (66%) patients with poorly differentiated SCC and 8 with moderately differentiated or well-differentiated cancer. Twenty-three (56%) patients had N3 disease, 16 (39%) had N2, and 2 had N1. The majority of N3 patients have been treated with CH and RT (n = 12) or with RT alone (n = 9). The combined CH-RT was well tolerated, with no life-threatening toxicity. The complete response (CR) to CH-RT was 81% (11 patients have no evidence of disease [NED] currently). The median survival time of this group was 37+ months. Of the 25 patients who had surgery and/or RT as their first planned treatment, 7 (28%) have NED currently. The median survival time of this group was 24 months. Patients with N3 disease who received CH had a higher CR rate and a longer survival time as compared with those treated with surgery and/or RT, despite a higher (N3) stage of disease. These findings warrant further investigation in randomized cooperative studies.

Adult↗