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Biomedical subjects

M Gapany

Publications and source records attributed to M Gapany.

At least 37 records · Page 2Linked to original sources
PubMed1995

Microcystic adnexal carcinoma: management options based on long-term follow-up.

Microcystic adnexal carcinoma (MAC), a recently described neoplasm that frequently affects the head and neck, presents a confusing problem for the clinician due to its unusual behavior. The individual cells have a bland microscopic appearance, and there is a predilection for neural invasion. Four cases of MAC are reported. All four cases demonstrate the difficulty with pathologic diagnosis. Follow-up of as long as 33 years begins to delineate the protracted nature of MAC. In addition, this paper includes the first report of a case of lymph node metastasis. Although resection may result in a significant defect, negative margins may not be achieved. Despite this, the defect can heal, as demonstrated by the cases described. In addition, MAC may recur many years later, irrespective of the status of the margins at the time of surgery. Given these unusual characteristics and the slowly progressive nature of MAC, strong consideration must be given to less radical surgical procedures, with close follow-up for grossly recurrent disease.

Aged↗
PubMed1995

Association of elevated protein kinase CK2 activity with aggressive behavior of squamous cell carcinoma of the head and neck.

BACKGROUND: Protein kinase CK2 (also known as casein kinase 2) is a messenger-independent protein serine/threonine kinase ubiquitously distributed in eukaryotes. CK2 has been found to phosphorylate a wide variety of cytosolic and nuclear substrates which are intimately involved in regulation of DNA, RNA, and protein synthesis, and differentiation. We therefore addressed the hypothesis that malignant transformation of upper aerodigestive tract mucosa to squamous cell carcinoma of the head and neck (SCCHN) might be associated with altered CK2 activity. MATERIALS AND METHODS: To this end, we subjected surgical specimens of SCCHN tumors and of normal oropharyngeal mucosa to subcellular fractionation. We then quantitated CK2 activity in cytosol and nuclei of these specimens using a CK2-specific peptide substrate (Arg-Arg-Arg-Glu-Glu-Glu-Thr-Glu-Glu-Glu). RESULTS: We found that CK2 activity was significantly elevated in both nuclear (p < 0.0005) and cytosolic (p < 0.0034) compartments of SCCHN tumors, relative to normal oropharyngeal mucosa. Moreover, CK2 activity in the cellular cytosolic fraction of SCCHN tumors was associated with less differentiated histologic grade (p < 0.037), positive nodal metastatic status (p < 0.056), and a poor clinical outcome (p < 0.028). Kaplan-Meier cumulative survival analysis revealed greatly reduced survival in the high-CK2 activity patient group, with high statistical significance (p < 0.023). CONCLUSIONS: These preliminary data reveal that malignant transformation of the upper aerodigestive tract mucosa is associated with altered CK2 activity. The results further suggest that dysregulation of this protein kinase may play a significant role in the pathobiology of SCCHN, and that CK2 activity may be a prognostic indicator in this malignancy.

Adult↗
PubMed1994

Immunohistochemical detection of c-myc protein in head and neck tumors.

OBJECTIVES: To evaluate the correlation between the levels of immunohistochemically detectable c-myc protein in squamous cell carcinoma of the head and neck and clinicopathologic prognostic variables utilized in clinical practice. DESIGN: Cohort study. SETTING: University and Veterans Administration medical centers, Cincinnati, Ohio. PATIENTS OR OTHER PARTICIPANTS: Consecutive samples. INTERVENTION: Surgery for squamous cell carcinoma of the head and neck. MAIN OUTCOME MEASURE: Correlation between c-myc expression and tumor size, nodal involvement, clinical disease stage, and degree of differentiation. Hypothesis formulated after data collection. RESULTS: Significant negative correlation between the c-myc levels and the number of metastatic nodes (P = .0001) and clinical stage of disease (P = .05). No correlation with tumor size or degree of differentiation. CONCLUSIONS: Reduction or loss of c-myc oncoprotein might be associated with metastatic lymph node involvement and advanced stages of squamous cell carcinoma of the head and neck. Further studies are needed to substantiate preliminary findings.

Adult↗
PubMed1993

Detection of P-glycoprotein in squamous cell carcinomas of the head and neck.

One established mechanism of multidrug resistance is elevated expression of P-glycoprotein. The expression of P-glycoprotein by immunohistochemistry was examined in squamous cell carcinomas of the head and neck using a newly developed monoclonal antibody, UIC2, which is specific to the human MDR1 gene product and recognizes an external epitope of the protein. P-glycoprotein was detected in 60% of the samples. MDR1 expression was compared with clinical response to chemotherapy in eight patients who received MDR1-dependent drugs and response was accurately predicted in seven (89%) of eight patients. Positive P-glycoprotein staining correlated with the degree of tumor differentiation, but not with other clinical factors. Therefore, analyzing the expression of P-glycoprotein may play a role when planning chemotherapeutic regimens for patients with head and neck cancer and may be an additional prognostic and diagnostic tool in these patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Relationship between immunohistochemically detectable p53 protein and prognostic factors in head and neck tumors.

This study examined the relationship between immunohistochemically detectable p53 protein and prognostic factors in squamous cell carcinoma of the head and neck (SCCHN). Twenty-seven tumor specimens were evaluated utilizing a panel of three monoclonal antibodies (MAbs) directed against different epitopes of the p53 protein (PAb 421, PAb 1801, and PAb 240). The overall incidence of p53 protein detection with a panel of MAbs was 78%, which was significantly higher than with any one of the tested antibodies. Comparison of the tumors that were negative for p53 with tumors that stained positive with one or multiple antibodies, however, revealed no statistically significant differences with respect to the stage of disease, metastatic node involvement, size of the primary tumor, or degree of tumor differentiation. The results of our study suggest that levels of p53 protein, although commonly immunohistochemically detected in head and neck tumors, do not correlate with known prognostic factors for SCCHN.

Adult↗
PubMed1992

[Free-flap reconstruction of the head and neck].

Free-flap microvascular surgery of the head and neck is now an accepted reconstructive technique. Optimal reconstruction of both function and form are achieved in selected patients by this method. We describe our experience with free-flap reconstruction of head and neck defects in 13 patients. In 5 oncologic patients reconstruction was immediate, while in 8 other oncologic and trauma patients it was delayed. The free rectus abdominis myocutaneous flap was used most often. 3 flaps required revision, but only 1 failed.

Adult↗
PubMed1992

c-myc, c-erbB-2, and Ki-67 expression in normal breast tissue and in invasive and noninvasive breast carcinoma.

c-myc, c-erbB-2, and Ki-67 expression was examined by immunohistochemistry in 11 normal breast tissues and 42 invasive and 14 noninvasive breast carcinomas. The c-myc product was detected in all breast carcinoma specimens and in 7 of 11 normal breast tissues. Invasive tumors stained more frequently with the anti-myc monoclonal antibody than did noninvasive tumors, while the level of expression in normal breast tissue was much less than that in breast cancer. Membrane staining of the c-erbB-2 protein was demonstrated in 29% (4 of 14) of noninvasive ductal carcinomas and in 45% (19 of 42) of invasive breast carcinomas. None of the 11 normal breast tissue samples was positive. The mean value of Ki-67-positive cells was 0.91 +/- 0.31% for normal breast tissue, 4.57 +/- 1.36% for noninvasive ductal carcinoma, and 12.76 +/- 2.18% for invasive breast cancer. In 42 invasive breast carcinomas, the expression of c-myc, c-erbB-2, and Ki-67 proliferation marker were compared with lymph node status, estrogen receptor status, progesterone receptor status, and age of patients at diagnosis. c-erbB-2 overexpression and Ki-67 overexpression were identified as the only factors associated with lymph node status. We concluded that they might be additional prognostic factors for breast carcinoma.

Breast↗
PubMed1992

Tumor necrosis factor and chemotherapeutic agents. Potentiation of cytotoxicity with interferon gamma.

This study examined combinations of the recombinant human cytokines, tumor necrosis factor alpha and interferon gamma, with doxorubicin and dactinomycin as well as other drugs on six squamous cell carcinoma cell lines of head and neck origin using the 3(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide proliferation assay. Interferon gamma significantly enhanced the cytotoxicity of tumor necrosis factor alpha with dactinomycin on all six cell lines investigated, while in four of six cell lines the cytotoxicity of tumor necrosis factor alpha with doxorubicin was significantly augmented by interferon gamma. Additional experiments showed no effect with either cytokine in combination with cisplatin, fluorouracil, methotrexate, or etoposide. These data demonstrate that human recombinant cytokines in concert with certain drugs improve in vitro cytotoxicity and may have a potential for improving in vivo therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

The effect of hyperbaric oxygen on growth of human squamous cell carcinoma xenografts.

Hyperbaric oxygen is an important adjunct to the treatment of patients with head and neck cancer with existing or recurrent wound healing problems. Anecdotal clinical observations and a recent study of chemically induced oral cancer in hamsters have raised concern that hyperbaric oxygen therapy may accelerate tumor growth in such patients. This study evaluated the effect of hyperbaric oxygen therapy on the growth of human squamous cell carcinoma xenografts in a proved animal model. Fresh tumor specimens from three patients with head and neck squamous cell carcinoma of varying degrees of differentiation were first subcutaneously transplanted into a nude mouse host. Growing xenografts were then transplanted into one of three mouse groups. Half of the mice in each group were given hyperbaric oxygen therapy. The transplant volume as an index of tumor growth was measured in controls and mice given hyperbaric oxygen therapy six times during the 3-week course. Xenograft growth was almost linear in all mice. No statistical difference in overall group mean growth rates was observed in mice given hyperbaric oxygen or control mice regardless of the degree of tumor differentiation. Xenograft tissue from all mice was microscopically examined for tumor mitotic indices and degree of differentiation. This study suggests that hyperbaric oxygen therapy has no effect on established tumor xenograft growth.

Animals↗
PubMed1990

Tumor necrosis factor and cytotoxic agents. Effect on squamous carcinoma lines.

The cytotoxicity of dactinomycin (actinomycin D), doxorubicin hydrochloride (Adriamycin), cisplatin, fluorouracil, and methotrexate alone and in combination with recombinant human tumor necrosis factor (rHuTNF) on human squamous cell carcinoma lines was studied by an MTT proliferation assay. The rHuTNF alone caused no inhibition after 24 to 72 hours. All lines investigated showed a dose-dependent response to dactinomycin and doxorubicin. Potentiation of dactinomycin and doxorubicin cytotoxicity occurred with four of six cell lines following incubation of rHuTNF and the drug. No synergistic effect on cytotoxicity was seen with rHuTNF and any chemotherapeutic agent on two cell lines. The addition of rHuTNF did not augment the cytotoxic effect seen with cisplatin, methotrexate, or fluorouracil on any cell line. These results show that rHuTNF can enhance the cytotoxic effect of certain chemotherapeutic agents on squamous cell lines in vitro.

Antineoplastic Agents↗
PubMed1985

Phenytoin bioavailability assessed by steady state serum concentrations.

The effect of a change in bioavailability of phenytoin sodium formulations on steady state serum concentrations was assessed in two groups of neurosurgical patients (n = 20 and 12). One group was studied in 1980 while on the old formulation, the other in 1983 while on the new formulation. Data were also obtained from routine therapeutic-level monitorings in 85 ambulatory patients receiving the new formulation during 1984. Phenytoin levels on the 400-mg/day dose were 10.9 +/- 4.1 (SD) and 16.1 +/- 5.6 micrograms/ml on the old and new formulations, respectively (P less than 0.01) in the neurosurgical patients. Routinely monitored levels on the 300-mg/day dose were 6.9 +/- 4.9 and 12.1 +/- 6.8 micrograms/ml, respectively (P less than 0.01). The maximum elimination rate of phenytoin, estimated from steady state dose-concentration pairs, was significantly higher on the old formulation (9.5 +/- 2.8 vs. 7.2 +/- 1.1 mg/kg per day, P less than 0.025) even though there was no difference in the estimates of the Michaelis-Menten constant. The proportion of subtherapeutic levels on ostensibly equal doses fell from 85 to 45% on 300 mg/day of the two formulations (P less than 0.01), and to 28% on 400 mg/day of the new formulation. Steady state concentrations may be used to assess increased bioavailability of drugs with capacity-limited metabolism, such as phenytoin.

Adult↗
PubMedDate not supplied

Evaluation of 201T1 SPECT for predicting early treatment response in patients with squamous cell carcinoma of the extracranial head and neck treated with nonsurgical organ preservation therapy: initial results.

PURPOSE: The purpose of this work was to prospectively determine the ability of 210TI single photon emission CT (SPECT) to monitor treatment response in patients with head and neck squamous cell carcinoma (HNSCCA) treated with nonsurgical organ preservation. METHOD: Nine patients with HNSCCA underwent 201T1 SPECT before and 6 weeks after completion of nonsurgical organ preservation therapy. All cases were evaluated for uptake at the primary site before and after treatment. All tumors had abnormal radiotracer uptake on the pretreatment study. The posttreatment thallium studies were evaluated for uptake and correlated with local control at the primary site in all cases. RESULTS: All patients had abnormal thallium uptake on pretreatment studies. Of the nine patients, four cases were locally controlled by nonsurgical organ preservation therapy. All of these patients had no evidence of thallium uptake on posttreatment studies. Five cases failed treatment at the primary site. All five patients demonstrated abnormal radiotracer uptake at the primary site. CONCLUSION: Our initial results suggest that 201T1 SPECT may be an accurate technique for monitoring HNSCCA treated with nonsurgical organ preservation therapy.

Carcinoma, Squamous Cell↗