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Biomedical subjects

K K Fu

Publications and source records attributed to K K Fu.

At least 37 records · Page 2Linked to original sources

Benzo[a]pyrene diol epoxide and bleomycin sensitivity and susceptibility to cancer of upper aerodigestive tract.

BACKGROUND: Tobacco smoking is an established risk factor for cancers of the upper aerodigestive tract, and measurement of chromosomal aberrations, i.e., chromatid breaks, induced in lymphocytes in vitro by bleomycin has been shown to be a predictor of risk for these cancers. In a case-control study, we recruited case subjects who were previously treated with surgery and/or radiotherapy for stage I or stage II squamous cell carcinoma of the head and neck to test the hypothesis that lymphocytic chromatid breaks induced by benzo[a]pyrene diol epoxide (BPDE), a tobacco mutagen, may also be associated with risk of developing cancers of the upper aerodigestive tract. METHODS: Case subjects were matched to control subjects on the basis of age, sex, ethnicity, and smoking status. Primary lymphocytes from 67 case subjects and 81 control subjects were treated with 2 microM BPDE for 24 hours, and the frequency of induced chromatid breaks was determined. All statistical tests were two-sided. RESULTS: Lymphocytes from case subjects compared with lymphocytes from control subjects showed significantly more breaks per cell induced by BPDE (mean+/-standard deviation, 0.77+/-0.38 versus 0.49+/-0.25; P<.001). Lymphocytes from 64.2% of case subjects were sensitive to BPDE (using a cutoff value of > or =0.60 break per cell). Subjects in the highest quartile of chromatid breaks had an approximately 20-fold increased risk of cancer compared with those in the lowest quartile after adjustment for age, sex, ethnicity, and smoking status. The association between BPDE sensitivity and cancer risk was higher in former smokers than in current smokers and higher in younger patients than in older patients. Subjects with sensitivity to both BPDE and bleomycin were at a 19.2-fold increased risk of cancer compared with those who were not sensitive to either agent. CONCLUSIONS: Mutagen sensitivity assays may aid in identifying individuals at risk of cancer, and use of parallel assays with two mutagens may improve risk predictability.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

Results and prognostic factors in the retreatment of locally recurrent nasopharyngeal carcinoma.

PURPOSE: To review the results and evaluate the prognostic factors in the retreatment of locally recurrent nasopharyngeal carcinoma. METHODS AND MATERIALS: We reviewed the records of 74 patients with locally recurrent nasopharyngeal carcinoma treated at the University of California, San Francisco between 1957 and 1995. The histologic types included squamous cell carcinoma in 6 (8.1%), nonkeratinizing carcinoma in 48 (64.9%), and undifferentiated carcinoma in 20 (27%) cases. The site of recurrence was in the primary in 46 (62.2%), in the neck nodes in 20 (27%), and in both sites in 8 (10.8%) patients. The recurrent disease was Stage I in 10 (13.5%), Stage II in 16 (21.6%), Stage III in 20 (27%), and Stage IV in 28 (37.9%) patients. Thirty-seven (50%) patients developed recurrence within 2 years and 58 (78.4%) within 5 years after initial treatment. Radiotherapeutic techniques used in the retreatment of primary recurrence consisted of external beam radiotherapy (EBRT), intracavitary brachytherapy, heavy-charged particle beam, and gamma knife, alone or in combination. Reirradiation doses ranged from 18 to 108 Gy, with a median dose of 60 Gy. Treatment of recurrent neck nodes consisted of radical neck dissection (RND) +/- intraoperative radiotherapy (IORT), or EBRT +/- hyperthermia, or chemotherapy +/- hyperthermia. Chemotherapy was used in 22 (30%) patients. Median follow-up was 20 months (range: 2 to 308 months). RESULTS: The 3-, 5-, and 10-year actuarial overall survival following retreatment were 49, 37, 18%, respectively. Thirty-six patients (49%) were free of further local-regional recurrence after retreatment. The 3-, 5-, and 10-year local-regional progression-free rates were 52, 40, and 38%, respectively. On univariate analysis, histologic type (p < 0.0001), interval to recurrence (p = 0.034), and treatment modality for early-stage disease (p = 0.01) were significant prognostic factors for overall survival, with age being marginally significant (p = 0.053). For local-regional progression-free rate, only histology was significant (p = 0.035). On multivariate analysis, age (p = 0.026), histology (p = 0.015), and interval to recurrence (p = 0.030) were significant for overall survival, and only histology (p = 0.002) and presence of complications (p = 0.016) were significant for local-regional progression-free rate. Of the 64 reirradiated patients, late complications were documented in 29 (45%) patients. The late complications were permanent in 21 (33%) and severe in 15 (23%) patients. CONCLUSION: Retreatment using radiotherapy alone or in combination with other treatment modalities can achieve long-term local-regional control and survival in a substantial proportion of patients with locally recurrent nasopharyngeal carcinoma. Age, histology, and interval to recurrence were independent prognostic factors for overall survival, but only histology and presence of complications were significant for local-regional progression-free rate.

Adult↗

Precisely defining high-risk operable head and neck tumors based on RTOG #85-03 and #88-24: targets for postoperative radiochemotherapy?

BACKGROUND: Local-regional recurrence of disease remains the major obstacle to cure of advanced head and neck cancers. METHODS: This investigation reviewed data derived from Radiation Therapy Oncology Group (RTOG) protocols #85-03 and #88-24 to identify characteristics of tumors that predicted local-regional recurrence of disease following surgery and postoperative radiotherapy (RT). RESULTS: The presence of tumor in two or more lymph nodes, and/or extracapsular spread of nodal disease, and/or microscopic-size tumor involvement of the surgical margins of resection imparts a high risk of local-regional (L-R) relapse. Our data also support the hypothesis that, following surgery, the concurrent addition of chemotherapy (CT) to RT may increase the likelihood of L-R control of disease for patients who have these high-risk characteristics. CONCLUSION: A prospective trial of surgery followed by concurrent RT and CT is warranted for patients who have high-risk characteristics found at surgery.

Carcinoma, Squamous Cell↗

Combined radiotherapy and chemotherapy for nasopharyngeal carcinoma.

Among squamous cell carcinomas of the head and neck, nasopharyngeal carcinoma is probably the most radiosensitive and chemosensitive. It also has the highest incidence of distant metastasis. This article reviews the results of randomized trials of combined chemotherapy and radiotherapy for nasopharyngeal carcinoma to date. Induction chemotherapy with bleomycin, epirubicin, and cisplatin was shown to increase disease-free survival but not overall survival in a trial by the International Nasopharyngeal Cancer Study Group. Concurrent radiotherapy and cisplatin followed by adjuvant cisplatin and 5-fluorouracil infusion significantly decreased local, nodal, and distant failures and increased progression-free and overall survival in the Head and Neck Intergroup Trial. The toxicity of combined chemotherapy and radiotherapy, however, primarily acute toxicity, was significantly greater than that of radiotherapy alone. Further clinical trials using novel drugs, altered fractionation radiotherapy and chemotherapy dose schedules, new radiotherapy techniques, and other treatment modifiers are needed to further improve the therapeutic ratio.

Antineoplastic Combined Chemotherapy Protocols↗

Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099.

PURPOSE: The Southwest Oncology Group (SWOG) coordinated an Intergroup study with the participation of Radiation Therapy Oncology Group (RTOG), and Eastern Cooperative Oncology Group (ECOG). This randomized phase III trial compared chemoradiotherapy versus radiotherapy alone in patients with nasopharyngeal cancers. MATERIALS AND METHODS: Radiotherapy was administered in both arms: 1.8- to 2.0-Gy/d fractions Monday to Friday for 35 to 39 fractions for a total dose of 70 Gy. The investigational arm received chemotherapy with cisplatin 100 mg/m2 on days 1, 22, and 43 during radiotherapy; postradiotherapy, chemotherapy with cisplatin 80 mg/m2 on day 1 and fluorouracil 1,000 mg/m2/d on days 1 to 4 was administered every 4 weeks for three courses. Patients were stratified by tumor stage, nodal stage, performance status, and histology. RESULTS: Of 193 patients registered, 147 (69 radiotherapy and 78 chemoradiotherapy) were eligible for primary analysis for survival and toxicity. The median progression-free survival (PFS) time was 15 months for eligible patients on the radiotherapy arm and was not reached for the chemo-radiotherapy group. The 3-year PFS rate was 24% versus 69%, respectively (P < .001). The median survival time was 34 months for the radiotherapy group and not reached for the chemo-radiotherapy group, and the 3-year survival rate was 47% versus 78%, respectively (P = .005). One hundred eighty-five patients were included in a secondary analysis for survival. The 3-year survival rate for patients randomized to radiotherapy was 46%, and for the chemoradiotherapy group was 76% (P < .001). CONCLUSION: We conclude that chemoradiotherapy is superior to radiotherapy alone for patients with advanced nasopharyngeal cancers with respect to PFS and overall survival.

Adolescent↗

Influence of fraction size, total dose, and overall time on local control of T1-T2 glottic carcinoma.

PURPOSE: To evaluate the influence of fraction size, overall time, total dose, and other prognostic factors on local control of T1 and T2 glottic carcinomas. METHODS AND MATERIALS: Between 1956 and 1995, 398 consecutive patients with early glottic carcinoma (315 T1 and 83 T2) were treated with once-a-day definitive radiotherapy at the University of California, San Francisco, and associated institutions. Treatment was delivered 5 days per week. Minimum tumor dose ranged from 46.6 to 77.6 Gy (median: 63 Gy). The fraction size was < 1.8 Gy in 146; 1.8-1.99 Gy in 128; 2.0-2.24 Gy in 62, and > or = 2.25 Gy in 62 patients. Overall time ranged from 34 to 75 days (median: 50 days). The majority of patients treated with a fraction size of 2.25 Gy completed therapy within 43 days. Median follow-up of all alive patients was 116 months (range 3-436 months). RESULTS: Five-year local control was 85% for T1 and 70% for T2 glottic carcinomas (p = 0.0004). For T1 lesions, within the dose and time range evaluated, there was no apparent relationship between fraction size, overall time, total dose, and local control on multivariate analysis. Treatment era was the only significant prognostic factor (p = 0.02), and anterior commissure (AC) involvement was of borderline significance (p = 0.056). Five-year local control was 77% for patients treated between 1956-1970, 89% for between 1971-1980, and 91% for between 1981-1995; 80% for patients with AC involvement and 88% for those without. For T2 lesions, prognostic factors for local control on multivariate analysis were: overall time (p = 0.003), fraction size (p = 0.003), total dose (p = 0.01), impaired vocal cord mobility (p = 0.02), and subglottic extension (p = 0.04). Five-year local control was 100% for T2 lesions treated with overall time < or = 43 days vs. 84% for overall time > 43 days; 100% for fraction size > or = 2.25 Gy vs. 44% for fraction size < 1.8 Gy; 78% for total dose > 65 Gy vs. 60% for total dose < or = 65 Gy; 79% for normal cord mobility vs. 45% for impaired cord mobility, and 58% for lesions with subglottic extension vs. 77% for those without. The severe complication rate for the entire group was low: 1.8%. CONCLUSIONS: Total dose, fraction size, and overall time were significant factors for local control of T2 but not T1 glottic carcinomas. Anterior commissure involvement was associated with decreased local control for T1 but not T2 lesions. For T1 lesions, local control improved over the treatment era. For T2 lesions, local control decreased with impaired cord mobility and subglottic extension.

Adult↗

Prognostic factors in adult soft-tissue sarcomas of the head and neck.

PURPOSE: The main objectives of this study were (a) to review the treatment results of primary head and neck soft-tissue sarcoma at our institution, (b) to identify important prognostic factors in local control and survival, and (c) to assess the efficacy of salvage therapy. METHODS AND MATERIALS: Sixty-five patients were treated at the University of California, San Francisco, between 1961 and 1993. Seventeen patients (27%) had low-grade, 10 (15%) had intermediate-grade, and 38 (58%) had high-grade sarcomas. Tumors were > 5 cm in 35 patients. Local management consisted of surgery alone in 14 patients (22%), surgery and radiotherapy in 40 (61%), and radiotherapy alone in 11 (17%) patients. The median follow-up was 64 months. RESULTS: The 5-year actuarial local control rate of the entire group was 66%. Tumor size and grade were important predictors for local control on multivariate analysis. The actuarial local control rate at 5 years was 92% for T1 vs. 40% for T2 primaries (p = 0.004), and 80% for Grade 1-2 vs. 48% for Grade 3 tumors (p = 0.01). None of the patients treated with radiotherapy alone with a dose of 50-65 Gy were controlled locally. Combined radiotherapy and surgery appeared to yield superior local control compared to surgery alone (77% vs. 59%); however, the difference was not statistically significant. The 5-year actuarial overall and cause-specific survivals were 56% and 60%, respectively. Unfavorable prognostic factors for cause-specific survival on multivariate analysis were age > 55 (p = 0.009), high tumor grade (p = 0.0002), inadequate surgery (p = 0.008), and positive surgical margins (p = 0.0009). In patients who underwent salvage therapy for treatment failure, the 5-year actuarial survival after salvage treatment was 26%. CONCLUSION: Tumor size and grade were important predictors for local control. Age, grade, adequacy of surgery, and status of surgical margins were significant prognostic factors for survival. There was a trend of improved local control with combined surgery and radiotherapy compared to either modality alone for high-risk patients. Radiotherapy alone with doses < or = 65 Gy was insufficient for control of gross disease. Aggressive salvage therapy was worthwhile in patients whose disease was uncontrolled after the initial treatment.

Adolescent↗

p53 status and prognosis of locally advanced prostatic adenocarcinoma: a study based on RTOG 8610.

BACKGROUND: The p53 tumor suppressor gene (also known as TP53) is one of the most frequently mutated genes in human cancer. Several studies have shown that p53 mutations are infrequent in prostate cancer and are associated with advanced disease. PURPOSE: We assessed the prognostic value of identifying abnormal p53 protein expression in the tumors of patients with locally advanced prostate cancer who were treated with either external-beam radiation therapy alone or total androgen blockade before and during the radiation therapy. METHODS: The study population consisted of a subset of patients entered in Radiation Therapy Oncology Group protocol 8610 ("a phase III trial of Zoladex and flutamide used as cytoreductive agents in locally advanced carcinoma of the prostate treated with definitive radiotherapy"). Immunohistochemical detection of abnormal p53 protein in pretreatment specimens (i.e., needle biopsies or transurethral resections) was achieved by use of the monoclonal anti-p53 antibody DO7; specimens in which 20% or more of the tumor cell nuclei showed positive immunoreactivity were considered to have abnormal p53 protein expression. Associations between p53 protein expression status and the time to local progression, the incidence of distant metastases, progression-free survival, and overall survival were evaluated in univariate (logrank test) and multivariate (Cox proportional hazards model) analyses. Reported P values are two-sided. RESULTS: One hundred twenty-nine (27%) of the 471 patients entered in the trial had sufficient tumor material for analysis. Abnormal p53 protein expression was detected in the tumors of 23 (18%) of these 129 patients. Statistically significant associations were found between the presence of abnormal p53 protein expression and increased incidence of distant metastases (P = .04), decreased progression-free survival (P = .03), and decreased overall survival (P = .02); no association was found between abnormal p53 protein expression and the time to local progression (P = .58). These results were independent of the Gleason score and clinical stage. A significant treatment interaction was detected with respect to the development of distant metastases: Among patients receiving both radiation therapy and hormone therapy, those with tumors exhibiting abnormal p53 protein expression experienced a reduced time to the development of distant metastases (P = .001); for patients treated with radiation therapy alone, the time to distant metastases was unrelated to p53 protein expression status (P = .91). CONCLUSIONS: Determination of p53 protein expression status yield significant, independent prognostic information concerning the development of distant metastases, progression-free survival, and overall survival for patients with locally advanced prostate cancer who are treated primarily with radiation therapy. IMPLICATIONS: The interaction of radiation therapy plus hormone therapy and abnormal p53 protein expression may provide a clinical link to experimental evidence that radiation therapy and/or hormone therapy act, at least in part, by the induction of apoptosis (a cell death program) and suggests that this mechanism may be blocked in patients whose tumors have p53 mutations.

Adenocarcinoma↗

Combined-modality therapy for head and neck cancer.

Chemotherapy, when combined with radiotherapy and/or surgery in the treatment of patients with head and neck cancer, appears to be most efficacious if it is given concurrently with radiotherapy. Concurrent chemotherapy and radiotherapy has been shown to improve locoregional control and/or disease-free or overall survival in some randomized trials. However, acute mucositis is usually increased with simultaneous drug and radiation administration, especially when more than one drug is given concurrently with radiotherapy. The optimal drug or drug combinations for use in combined-modality therapy and the optimal drug and radiation dose schedules remain to be determined. Alternating radiotherapy and combination chemotherapy may also be beneficial and needs further evaluation. Induction chemotherapy followed by definitive radiotherapy in the chemotherapy responders is an alternative treatment option for patients with locally advanced, resectable squamous cell carcinoma of the larynx or hypopharynx who desire organ function preservation. Induction and/or adjuvant chemotherapy may also decrease or delay the appearance of distant metastasis. However, induction chemotherapy has not been shown to improve locoregional control or overall survival. Further clinical trials using novel drugs, innovative radiation and drug dose schedules, and other treatment modifiers are needed to improve the therapeutic ratio.

Chemotherapy, Adjuvant↗

Cloning, mapping, and in vivo localization of a human member of the PKCI-1 protein family (PRKCNH1).

We report here the complete cDNA sequence, genomic mapping, and immunolocalization of the first human member of the protein kinase C inhibitor (PKCI-1) gene family. The predicted human protein (hPKCI-1) is 96% identical to bovine and 53% identical to maize members, indicating the great evolutionary conservation of this protein family. The hPKCI-1 gene (HGMV-approved symbol PRKCNH1) maps to human chromosome 5q31.2 by fluorescence in situ hybridization. Indirect immunofluorescence shows that hPKCI-1 localizes to cytoskeletal structures in the cytoplasm of a human fibroblast cell line and is largely excluded from the nucleus. The cytoplasmic localization of hPKCI-1 is consistent with a postulated role in mediating a membrane-derived signal in response to ionizing radiation.

Amino Acid Sequence↗

Evolution of the Radiation Therapy Oncology Group clinical trials for head and neck cancer.

During the past 25 years, the Radiation Therapy Oncology Group (RTOG) has played a major role in head and neck cancer clinical research. The major research themes for recent and currently active trials have been: (a) combined modality therapy, (b) altered fractionation radiotherapy, (c) hypoxic cell sensitizers, (d) organ preservation, (e) chemoprevention, and (f) clinical/laboratory correlations. For advanced operable disease, the RTOG showed improved local-regional control with postoperative radiotherapy as compared to preoperative radiotherapy for carcinoma of the supraglottic larynx and hypopharynx. This established the use of surgery followed by postoperative radiotherapy as the standard treatment in subsequent RTOG and Intergroup trials for operable disease. For advanced inoperable disease, the RTOG demonstrated the feasibility of testing altered fractionation radiotherapy in a multiinstitutional clinical trials setting. A Phase III trial comparing hyperfractionation and accelerated fractionation to conventional fractionation is now in progress. Phase I/II combined modality studies established the efficacy of concurrent high-dose cisplatin and radiotherapy in the treatment of advanced disease and provided the basis for further testing in Phase III trials for nasopharyngeal carcinoma, larynx preservation, and high-risk advanced operable disease. Analysis of the extensive RTOG Head and Neck Cancer database established the incidence of second malignancies and their adverse impact on patients whose initial tumors were cured by radiotherapy, and provided the basis for chemoprevention trials. Recursive partitioning analysis identified 6 distinct prognostically homogeneous patient groups based on pretreatment tumor or patient characteristics and/or treatment variables. Retrospective analysis identified tumor p105 antigen density as an independent prognostic indicator in patients irradiated for head and neck cancer. Future trials will continue to focus on the reduction of morbidity and mortality, and improvement of the quality of life of head and neck cancer patients through innovative radiotherapy delivery, multimodality approaches, use of chemical and biological modifiers, and other novel therapies, identification of clinical and biological prognostic indicators, and prevention or diminution of acute morbidity and late complications of the disease and its treatment.

Antineoplastic Agents↗

Recursive partitioning analysis of 2105 patients treated in Radiation Therapy Oncology Group studies of head and neck cancer.

BACKGROUND: The Radiation Therapy Oncology Group conducts large-scale prospective, randomized trials to test new concepts in cancer patient care and provide information about pretreatment and treatment factors that may influence outcome. METHODS: Recursive partitioning analysis (RPA) was used to examine the data derived from 2105 patients. RPA grouped patients according to the influence of tumor, of host, and of treatment variables on outcome. RESULTS: For survival, the most important factor was T classification. For lesions less than T3, the primary tumor was the next most important factor, whereas for T3 and T4 lesions the Karnofsky score was the next most predictive factor. Six distinct groups were formed by RPA, with median survivals ranging from 6.8 to 151.8 months. For local-regional control, the N classification was the most important factor. For patients with no adenopathy, T classification was the next most important factor, whereas for patients with adenopathy, the number of treatment fractions was the next most important factor. Such analysis created 5 distinct groups. In the most favorable, the median time to local-regional relapse has not yet been reached. In the least favorable group, fewer than 50% of the patients experienced complete response at any time following treatment. CONCLUSIONS: RPA clarifies the relative importance and potential interactions of pretreatment and treatment variables and should permit more accurate stratification of patients in future trials.

Carcinoma, Squamous Cell↗

New prognostic factors in nasopharyngeal carcinoma. Tumor angiogenesis and C-erbB2 expression.

BACKGROUND: This study was conducted to determine the prognostic significance of tumor angiogenesis, c-erbB2, epidermal growth factor receptor, Ki-67, and p53 for patients with nasopharyngeal carcinoma. METHODS: In this retrospective study, the authors retrieved clinical data and made immunohistochemical preparations on archival tissue specimens from 30 patients with nasopharyngeal carcinoma treated with radiation therapy at the University of California at San Francisco between 1956 and 1990. The pretreatment clinical and immunohistochemical data were correlated with cervical lymph node metastasis at diagnosis, and endpoints including development of locoregional failure, distant metastasis, disease free survival, and overall survival. RESULTS: Intense tumor angiogenesis, defined as microvessel counts for 60 or more microvessels per 200 x field correlated with the development of distant metastasis (P = 0.03), shorter overall survival (P = 0.02), and disease free survival (P = 0.05). Strong c-erbB2 expression correlated with a shorter overall survival (P = 0.02) and disease free survival (P = 0.02). Stage IV disease (P = 0.04) and the presence of cervical lymph node metastasis (P = 0.05) correlated with a shorter overall survival. A duration of symptoms of fewer than 6 months correlated with a shorter disease free survival (P = 0.05). No association was observed between any of the biologic prognostic factors and lymph node involvement or locoregional failure. CONCLUSIONS: The results of this study show that the tumor angiogenesis and c-erbB2 expression are significant prognostic indicators for patients with nasopharyngeal carcinoma. The presence of cervical lymph node metastasis, Stage IV disease, and a duration of symptoms fewer than 6 months also indicate a poor prognosis. The authors did not find any prognostic significance for epidermal growth factor receptor, Ki-67, or p53. These results suggest that tumor microvessel counts and c-erbB2 may be useful in identifying patients who may benefit from systemic chemotherapy or other novel treatment strategies.

Adolescent↗

Flutamide-induced liver toxicity including fatal hepatic necrosis.

PURPOSE: To describe hepatic injuries in three patients who received flutamide prior to and during radiation treatment to make radiation oncologists aware of the need for careful monitoring of liver function during use of this drug. METHODS AND MATERIALS: The records of three patients who developed abnormal liver function tests while undergoing total androgen suppression (TAS), as well as the literature concerning flutamide toxicity were reviewed and summarized. RESULTS: Three of 34 patients treated with a TAS regimen incorporating flutamide developed significant hepatic abnormalities: elevated transaminases [2] and fatal hepatic necrosis [1]. Following the discontinuation of flutamide, two patients recovered fully. Unfortunately, the third patient's hepatic function continued to deteriorate, which culminated in his death. Transient elevations in serum transaminases, which do not exceed four times the upper limits of normal, are common and apparently without clinical significance. Unfortunately, idiosyncratic serious and/or fatal liver damage can occur. Significant liver toxicity may be obviated by monitoring of liver function tests (LFT) early in the course of flutamide therapy. CONCLUSION: The incidence of hepatic toxicity associated with flutamide may be higher than previously suggested. To prevent the development of serious hepatic dysfunction, all patients receiving flutamide should be monitored clinically for signs and symptoms referable to hepatic injury and with serial LFT. We recommend baseline LFT followed by serial LFT at weeks 2, 4, 6, and 8 from the start of treatment with flutamide. Flutamide should be stopped promptly if significant liver abnormalities are detected.

Adenocarcinoma↗

Frequent novel DNA copy number increase in squamous cell head and neck tumors.

We have undertaken a study of DNA copy number changes in head and neck squamous cell carcinomas to identify novel DNA copy number changes and to determine the significance of previous findings of cytogenetic alterations in cultured cells. Comparative genomic hybridization was performed on genomic DNA extracted from ten tumors. A novel copy number gain on chromosome 3q26-27 and a loss of chromosome 3p were found at high frequency (> or = 50% of tumors). Many other novel chromosomal copy number changes were identified but occurred at a lower frequency. In addition, our data confirm that DNA copy number changes that frequently occur in cultured cells, such as loss of chromosome 3p, also occur in tumors. Frequently altered loci may encode oncogenes or tumor suppressor genes involved in head and neck squamous cell carcinoma tumorigenesis.

Aged↗