Expression of epidermal growth factor receptor in head and neck cancers correlates with clinical progression: a multicentre immunohistochemical study in the Asia-Pacific region.

AIMS: With ongoing efforts to target the epidermal growth factor receptor (EGFR)-mediated tumour growth in the treatment of selected human malignancies, there is a need to determine the expression levels of EGFR and to evaluate its prognostic value in various malignancies in the Asia-Pacific region. METHODS AND RESULTS: A total of 172 patients with head and neck squamous cell carcinomas from Australia, Hong Kong, Singapore, and Taiwan were selected for EGFR detection. Immunohistochemical staining was performed to evaluate EGFR expression. EGFR expression was present in 88.4% (152/172) of all cases tested. Specifically, EGFR expression was found in 91.3% (42/46), 84.6% (22/26), 84.1% (37/44), 96.0% (24/25), and 87.1% (27/31) cases of head and neck squamous cell carcinomas from the oral cavity, oropharynx, nasopharynx, hypopharynx, and larynx, respectively. The results demonstrate a stronger EGFR expression in T4 tumours (P=0.017) and later clinical stages (P=0.016). No significant correlation was seen with risk factors, primary tumour site and ethnicity. CONCLUSIONS: The majority of head and neck squamous cell carcinomas express EGFR, indicating the importance of studying the efficacy of anti-cancer therapy through this pathway. The results also show similar rates of receptor expression in head and neck squamous cell carcinoma patients from our region compared with other parts of the world.

Curcumin-containing diet inhibits diethylnitrosamine-induced murine hepatocarcinogenesis.

Curcumin has been widely used as a spice and coloring agent in foods. Recently, curcumin was found to possess chemopreventive effects against skin cancer, forestomach cancer, colon cancer and oral cancer in mice. Clinical trials of curcumin for prevention of human cancers are currently ongoing. In this study, we examine the chemopreventive effect of curcumin on murine hepatocarcinogenesis. C3H/HeN mice were injected i.p. with N-diethylnitrosamine (DEN) at the age of 5 weeks. The curcumin group started eating 0.2% curcumin-containing diet 4 days before DEN injection until death. The mice were then serially killed at the scheduled times to examine the development of hepatocellular carcinoma (HCC) and changes in intermediate biological markers. At the age of 42 weeks, the curcumin group, as compared with the control group (DEN alone), had an 81% reduction in multiplicity (0.5 versus 2.57) and a 62% reduction in incidence (38 versus 100%) of development of HCC. A series of intermediate biological markers were examined by western blot. While hepatic tissues obtained from the DEN-treated mice showed a remarkable increase in the levels of p21(ras), PCNA and CDC2 proteins, eating a curcumin-containing diet reversed the levels to normal values. These results indicate that curcumin effectively inhibits DEN-induced hepatocarcinogenesis in the mouse. The underlying mechanisms of the phenomenon and the feasibility of using curcumin in the chemoprevention of human HCC should be further explored.

Malignant thyroid teratoma of an adult: a long-term survival after chemotherapy.

Adult primary malignant teratoma of the thyroid is a rare disease that has a poor outcome despite aggressive therapy. A 32-year-old woman underwent a simple lobectomy of the thyroid for a progressively enlarged nodule in August 1990. Pathologic assessment of the tumor revealed a malignant teratoma. The physical examinations and image studies failed to find tumor in other sites. She subsequently received 6 courses of chemotherapy with cisplatin, etoposide, and bleomycin. She experienced a complete response to chemotherapy and remained disease-free for 6.5 years. This tumor must be included in the differential diagnosis of a thyroid tumor and may be treated as a testicular germ-cell tumor for which chemotherapy may be recommended.

Weekly CAF chemotherapy for advanced breast cancer patients.

In a prospective phase II study, 102 women with advanced breast cancer were treated with low doses of cyclophosphamide, Adriamycin and 5-fluorouracil (CAF) at weekly intervals by intravenous injection. Seventy-five patients were evaluable for treatment response and the overall response rate was 52% (95% confidence interval, 41-63%). Of the evaluable patients, 15% had complete response and 37% had partial response. The median survival after therapy was 15.6 months, the median time to progression was 6.8 months and the median duration of response was 9.1 months. The main toxicities were mild vomiting and moderate myelosuppression. There was only 1 patient who experienced heart failure. Weekly CAF appears to have an efficacy with tolerable side effects comparable to standard CAF with an every-3-week schedule.

Intensive chemotherapy plus recombinant human granulocyte-colony stimulating factor support for distant metastatic nasopharyngeal carcinoma. A preliminary report.

Nasopharyngeal carcinoma (NPC) has been shown to be highly responsive to chemotherapy. The major limiting toxicity was myelotoxicity. Recently, the role of granulocyte colony-stimulating factor (G-CSF) in reducing chemotherapy-induced neutropenic sepsis has been well established. In this study, we tested whether recombinant human G-CSF (rhG-CSF) could effectively support the bone marrow function in both previously untreated and pretreated metastatic NPC patients receiving intensive chemotherapy. Twelve patients with distant metastatic disease, 5 newly diagnosed (group A) and 7 pretreated patients (group B), were enrolled to receive BEC (bleomycin, epirubicin and cisplatin), followed by rhG-CSF support (50 microg/m2 s.c. daily for 10 days) every 4 weeks for two cycles. Four patients in group A completed the treatment as scheduled while only 2 patients in group B did. After the first treatment cycle, 6 patients (50%) had grade III-IV myelosuppression. Five of the patients were from group B. The mean values of the white cell count nadir were 2,680 (range 1,200-3,700) in group A and 1,343 (range 400-2,900) in group B (p = 0.0386). Neutropenia-associated fever occurred in 7 patients, 6 of whom had received previous treatment. There were 2 deaths due to toxicity, and both patients had liver metastases within 6 months following radiation. After 24 months of follow-up, only 1 patient is still alive. Our preliminary results suggest that in previously treated metastatic NPC patients, bone marrow suppression is still the major limiting toxic side effect of aggressive chemotherapy, especially for those patients with liver recurrences within 6 months after irradiation and despite rhG-CSF support.

Clinical trial of low-dose rHuG-CSF in neutropenic cancer patients following anti-cancer chemotherapy.

Low-dose, subcutaneous recombinant human granulocyte colony-stimulating factor (rHuG-CSF, Lenograstim) was administered to 40 cancer patients (17 men, 23 women) enrolled from two medical centers to verify its clinical effectiveness and safety. The patients' mean age was 50.3 +/- 14.9 years. In this study, there were 20 patients with non-Hodgkin's lymphoma, 10 with breast cancer and 10 with various other solid tumors. The patients first received a course of chemotherapy without rHuG-CSF (control cycle). All patients had at least one episode of neutropenia or leukopenia during the control cycle. rHuG-CSF (2 micrograms/kg/day) was given subcutaneously for 10 days during the study cycle starting on the fourth day of chemotherapy. The nadirs of absolute neutrophil counts (ANC) were 1.8 +/- 0.25 x 10(9)/L and 0.27 +/- 0.05 x 10(9)/L for the rHuG-CSF cycle and pre-rHuG-CSF control cycle, respectively. The number of days of ANC < 1 x 10(9)/L were 1.03 +/- 0.29 and 7.38 +/- 0.58 for rHuG-CSF and control cycles, respectively. The duration from nadir to recovery of ANC (> or = 2 x 10(9)/L) was 9.68 +/- 1.15 days in the rHuG-CSF cycle, vs 22.53 +/- 1.03 days in the control cycle (p < 0.0001). No patient withdrew from the study. Adverse events were mild, with 12.5% to 40% of patients developing myalgia, general malaise, back pain, anorexia or fever. These side-effects were tolerable in all cases. The biochemical abnormalities were subtle and negligible. rHuG-CSF 2 micrograms/kg/day given subcutaneously for 10 days beginning on the fourth day of chemotherapy is very effective (90%), safe and convenient.

Correlation between computed tomographic density of lymph node metastases and response to cisplatin-based chemotherapy in patients with head and neck squamous cell carcinoma in an area in which betel quid chewing is prevalent.

BACKGROUND: Identifying the factors predicting response to chemotherapy is important for patients with head and neck squamous cell carcinoma (HNSCC). It allows more rational selection of subsets of patients who may benefit from multidisciplinary treatment. Correlation of lymph node density in contrast-enhanced computed tomographic (CT) scans of HNSCC with response to chemotherapy was observed in the recent literature. This prospective study was designed to validate this clinical issue. METHODS: From January 1992 to March 1995, 71 patients with untreated HNSCC were included in this study in which the following criteria were met: 1) a lymph node > 3 cm by physical examination or > or = 2 cm by scanographic examination; 2) clinically evaluable disease treated by cisplatin-based neoadjuvant chemotherapy; and 3) availability of a pretherapeutic contrast-enhanced CT scan showing the cross-sections of relevant lymph node metastases. The density of the largest lymph node was compared with that of the nuchal muscles by a radiologist blinded to the patient's therapeutic outcome. A lymph node was classified as hypodense if more than 33% of the lymph node surface area was comprised of a hypodense zone, and isodense if less than a third of the lymph node surface area was comprised of a hypodense zone. RESULTS: Fifty-one patients (72%) had the largest lymph node classified as hypodense, and 63 patients (89%) were found to have extranodal spread (ENS) in the relevant lymph nodes. Fifty-nine patients were betel quid chewers. Lymph node density was not related to T classification, primary site, or histologic differentiation of the primary tumor. There was also no correlation between lymph node density and lymph node N classification. The lymph node chemotherapy response rate was 35% (7 of 20) of the isodense group and 47.1% (24 of 51) of the hypodense group (P = 0.36). ENS was found to have no impact on the chemotherapy response. CONCLUSIONS: Computed tomographic density of lymph node metastases did predict chemotherapy response in the HNSCC patients in the current study from an area in which betel quid chewing is prevalent.

Prognostic factors of locoregionally recurrent nasopharyngeal carcinoma--a retrospective review of 182 cases.

Locoregional relapse is the major cause of failure of nasopharyngeal carcinoma (NPC) after radical radiation therapy. The prognosis of such patients is dismal, and the factors related to the outcome are not well identified. Between January 1983 and December 1989, 1,168 new patients with biopsy-proven NPC were seen at this hospital. Eight hundred and eighty-three of these patients were treated uniformly with radical external irradiation and intracavitary treatment with or without chemotherapy. The clinical courses, retreatment outcomes, and prognostic factors for locoregional relapse and subsequent distant metastasis were analyzed. During the follow-up period of 3-10 years or until death, 182 patients (20.6%) developed locoregional relapses without distant metastasis initially. T stage and age were significant prognostic factors for locoregional recurrence. In contrast, histopathologic subtype, N stage, sex, and systemic chemotherapy were not. There were 36 patients (19.8%) who developed subsequent distant metastasis with or without retreatment. The median time from locoregional relapses to distant metastasis was 6 months in this study, and bone was the most frequent and the earliest site of distant metastasis. The N stage at diagnosis, the initial disease-free interval, the presence of neck nodal disease at relapse, and age were the significant factors for predicting the subsequent distant metastasis in locoregionally recurrent NPC patients. We recommend that additional systemic chemotherapy should be considered for retreatment of locoregional relapsed NPC, not only for enhancement of local control but also for eradicating microscopic metastasis as anticipated.

Newly established MST-1 tumour cell line and tumour-infiltrating lymphocyte culture from a patient with soft tissue melanoma (clear cell sarcoma) and their potential applications to patient immunotherapy.

The establishment and characterisation of paired autologous tumour cell line (MST-1) and tumour-infiltrating lymphocyte (TIL) culture from a tumour mass of a 14-year-old Taiwanese girl with soft tissue melanoma are described. MST-1 cells grown in vitro were heterogeneous in morphology, ranging from floating round cells, loosely attached round/oval or elongated cells with prominent pseudopod-like processes, to well-attached spindle and elongated dendritic cells without obvious pseudopods. Immunostaining revealed that major melanoma-associated antigens, such as S100 protein, HMB-45, melanotransferrin, chondroitin sulphate proteoglycan, and the gangliosides GD2 and GD3, were consistently expressed by the tumour tissue, severe combined immunodeficiency (SCID) mouse xenograft and derived cell lines. Flow cytometric analysis of the tumour DNA content showed an index of 1.8 relative to normal peripheral blood lymphocyte DNA. Chromosome analysis revealed all cells at a hypotetraploid level with several clonal chromosome aberrations, including deletions at 10p and 12q, an addition at 12q, translocations t(1;14) and t(5;6). Electron microscopy showed melanosome structures. This observation and the expression of the major melanoma-associated antigens were all indicative of the melanocytic origin of MST-1 tumour. Interleukin-2 (IL-2) expanded TILs had the predominant CD8+ phenotype and the capacity to lyse cells of the cultured autologous tumour. The availability of the soft tissue melanoma cell line, the SCID mouse xenograft tumour system as well as autologous TILs described herein would provide useful materials for identifying T-cell-defined antigens as well as a model system for devising individualised cancer biotherapeutic strategies. This cell line can also be used for further studies aimed at uncovering the histogenesis of this rare cancer.

Cisplatin and 5-fluorouracil as neoadjuvant chemotherapy: predicting response in head and neck squamous cell cancer.

In order to prospectively evaluate the efficacy, toxicity and predictive factors of response to neoadjuvant chemotherapy, a total of 120 patients with head and neck squamous cell cancer diagnosed from January 1992 to November 1993 were enrolled in this study. There were 118 male and 2 female patients, with a median age of 51 years (range 30-74 years). The primary sites were the oral cavity (77), oropharynx (15), hypopharynx (25) and larynx (3). Betel quid chewing was habitual in 91% of patients. All patients were previously untreated, and 94% had stage III or IV disease. Chemotherapy was given in two or three courses to 96 patients who were then assessed for response rate and predictive factors. The chemotherapy regimen consisted of cisplatin 100 mg/m2/day on day 1 and 5-fluorouracil (5-FU) 1 g/m2/day intravenous infusion continuously for 4 to 5 days for 4 weeks. The overall chemotherapy response rate was 56%, with a 3% complete response. By univariate analysis, both the T-stage and tumor volume were significant for predicting the response of the primary site. The age, histologic differentiation, tumor location and N-stage were unpredictive for response. The nodal response (43%) was less than that of the primary site (68%). By multivariate analysis, only the tumor volume (> or = 50 cm3) and the presence of nodal metastases were predictive for the combined TN response. Based on the World Health Organization toxicity criteria, 49 patients experienced grade 3 to 4 mucositis, and 24 patients had grade 3 to 4 vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Transient neurological disturbances induced by the chemotherapy of high-dose methotrexate for osteogenic sarcoma.

Temporary neurologic abnormalities were observed in one out of 23 patients undergoing chemotherapy with high-dose methotrexate (HD-MTX) for osteogenic sarcoma. This patient developed sequential symptoms including alternative hemiparesis, dysarthria and altered consciousness 5 days after the second course of HD-MTX (8 gm/m2 by 6 h continuous infusion) with leucovorin rescue. Laboratory evaluations disclosed normal electrolytes, hemograms and non-toxic serum MTX levels at the onset of the symptoms. Computed tomography of the brain was normal but electroencephalography showed focal theta and delta slow waves over the right temporal-parietal-occipital area. The neurological symptoms resolved completely within 72 h.

Vascular contractile properties in hypertension. I. A study of testing methods.

Abnormal contractile responses of blood vessels are observed widely in several hypertension models and are assumed to play a role in the etiology of essential hypertension. Inconsistent reports also exist due to different animals, preparations, and experimental techniques employed. In this investigation, we compared vascular response of normotensive Wistar-Kyoto rat (WKY) with that of spontaneously hypertensive rat (SHR) employing two experimental methods. Thoracic aorta obtained from age-matched animals were contracted by norepinephrine (NE) with either--single-dose method or cumulative-dose method. Differences in both reactivity (maximal tension) and sensitivity (ED50) to NE were observed. Although no significant differences were found between WKY and SHR with either method, the choice of the method employed could affect the outcome. For aorta from WKY, the reactivity to NE was similar for both methods; however, for aorta from SHR, the reactivity obtained by cumulative-dose method was significantly higher. Furthermore, the cumulative-dose method yielded higher sensitivity in both WKY and SHR when compared with that obtained by single-dose method. Taken together, the cumulative-dose method appeared to be a more sensitive method to determine contractile response. Nevertheless, no significant difference in either reactivity or sensitivity to NE in aorta was detected between WKY and SHR when cumulative-dose method was employed. These data indicate that aorta do not exhibit abnormal response to NE in SHR, consistent with earlier findings that not all tissue preparations behave similarly.

Prognosis of thymic carcinoma: analysis of 16 cases.

Primary thymic carcinoma is a rare malignant neoplasm which arises from the thymic epithelium. Between May 1982 and September 1990, 16 patients with thymic carcinomas, diagnosed at Chang Gung Memorial Hospital, were reviewed. Their ages ranged from 19 to 75 years, with a median of 40 years. Males predominated (male to female ratio was 11:5). The most common presenting symptoms were chest pain, cough, body weight loss and dyspnea. No paraneoplastic syndromes were seen. Chest roentgenograms of 15 patients revealed a mediastinal mass, but a definitive diagnosis could not be made until surgery. Adjacent mediastinal tissues were invaded, or adhered to, by all the tumors. Six distinct histologic types were found, squamous cell carcinoma being the most common (seven cases). The primary treatment of surgical resection was attempted in 14 patients, but only in five cases could the tumors be completely resected; two had a biopsy only. Radiotherapy, with or without chemotherapy, given postoperatively, achieved additional local control in seven of the nine partially resected patients (77%). Distant metastasis occurred in nine of 16 patients (56%). Lymph nodes, bone and lung were the most common metastatic sites. Chemotherapy with cisplatin and/or adriamycin-based regimens was given to patients who had distant metastasis, but the responses were unsatisfactory. The overall survival at one, three and five years was 88%, 51% and 31%, respectively. The median survival was 30 months. The median survival of patients with pure squamous cell carcinoma (> 49 months) was superior to that of patients with other histologic types (18 months; p < 0.01).

Meningeal carcinomatosis from solid tumors: clinical analysis of 42 cases.

From January 1984 to June 1990, we observed 42 patients with meningeal carcinomatosis, 20 men and 22 women, aged 21 to 80 years (median age, 53 years). The two most common primary malignancies were lung cancer (50%) and breast cancer (31%). Sixty-four per cent was adenocarcinoma. On the first lumbar puncture, 86% had malignant cells in the cerebrospinal fluid. The findings of brain computed tomography were hydrocephalus (62%), contrast enhancement in the cerebral sulci or basal cisterns (31%), concomitant parenchymal metastases (15%) and normal scan (18%). In five out of seven cases, myelography showed irregular filling defects over the spinal cord or cauda equina. Treatment results were evaluated in 24 patients. Eight received radiation therapy (RT) alone, and 16 had combined therapy with RT plus intrathecal methotrexate (IT MTX). Of the patients who received RT alone, only one patient with lung carcinoma was stabilized clinically. Of the cases receiving combined therapy, seven improved clinically. Six of these were patients with breast carcinoma who received IT MTX via Ommaya reservoir. The latter had a median survival of 23 weeks. The follow-up period of the entire group of patients ranged from one day to 50 weeks. The median survival was four weeks. Based on this study, combined therapy with RT and IT MTX is indicated for breast carcinoma with meningeal carcinomatosis, but the therapeutic effects are uncertain for lung carcinoma and other malignancies.

Contribution of glutathione and glutathione-dependent enzymes in the reversal of adriamycin resistance in colon carcinoma cell lines.

Four human colon cancer cell lines (SW620, LS 180, DLD-I, and HCT-15) and sub-lines isolated in vitro by selection with Adriamycin were studied for reversal of intrinsic and acquired Adriamycin resistance, using buthionine sulfoximine (BSO) to deplete cellular glutathione alone and in combination with the P-glycoprotein antagonist verapamil. GSH levels varied among the parental cell lines but did not increase with resistance. In the parental SW620, DLD-I and HCT-15 and their drug-resistant derivatives, there was no relation between the effect of the glutathione-depleting agent BSO, the mRNA expression of both selenium-dependent glutathione peroxidase (GPx) and glutathione S-transferase pi (GST pi), bulk glutathione S-transferase (GST) activity, and the degree of resistance. However, in LS 180 and its derivative sub-lines, which do not principally rely on P-glycoprotein (Pgp) for Adriamycin resistance, treatment with BSO demonstrated a relatively diminished GSH depletion and enhanced recovery. In comparison with the other acquired cell lines, BSO specifically reversed acquired resistance in the LS 180 Adriamycin-resistant subline (LS 180 Ad150) after short-term drug exposure. Furthermore, the LS 180 Ad150 cells demonstrated an increase in both GPx and GST pi mRNA expression. These observations suggest that glutathione-mediated detoxification of Adriamycin may play a role in the resistance of this sub-line. Verapamil enhanced Adriamycin cytotoxicity 1.2- to 12-fold in the intrinsically resistant cells and as much as 15-fold in cell lines with acquired resistance. Combination of BSO with verapamil resulted in additive, but not synergistic, reversal of resistance. The results underscore the complex nature of Adriamycin resistance, and suggest a role for drug-resistance-modulating agents in the treatment of colon carcinoma.

P-glycoprotein expression and schedule dependence of adriamycin cytotoxicity in human colon carcinoma cell lines.

Four human colon cancer cell lines (SW620, LS 180, DLD-I, and HCT-15) and Adriamycin-resistant sub-lines with varying degrees of P-glycoprotein expression were studied to evaluate the reversibility of Adriamycin resistance in human colon cancer. Two groups of cell lines were studied. In the first, including a series of Adriamycin-resistant SW620 and DLD-I sub-lines, and in parental HCT-15 cells, P-glycoprotein has a major role in Adriamycin resistance, as evidenced by a correlation between Adriamycin resistance, expression of the multidrug-resistance gene mdr-I and its product, P-glycoprotein (Pgp), decreased drug accumulation and reversibility by verapamil. In these cell lines, increasing doses of verapamil are required to fully reverse increasing levels of resistance. In the second group, including parental SW620, DLD-I and LS 180 cells and Adriamycin-selected LS 180 sub-lines, P-glycoprotein does not have a major role in Adriamycin resistance. There was correlation between the schedule dependence of Adriamycin cytotoxicity and the role of P-glycoprotein in modulating resistance. In the cell lines in which P-glycoprotein was a major determinant of Adriamycin resistance, the drug exposure (defined as the product of the concentration and the time of treatment) needed to achieve a given percent cell kill was reduced as much as 9-fold when cells were treated for 7 days as compared with 3 hr. By comparison, in cell lines in which P-glycoprotein played a lesser role, the drug exposure necessary to achieve a given percent kill increased under conditions of continuous treatment. In some human colon carcinoma cell lines Pgp appears to play a significant role in resistance to Adriamycin, and this can be overcome by the use of competitive inhibitors of Pgp. The increased sensitivity with continuous treatment observed in cell lines with P-glycoprotein-mediated resistance suggests that administration of drugs by continuous infusion may be valuable in reversing clinical drug resistance mediated predominantly by P-glycoprotein.

Resistance of a human ovarian cancer line to 5-fluorouracil associated with decreased levels of 5-fluorouracil in DNA.

Two human ovarian cancer cell lines were established from a patient before (PEO1) and after (PEO4) the onset of resistance to 5-fluorouracil (5-FU)/cisplatin-based chemotherapy. Using growth inhibition assays, we determined that the PEO4 line was almost 5-fold more resistant to 5-FU than the PEO1 line. The addition of either 1 or 20 microM leucovorin did not enhance the growth-inhibitory effects of 5-FU against the resistant PEO4 line. In characterizing the potential mechanisms of 5-FU resistance, we found no differences in thymidylate synthase activity between the two lines using both the 5-fluoro-2'-deoxyuridine-5'-monophosphate-binding and catalytic assays. A 4-hr exposure to 1 microM 5-FU resulted in greater ternary complex formation in the resistant line, and we observed no differences between the two lines in 5-FU incorporation into RNA. However, a 4-hr exposure to 1 microM [3H]5-FU resulted in a 3-fold decrease in 5-FU accumulation in the DNA of the resistant PEO4 line. Cesium sulfate gradient centrifugation was used to more accurately separate and analyze for DNA-incorporated 5-FU metabolites and confirmed that the absolute level of 5-FU in the DNA of the PEO4 cells was markedly decreased (6.5-fold) compared with that of the sensitive PEO1 cell line. Moreover, time course studies demonstrated that the accumulated 5-FU in the DNA of the PEO4 cells was more rapidly removed compared with that in the PEO1 cells. Our findings suggest that decreased 5-FU levels in DNA, in part due to an enhanced removal from DNA, represent a mechanism by which the human ovarian cancer PEO4 line expresses decreased sensitivity to 5-FU.

Epidemiologic characteristics and multiple risk factors of stomach cancer in Taiwan.

Both descriptive and analytical studies were carried out to examine epidemiologic characteristics and multiple risk factors of stomach cancer in Taiwan. The age-adjusted mortality rate of stomach cancer has been decreasing since the early 1970s for both males and females. The male-to-female ratio of the disease has remained around 2:1 in the past three decades. Comparison of the incidence of stomach cancer among Chinese in different countries showed a much lower incidence among Chinese in the USA than those in southeastern Asia. A hospital-based matched case-control study carried out in Taipei metropolitan areas showed a positive association of stomach cancer with blood type A, chronic gastric diseases, cigarette smoking, alcohol drinking, green tea drinking as well as consumption of salted meat, cured meat, smoked food, fried food and fermented beans. There was also a significant negative association between the disease and the consumption of milk.

Epidemiologic characteristics and multiple risk factors of lung cancer in Taiwan.

The specific aim of this study was to examine epidemiologic characteristics and multiple risk factors of lung cancer in Taiwan. The age-adjusted mortality from lung cancer has been increasing since the early 1950s with a constant male-to-female ratio of around 2.0. International comparison of cumulative mortality from lung cancer showed a much lower male-to-female ratio in Chinese than in other populations. Significantly high mortality from lung cancer was observed in highly urbanized cities and the endemic area of chronic arsenicism in Taiwan. Significant associations of active and passive cigarette smoking with epidermoid carcinoma, small cell carcinoma and adenocarcinoma of the lung were observed in a hospital-based case-control study carried out in Taipei metropolitan areas. Alcohol drinking, coffee drinking and various types of indoor air pollution were not related to lung cancer after the cigarette smoking habit was adjusted through a multiple logistic regression analysis.

Effect of glutathione on DNA repair in cisplatin-resistant human ovarian cancer cell lines.

We have studied the effect of glutathione reduction by buthionine sulfoximine (BSO), a specific inhibitor of gamma -glutamyl cysteine synthetase, on DNA repair after cisplatin damage in an ovarian cancer cell line with in vitro induced resistance to cisplatin. In addition, we have examined the effect of aphidicolin, a specific inhibitor of DNA polymerase alpha, in combination with BSO on cisplatin-associated DNA repair. BSO treatment was found to partially inhibit DNA repair, and the addition of aphidicolin caused nearly a 100% inhibition in DNA repair activity. Treatment of cells with glutathione ester after BSO resulted in complete recovery of DNA repair activity or partial recovery if aphidicolin was present. The significance of these results to the chemosensitizing effects of BSO medicated glutathione reduction is discussed.