Biomedical subjects

N Voravud

Publications and source records attributed to N Voravud.

At least 19 recordsLinked to original sources

PubMed2005

High frequency of mutation of epidermal growth factor receptor in lung adenocarcinoma in Thailand.

Recent reports have suggested influences of racial difference on the frequency of mutation of EGFR in lung cancer. We therefore sought to characterize the frequency and pattern of mutation of EGFR in lung adenocarcinoma in Thai patients. Overall, EGFR catalytic domain mutations were detected in 35/61 (57.4%). We found 29/60 (48.3%) of exon 19 deletions, 5/54 (9.3%) of exon 21 point mutations, and 1/54 (1.9%) of double-mutation of both exons. The presence of these mutations was significantly associated with non-smoking habit. In summary, we report a strikingly high prevalence of mutation of EGFR in Thai lung adenocarcinoma, which may explain the high response rate to the treatment with TKI among Asian populations.

Adenocarcinoma↗

PubMed2001

Cytochrome P450 2E1 polymorphism and nasopharyngeal carcinoma development in Thailand: a correlative study.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a rare tumor in most parts of the world but occurs at relatively high frequency among people of Chinese descent. The cytochrome P450 2E1 enzyme (CYP2E1) is responsible for the metabolic activation of nitrosamines, and has been shown to be a susceptibility gene for NPC development in Taiwan [RR = 2.6; 95%CI = 1.2-5.7]. Since there has been only one report of this link, it was decided to investigate the susceptibility of CYP2E1 to NPC development in other populations. Therefore, the correlation between the RsaI polymorphism of this gene and NPC was studied in-patients including Thai and Chinese in Thailand. The present study comprised 217 cases diagnosed with NPC and 297 healthy controls. RESULTS: Similar to the result found in Taiwanese, a homozygous uncut genotype demonstrated a higher relative risk both when all cases were analyzed [RR = 2.19; 95%CI = 0.62-8.68] or individual racial groups, Thai [RR = 1.51; 95%CI = 0.08-90.06] or Chinese [RR = 1.99; 95%CI = 0.39-10.87]. The ethnicity-adjusted odds ratio is 2.39 with 95%CI, 0.72-7.89. CONCLUSIONS: Though our finding was not statistically significant due to the moderate sample size of the study, similarity to the study in Taiwan with only a slight loss in precision was demonstrated. The higher RR found for the same genotype in distinct populations confirmed that CYP2E1 is one of several NPC susceptibility genes and that the RsaI minus variant is one mutation that affects phenotype.

Asian People↗

PubMed2001

Human papillomavirus DNA in plasma of patients with cervical cancer.

BACKGROUND: Human papillomavirus (HPV) is a crucial etiological factor for cervical cancer (CC) development. From a diagnostic view-point, the consistent presence of HPV in CC allows the viral DNA to be used as a genetic marker. The aims of this study were to evaluate the presence, physical status and clinical significant of HPV DNA in circulation of CC patients. RESULTS: Whereas 6 out of 50 (12%) HPV positive CC patients revealed plasma HPV DNA, it was detected in none of 20 normal controls or 13 HPV negative CC cases. The plasma DNA exhibited an HPV type identical to the HPV in the primary tumors and the DNA from both sources was integrated into host genome. Interestingly, several findings suggested an association between plasma HPV DNA and metastasis. First, three of the HPV DNA positive cases were CC patients with clinical stage IVB or recurrence with distance metastases (P = 0.001, RR = 15.67). Second, the amount of plasma HPV DNA from metastatic patients to be three times more than three other patients without metastases. Finally, the later cases had tendency to develop recurrence distant metastases within one year after complete treatment when compared with other HPV associated CC patients with the same stage but without the present of plasma HPV DNA. CONCLUSIONS: The plasma HPV DNA originated from the CC, was associated with metastasis and could be used as a marker representing the circulating free CC DNA.

Age Factors↗

PubMed2001

Ratio of baseline erythropoietin (EPO) level and corrected reticulocyte count as an indicator for a favourable response to recombinant human erythropoietin (rhEPO) therapy in anaemic cancer patients.

PURPOSE: Recently, recombinant human erythropoietin (rhEPO) was introduced for the management of anemia in malignancy. To identify an indicator for a favourable response to rhEPO, 28 anaemic cancer patients undergoing chemotherapy and treated with rhEPO were evaluated. METHODS: Patients were classified into responder (16 of 28, 57%) and nonresponder (12 of 28, 43%) groups according to their responses to rhEPO therapy (response being defined as an increase in Hb level of > 2 g/dl from baseline without blood transfusion). RESULTS: Treatment with rhEPO showed significant improvements in the red blood cell (RBC) count, haemoglobin (Hb), packed cell volume (PCV), and reticulocyte count (ret. count) after 4 weeks. Upon analysing the baseline value of the EPO level and the corrected ret.count in these two groups, we found that the ratio of the EPO level and the corrected ret.count (EPO/ret.count) demonstrated a statistical significance (P = 0.03) in the prediction of response to rhEPO therapy. This ratio showed a sensitivity of 87.5%, specificity of 66.7%, and overall accuracy of 78.6%. CONCLUSION: Our study suggested that the baseline ratio of EPO/ret.count should be used as an indicator for a favourable response to rhEPO therapy.

Adult↗

PubMed2001

Clinical significance of p53 antigen and anti-p53 antibodies in the sera of hepatocellular carcinoma patients.

BACKGROUND: To analyze the clinical significance of serum p53 protein and anti-p53 antibodies as serological markers for hepatocellular carcinoma (HCC). METHODS: We studied clinical data, i.e., age, sex, etiology, serum alpha-fetoprotein (AFP) level. TMN staging, and Okuda staging in 141 patients with HCC. The sera of these patients were analyzed for serum p53 protein and serum anti-p53 antibodies by enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum p53 antigen and serum anti-p53 antibodies were detected in the sera of 32 of the 141 (22.7%) patients and 26 of the 141 patients (18.4%), respectively. Of note, the HCC patients who were positive for p53 antigen (32/141) had no circulating anti-p53 antibodies. When both these groups of patients were combined as a serum p53 status-positive group, the total number in this group was 58 (41.1 %). Positive status of p53 was not associated with age (P = 0.206), serum alpha-fetoprotein level (P = 0.851). Okuda staging (P = 0.243), or survival (P = 0.078), but was correlated significantly with TMN staging (P = 0.049). Interestingly, a shorter survival time (mean, 3.9 months) was noted in the serum p53 status-positive group. in comparison with the longer survival time (mean, 6.5 months) in the serum p53 status-negative group. CONCLUSIONS: Combination of the detection of serum p53 antigen and antibodies by ELISA may represent a suitable noninvasive investigation in assessing the clinical implications and prognoses of patients with HCC.

Adult↗

PubMed2000

Outcomes of primary hepatocellular carcinoma treatment: an 8-year experience with 368 patients in Thailand.

BACKGROUND AND AIMS: Primary hepatocellular carcinoma (HCC) is common in Thailand and its prognosis is extremely poor. Hepatic resection and liver transplantation are modes of curative therapy and various therapies have been developed to treat inoperable HCC. This study was performed to determine the outcome of therapy and to identify prognostic factors for survival among Thai patients with HCC. METHODS: Three hundred and sixty-eight patients with tissue-proven or serodiagnosed HCC were studied. Differences in laboratory investigations, patient survival, treatment outcomes and prognostic factors were analysed. The Kaplan-Meier method and the log-rank test were used to calculate and compare survival of patients receiving different therapies. RESULTS: Of the 368 patients 317 were males (86.1%, M: F ratio 6.2:1). The median age of all patients was 52 years range (2-85 years). Fifty-nine patients were specifically treated and 209 were conservatively treated. Among those tested, 70% had hepatitis B virus-related HCC. The overall median survival (range) after diagnosis and that of the treated and untreated patients were 5.6 (0-92.1), 9.0 (0-92.1) and 2.3 (0-25.9) months, respectively. More than 50% of the Okuda I patients survived beyond 30 months. The Okuda II and III patients had a median survival (range) of 5.7 (0.1-75.2) and 1.6 (0.1-25.9) months, respectively. Those patients treated by surgery, transcatheter oil chemoembolization and systemic chemotherapy had a better survival rate than did the conservatively managed patients. Surgery was found to be a better treatment than systemic chemotherapy. However, no differences between other pairs of treatment groups were identified. Subgroup analysis of the Okuda II group patients revealed the same results. Independent predictors of death were multiple lesions, advanced Okuda stage and treatment modality. CONCLUSION: Despite various kinds of therapy, the treatment outcomes for Thai HCC patients remain poor and largely depend on the disease extent and treatment received. Most Thai HCC patients are at an advanced stage at diagnosis. Thai patients who received disease-specific treatment other than intraarterial chemotherapy had a better survival rate than did supportive treatment patients.

Adolescent↗

PubMed2000

Telomerase assay and nested polymerase chain reaction from nasopharyngeal swabs for early noninvasive detection of nasopharyngeal carcinoma.

The main purpose of this study was to analyze sensitivity and specificity of combining nested polymerase chain reaction for detection of Epstein-Barr virus (EBV) genome and telomerase assay for identifying nasopharyngeal carcinoma (NPC). Eighty patients with NPC and 27 healthy control subjects were included in this study; 97. 5% and 94.9% of NPC patients were positive for EBV genome and telomerase activity, respectively. When nasopharyngeal swabs were tested, 95.7% presented the EBV genome and 85.5% were positive for telomerase expression. The sensitivity for counting either positive result of these two techniques was 100%. Among the 27 control subjects, only 6 and 5 cases were positive for EBV DNA and telomerase activity, respectively. This indicated a specificity of 92.6% when both positive results were included. At present, early diagnosis of NPC requires multiple biopsy specimens, especially to identify subclinical cases. Because this study showed a very high sensitivity for detecting NPC from swabs when combining the telomerase assay and nested polymerase chain reaction technique, this noninvasive technique may be a good candidate for screening of subclinical NPC, especially before multiple biopsy specimens are obtained.

Biomarkers, Tumor↗

PubMed2000

Recombinant interferon-alpha 2b and megestrol acetate in patients with advanced renal cell carcinoma.

Fifteen patients with histologically proven metastatic or unresectable renal cell carcinoma were enrolled for a phase II trial of Interferon-alpha 2b (> or = 6 x 10(6) U/m2) plus megestrol acetate (160 mg/day). A response rate of 14.3 per cent was achieved in this study. We observed weight gain (median 3.2 kilogram; range 1.1 to 6.9) in 5 patients, and stable weight in 5 of the 14 patients who completed the protocol. Weight gain occurred regardless of extent of metastasis or response to interferon. Our data suggest a possible role for megestrol acetate in alleviating anorexia and weight loss in patients with renal cell carcinoma undergoing interferon treatment. Further clinical trials are clearly warranted.

Aged↗

PubMed2000

Epstein-Barr virus DNA in serum/plasma as a tumor marker for nasopharyngeal cancer.

Nasopharyngeal cancer (NPC) constitutes a type of carcinoma encountered frequently in Southern China, among Eskimos of the Arctic region, and to a lesser extent in Southeast Asia. Because EBV DNA present in plasma or serum of NPC patients has proven to represent a promising noninvasive tumor marker, the present study was designed to determine the incidence of serum/plasma EBV DNA by nested PCR during various disease management stages. By this method, we could detect EBV DNA in plasma/serum of 98 of 167 NPC patients prior to treatment, compared with 10 of 77 samples derived from healthy blood donors serving as controls, with a similar prevalence observed in plasma versus serum. Investigation of 13 patients subjected to radiotherapy revealed plasma EBV DNA to persist in the plasma of one case, whereas among the remaining patients, it had vanished during the early phase of treatment. Finally, with 52 samples derived from 37 NPC patients during follow-up, we established 100% specificity and 0% false-positive rate for plasma DNA detection by nested PCR. Moreover, we subjected 24 known EBV DNA-positive serum samples to DNase digestion prior to DNA extraction and amplification to differentiate between free and encapsulated viral DNA, which demonstrated complete absence of the human beta-globin genomic DNA in contrast to EBV DNA detectable in 14 samples. In conclusion, applying this noninvasive method, serum/plasma EBV DNA constitutes a reliable tumor marker prior to, during, and after treatment of NPC.

Biomarkers, Tumor↗

PubMed2000

Phase II trial of tropisetron and dexamethasone in the prevention of cisplatin-induced emesis.

Thirty-one patients treated with 58 cycles of cisplatin-based chemotherapy at a dose > 80 mg/m2 were enrolled into the study using tropisetron and dexamethasone in the prevention, of cisplatin-induced emesis. There was 87.9 per cent complete control, 10.3 per cent major control, and 1.7 per cent failure for nausea episode on the first day of cycle. For the vomiting control, there was 96.6 per cent complete control, 3.4 per cent major control, and no failure. After the second day, the percentage of complete control increased gradually for both nausea and vomiting. The complete control for acute nausea and vomiting was 85.7 per cent and 92.9 per cent, respectively. The efficacy for delayed emesis was lower. There was 76.4 per cent complete control for delayed nausea and 85.7 per cent for delayed vomiting. The treatment was well tolerated without any serious adverse events related to tropisetron. Only hiccups was reported in 4 patients and recovered spontaneously at the end of the cycle. Combination of tropisetron and dexamethasone is an effective and safe antiemetic regimen in the prevention of cisplatin-induced emesis.

Adult↗

PubMed2000

Erythropoietin level and hematologic parameters in healthy adults.

Since the major physiological control of erythropoiesis is related to the eryhtropoietin (EPO) level, correlating the EPO level with hematologic parameters in healthy adults, which constitutes an inexpensive and simple routine laboratory report, would be very useful. Two hundred healthy adult blood donors, 100 males and 100 females, aged between 17 and 60 years old were randomly chosen. The EPO reference range was determined by enzyme linked immunosorbent assay (ELISA) using a reagent kit from Research & Development Systems Inc. The hematologic values for reticulocyte and red blood cell parameters were assessed using the Technicon H*3 RTC, an automated blood cell analyzer. The EPO reference range in the studied population was 2.21-20.95 mU/ml. The correlations between the EPO level and hematologic parameters were between -0.302 (p < 0.01) and 0.294 (p < 0.01). The results suggested that there were none or low correlations between the EPO level and hematologic parameters in healthy adults. According to our results, these parameters could not be used to indicate the level of EPO in healthy adults.

Adolescent↗

PubMed1999

Identification of distinct regions of allelic loss on chromosome 13q in nasopharyngeal cancer from paraffin embedded tissues.

Our main purpose was to identify tumor suppressor gene loci on chromosome 13 responsible for nasopharyngeal cancer (NPC) development by analyzing loss of heterozygosity (LOH) and RB protein expression in paraffin embedded tissues. Normal and tumor DNA were extracted from microdissected samples, and their whole genomes were amplified using degenerate oligonucleotide primers. The polymerase chain reaction (PCR) products were analyzed by repeated amplification using primers derived from 16 microsatellite regions spanning the long arm of this chromosome. Among 50 informative cases, LOH was observed in 44 tumors. Thirty-one tumors displayed partial loss and provided an informative basis for detailed deletion mapping. Three minimal regions of loss were delineated; the first flanked by D13S120 and D13S219, the second by D13S126 and D13S119, and the third by D13S137 and 13qter. These 3 regions were linked to BRCA2 on 13q12, RB1 on 13q14, and 13q14.3-ter, respectively. Seven and 4 cases showed LOH either on 13q12 or 13q14, respectively. Nineteen cases showed LOH of both loci separately. One NPC displayed 13q12 and 13q14.3-ter LOH. RB protein expression was detectable in 76% of the cases. Ten out of 15 cases with the allelic losses limited to 13q14 showed RB protein expression. Contrasting that, 6 out of 7 cases devoid of RB protein expressions showed 13q14LOH. In conclusion, 13qLOH, involving 3 tumor suppressor gene loci, appears to be a frequent genetic event occurring during NPC development. However, other tumor suppressor genes besides RB1, may be responsible for the majority of 13q14LOH.

Adult↗

PubMed1999

Tumor angiogenesis.

Tumor angiogenesis is the growth of new blood vessels which is required for tumor growth and progression. Vascularization of the tumor occurs through a series of sequential steps before or during the multistep progression to neoplasia. Several events occur during the formation of new vessels including production of protease enzymes, unregulation of positive regulators of angiogenesis, and down regulation of negative regulators. In addition, tumor associated macrophage also influence angiogenesis by secreting enzymes, enzymes inhibitors and cytokines. Recent knowledge in tumor angiogenesis may have clinical implications in diagnosis and treatment. Quantification of microvessel density in tumor specimen correlates either metastasis or recurrence in many malignancies such as breast cancer and lung cancer. Therefore, assessment of tumor angiogenesis may serve as prognostic factors. Therapeutic applications include the development of new agents with antiangiogenic properties, vascular targeting drugs, antibody-based therapy, and gene therapy. Combination of antiangiogenic therapy with cytotoxic drugs may enhance antitumor activity. Moreover, the role of antiangiogenic therapy in adjuvant setting may provide and alternative approach to better cancer treatment in the near future.

Humans↗

PubMed1999

P53 expression and polysomies of chromosome 9, 17 in head and neck cancer prognosis.

Sixty-nine cases of head and neck squamous cell carcinoma were examined by immunohistochemistry for p53 and chromosome in situ hybridization for chromosome 9 and 17 to determine the relationship between p53 expression and polysomies of chromosome 9 and 17 with the development of a second primary tumor as well as recurrence of primary tumor of head and neck squamous cell carcinoma. We found early expression of p53 in the normal and premaligant lesions adjacent to tumor which was associated with a gradual increase in the fraction of positive nuclei as well as numbers of cancer. We also found statistically significant increments of polysomies of chromosome 9 and 17 in terms of the polysomy index seen through the histologic changes occurring during multistep tumorigenesis. Our results could not demonstrate statistically significant correlation between p53 expression and PI 9 and 17 in tumorigenesis. Interestingly, however, there was a strong correlation between p53 expression and second primary tumor as well as recurrence of primary tumor. The p53 expressed group had a seven fold increased incidence in developing second primary tumor and a two and a half times increased incidence for recurrence of primary tumor, compared to the non-expressed group. We conclude that p53 expression and polysomies of chromosome 9 and 17 have an important role in multistep tumorigenesis in HNSCC. There was no significant correlation between p53 expression and polysomies of chromosome 9 and 17. However, the expression of p53 was statistically significant for association with second primary tumor and recurrence of primary tumor of head and neck squamous cell carcinoma.

Carcinoma, Squamous Cell↗

PubMed1999

Telomerase assay for differentiating between malignancy-related and nonmalignant ascites.

The differential diagnosis between malignancy-related ascites (MRAs) and nonmalignant ascites (NMAs) has remained an essential problem in clinical practice. Our purpose was to determine the diagnostic value of ascitic fluid telomerase activity in discriminating these two categories compared with that of cytological examination. Twenty-five MRAs and 47 NMAs as the control group were enrolled in our study. In the MRA group, telomerase activity was detected in 13 of 16 (81.3%) cases of peritoneal carcinomatosis and in 6 of 9 (66.7%) cases of hepatocellular carcinoma (HCC)-associated ascites. Contrasting that, cytological examination was positive in only 9 of 16 (56.3%) and 1 of 9 (11.1%) cases, respectively. In the NMA group, telomerase-positive ascitic fluid samples were found in 2 of 47 (4.3%) cases, all belonging to subgroups that contained large numbers of lymphocytes in the ascites. In our study, the telomerase activity and cytological examination exhibited a sensitivity of 76% and 40% and a specificity of 95.7% and 100%, respectively. Regarding subgroups of MRAs, the telomerase activity and cytological examination demonstrated a sensitivity of 81.3% and 56.3%, respectively, in peritoneal carcinomatosis and a sensitivity of 66.7% and 11.1%, respectively, in HCC-associated ascites. In conclusion, telomerase activity is a more sensitive marker than cytological examination for differentiating between MRAs and NMAs. It may also serve as a useful indicator for detecting early i.p. metastasis in HCC-associated ascites.

Adult↗

PubMed1998

Loss of heterozygosity on chromosome 14 in nasopharyngeal carcinoma.

The main objective of this study was to determine the precise frequency of chromosome 14q loss of heterozygosity in nasopharyngeal carcinomas and to define its minimal deletion regions. Thirty-nine tumors were selected for PCR-based deletion mapping using 19 microsatellite polymorphic markers spanning the long arm of this chromosome. Loss of heterozygosity for at least one marker was observed in 29 (74.4%) tumors, while 24 of these tumors displayed partial loss and provided an informative basis for detailed deletion mapping. Three minimal regions of loss were delineated, the first defined by markers D14S278 and D14S288, the second being between D14S51 and the telomere. These data confirmed 2 potential tumor-suppressor-gene loci at 14q12-13 and 14q32. Interestingly, the third region of loss was located at the T-cell-receptor delta-chain locus. This may reflect another tumor-suppressor-gene locus at 14q11.2, or may be the consequence of a specific genomic rearrangement of this region. In addition, these allelic losses occurred with high frequency in all tumor grades and stages and in all histological sub-types. These findings suggest that the genetic alteration of chromosome 14 is common and crucial during nasopharyngeal-carcinoma development.

Alleles↗

PubMed1998

Telomerase activity and human papillomavirus in malignant, premalignant and benign cervical lesions.

The purpose of this study was to define a correlation between telomerase activity and human papillomavirus (HPV) in normal control tissue and in benign, premalignant and malignant cervical lesions. Telomerase activity was detectable in 33 out of 34 cases of squamous-cell carcinoma, five out of six cases of microinvasive carcinoma, 8 out of 20 cases and two out of six cases of high- and low-grade squamous intraepithelial lesions (SILs) respectively. The higher frequency of positive telomerase in invasive carcinoma compared with SILs was observed in both HPV-associated and non-associated groups. Whereas 92.6% of HPV-positive and 100% of HPV-negative invasive lesions expressed telomerase, only 50% of HPV-positive and 25% of HPV-negative SILs did. Interestingly, telomerase activity was also detectable in 13 out of 28 cases of benign lesions regardless of the presence of HPV. In conclusion, there may be two roles of telomerase in the cervix. The first one would present in benign lesions; the second is associated with cancer development and activated during the late stage of multistep carcinogenesis in both HPV-positive and -negative groups.

Carcinoma in Situ↗

PubMed1998

Natural history of untreated primary hepatocellular carcinoma: a retrospective study of 157 patients.

Primary hepatocellular carcinoma (HCC) is a common malignancy with a dismal prognosis; new modalities of treatment as alternatives to surgery have been developed for unresectable patients. The authors obtain baseline data for the natural history of HCC so that the efficacy of new treatments may be evaluated. A retrospective study of 157 untreated patients with tissue-proven or serodiagnosed HCC was conducted. Clinical characteristics including laboratory investigation, treatment received, survival from the time of diagnosis, and prognostic factors were evaluated. There were 129 men and 28 women (ratio, 4.6:1). Median age was 50.9 years (range, 14.1-85.3 years). The most common symptoms and signs were weight loss (68.2%), abdominal fullness (62.5%), abdominal pain (51.6%), hepatomegaly (73.7%), ascites (45.2%), and jaundice (40.6%). Eighteen percent had extrahepatic metastases of which the lungs were the most common site. Seventy percent were hepatitis B virus related. Overall median survival was 8.7 weeks after the time of diagnosis. Survivals by stages were: TNM II, 16.6 weeks; TNM III, 7.3 weeks; TNM IVA, 9.7 weeks; TNM IVB, 7.6 weeks; Okuda II, 10.7 weeks; and Okuda III, 7.3 weeks. Multivariate analysis revealed serum total bilirubin and albumin as independent prognostic factors of survival. Common causes of death were upper gastrointestinal hemorrhage (34.1%), cancer-related causes (cachexia, HCC rupture, metastatic disease, 31.8%), and hepatic failure (25.0%). Patients with HCC were diagnosed at late stages of their disease and the advanced nature of the tumor precluded effective therapy. Earlier tumor detection at a time when patients are better candidates for treatment may be aided by an active surveillance program of high risk groups.

Adolescent↗