Biomedical subjects

Fang-Ming Chen

Publications and source records attributed to Fang-Ming Chen.

At least 19 recordsLinked to original sources

PubMed2007

Combination of multiple mRNA markers (PTTG1, Survivin, UbcH10 and TK1) in the diagnosis of Taiwanese patients with breast cancer by membrane array.

OBJECTIVE: Early detection is a prerequisite to the effective reduction of morbidity and mortality from breast cancer. The present study intended to employ a high-throughput membrane array to detect a panel of mRNA markers expressed by circulating tumor cells (CTCs) in the peripheral blood of female patients with breast cancer. METHODS: Peripheral blood was sampled from 92 breast cancer patients and 100 normal persons. CTCs were detected by using a membrane array technique. The markers used included the pituitary tumor transforming gene 1, survivin, UbcH10 and thymidine kinase 1. RESULTS: The results showed that the membrane array could positively detect 5 cancer cells per 1 ml of peripheral blood in breast cancer cell dilution experiments. For the panel of 4 mRNA markers, sensitivity and specificity were elevated up to 86 and 88%, respectively. Furthermore, it was found that the patients' clinicopathological characteristics tumor size (p = 0.006), histologic grade (p = 0.012), lymph node metastasis (p = 0.001) and TNM stage (p = 0.006) significantly correlated with the positive detection rate of the multimarker panel. CONCLUSIONS: These findings demonstrated that our multimarker membrane array method could detect CTCs in the circulation of breast cancer patients with considerably high sensitivity and specificity.

Biomarkers, Tumor↗

PubMed2006

Perforated colonic cancer presenting as intra-abdominal abscess.

BACKGROUND AND AIMS: The various presentations of carcinoma of the colon are well known. Abscess formation occurs in 0.3 to 0.4% and is the second most common complication of perforated lesions. Perforation and penetration of adjacent organs with intra-abdominal abscess formation as the initial presentation is uncommon. MATERIALS AND METHODS: A retrospective analysis was made between January 1998 and December 2003 at the Kaohsiung Medical University Hospital. Six colon cancer patients with intra-abdominal abscess as the initial presentation were enrolled into this study. Among them, two were men and four were women. RESULTS: During the 6-year period, there were 756 patients with colonic carcinoma but only six of those patients (0.79%) presented with abscess formation as the initial finding. The initial pre-operative diagnosis was ruptured colonic diverticulitis with abscess formation in three patients, and the other three patients were as follows: one ruptured appendicitis with abscess, one right subcutaneous inguinal abscess, and one omphalitis with abdominal wall abscess. Subsequent colonoscopy was performed in two patients, and colon cancer was recognized. The most common associated symptoms/signs were palpable abdominal mass, abdominal pain, and anemia. All of them underwent a one-stage surgical procedure, and adjuvant chemotherapy was given. One patient died of peritoneal carcinomatosis and liver metastases 1 year post-operatively. The other five patients are still alive. CONCLUSIONS: It is difficult to make an accurate diagnosis of abscess formation as the first evidence of colonic carcinoma pre-operatively. The one-stage resection of the lesion seems to be an acceptable treatment. For patients with intra-abdominal abscess, clinicians should be aware of this differential because it is easily ignored pre-operatively.

Abdominal Abscess↗

PubMed2006

Randomized controlled trial of LigaSure with submucosal dissection versus Ferguson hemorrhoidectomy for prolapsed hemorrhoids.

INTRODUCTION: The aim of this study was to compare the outcomes between the LigaSure vessel sealing system and the conventional closed Ferguson hemorrhoidectomy procedure performed by diathermy. METHODS: A series of 84 patients with grades III and IV hemorrhoids were randomized into two groups: (1) LigaSure hemorrhoidectomy with submucosal dissection (42 patients) and (2) Ferguson hemorrhoidectomy (42 patients). The patient demographics, operative details, parenteral analgesic requirement, postoperative pain score (assessed by an independent assessor), operating time, intraoperative blood loss, hospital stay, early and delayed complications, and time off from work or normal activity were recorded. The patients were regularly followed up at 1, 2, 4, 6, and 8 weeks after surgery. RESULTS: There were no statistically significant differences between the two groups in terms of age, gender, duration of symptoms, grade of the hemorrhoid(s), or number of hemorrhoids resected. The mean operating time for LigaSure hemorrhoidectomy with submucosal dissection was significantly shorter than that for the Ferguson hemorrhoidectomy (11.3 +/- 0.4 vs. 34.2 +/- 0.7 minutes; P < 0.0001). Patients treated with the LigaSure method had significantly less blood loss (P < 0.0001), a better pain score (P < 0.0001), less parenteral analgesic requirement (P < 0.0001), shorter hospital stay (P < 0.0001), and less time off from work or normal activity (P < 0.0001). There was no difference in the early and delayed postoperative complications between the two groups. CONCLUSIONS: LigaSure hemorrhoidectomy with submucosal dissection is a safe, effective procedure for grade III and IV hemorrhoids. Patients derive greater short-term benefits: reduced intraoperative blood loss, operating time, and postoperative pain as well as earlier resumption of work or normal activity. Long-term follow-up with a larger number of patients is required to confirm the long-term results of this procedure.

Adult↗

PubMed2006

Clinical characteristics of patients with sporadic colorectal cancer and primary cancers of other organs.

Most cancer patients often neglect the possibility of secondary cancer. Colorectal cancer (CRC) is the third leading cause of cancer death in Taiwan. It is important to be aware of the clinical characteristics of double cancer in CRC patients for early diagnosis and treatment. We retrospectively analyzed 1,031 CRC patients who underwent surgical treatment at the Department of Surgery of Kaohsiung Medical University Hospital between January 1998 and December 2004. Among these patients, CRC was accompanied by cancer of other organs in 17 patients (1.65%), either synchronously or metachronously. Therefore, we describe our experience regarding the location of CRC, the clinical symptoms and signs of these patients, the TNM stage, histology, phase, association with other malignancies, interval between cancers and clinical outcomes. Of the 17 patients in whom CRC was accompanied by primary cancer of other organs, there were four synchronous and 13 metachronous multiple cancer patients. Our patient group comprised six men and 11 women with ages ranging from 47 to 88 years (median age, 66 years). The most common location of CRC was the sigmoid colon. Six gastric cancers (35.2%) and six breast cancers (35.2%) were associated with primary CRC. The remaining six second primary cancers were one lung cancer, one thyroid cancer, one cervical cancer, one ovarian cancer, one skin cancer, and one urinary bladder cancer. Of the 13 metachronous multiple cancer patients, eight patients developed subsequent CRC after primary cancers of other organs, whereas two patients developed a subsequent second primary cancer after CRC. The intervals between the development of metachronous multiple cancers ranged from 2 to 19 years. In this retrospective analysis, breast and gastric cancer patients were at increased risk of developing subsequent secondary CRC. Careful attention should always be paid to the possibility of secondary CRC in treating these cancer patients. Cancer patients with hematochezia or gastrointestinal symptoms/signs should be evaluated for the possibility of second primary CRC during their regular follow-up.

Aged↗

PubMed2006

Sarco/endoplasmic reticulum calcium-ATPase 2 expression as a tumor marker in colorectal cancer.

Maintaining a high calcium concentration in the endoplasmic reticulum through the action of sarco/endoplasmic reticulum calcium-ATPases (SERCAs) is crucial in many cell functions involved in intracellular signal transduction, control of proliferation, programmed cell death, or the synthesis of mature proteins. Recent studies have found that many SERCAs have altered expression patterns in various malignancies. The purpose of the current study was to quantify the expression of SERCA2 in colorectal cancer (CRC) tissues and the corresponding noncancerous tissues, and to statistically analyze whether the SERCA2 expression levels correlate with the clinico-pathologic features and prognosis of CRC patients. Paired colorectal tissue samples from cancerous and the corresponding noncancerous tissues were obtained from 50 patients who underwent surgical resection. Semiquantitative measurements of SERCA2 messenger RNA (mRNA) expression were done using the multiplex reverse transcriptase-polymerase chain reaction. CRC tissues were analyzed through immunohistochemistry for the SERCA2 protein. SERCA2 mRNA overexpression in cancerous tissues compared with normal counterparts was observed in 45 of 50 (90%) patients. The mean expression level of SERCA2 mRNA in cancerous tissues was significantly higher than that in noncancerous tissues (P = 0.01). Increased SERCA2 protein expression was significantly correlated with serosal invasion (P = 0.012), lymph node metastasis (P = 0.009), and advanced tumor stage (P = 0.004). Furthermore, patients with high SERCA2 expression had a significantly poorer overall survival rate than patients with low SERCA2 (P = 0.032). Multivariate analyses indicated that tumor stage (P = 0.015) and SERCA2 expression were independently correlated with overall survival (P = 0.018). The result of this study indicated that SERCA2 may be a molecular determinant in the development and progression of CRC. The molecular mechanisms underlying the SERCA-dependent calcium accumulation and CRC tumorigenesis are worthy of further investigations.

Adenocarcinoma↗

PubMed2006

Endothelin-1, inducible nitric oxide synthase and macrophage inflammatory protein-1alpha in the pathogenesis of stress ulcer in neurotraumatic patients.

BACKGROUND: To prospectively identify histologically and endoscopically the effect of omeprazole on the expression of endothelin-1 (ET-1), inducible nitric oxide synthase (iNOS) and macrophage inflammatory protein-1alpha (MIP-1alpha) in the gastric mucosa of neurosurgical patients with stress ulcer. METHODS: Twenty-five patients with severe acute intracranial lesions caused by trauma were enrolled in this study. A 40 mg intravenous bolus of omeprazole (OME) was given daily for 7 days. The intragastric pH was continuously recorded for 24 hours on day 1 and 8. Endoscopic evaluation of the gastric corpus, antrum, and duodenal bulb was performed in the ICU, within 24 hours after brain injury, and at follow-up on the 7th day after admission. Paired biopsies were obtained for histologic examinations and immunohistochemical analysis was performed using a LSAB method for MIP-1alpha, ET-1, and iNOS. RESULTS: There were 72% and 70% of gastroduodenal mucosal lesions at the initial and follow-up endoscopies, respectively. However, the severity of mucosal lesions showed significant improvement in most patients at follow-up (p < 0.05). Mean percentages of time intragastric pH were greater than or equal to 4.0 were 20 +/- 11% and 70 +/- 17% on day 1 and 8, respectively (p < 0.05). The incidences of ET-1, iNOS and MIP-1alpha expression were not significantly different between the patients before and after OME prophylaxis. CONCLUSIONS: Prophylactic OME is effective in reducing the severity of stress ulcerations in severe neurotraumatic patients. High incidence of tissue ET-1 expression combined with increased activity of iNOS and MIP-1alpha may be responsible for the gastric mucosal injury. We also show that OME fails to counter the enhancement in the mucosal expression of ET-1, iNOS, and MIP-1alpha caused by severe brain damage.

Adult↗

PubMed2005

High frequency of somatic missense mutation of BRCA2 in female breast cancer from Taiwan.

Somatic mutation of BRCA2 has been thought to be rare in breast cancers, though common allelic deletions in the BRCA2 locus (13q12-q13) imply an important role of somatic mutation in these tumors. Reasons of the reported rare incidence could be related to very few studies focusing on the mutational analysis of BRCA2 in sporadic tumors. The mutational status of the BRCA2 gene in exon11, the largest exon harboring the RAD51 interacting BRC domains which are critical for BRCA2 function, was screened by polymerase chain reaction/single strand conformation polymorphism (PCR-SSCP) analysis followed by direct sequencing. Tumor and paired normal tissue sample from 175 patients unselected for family history or age were taken after mastectomy for breast cancer and evaluated. There were 20 mutations of BRCA2 gene in exon 11 in 15 cases (15/175, 8.6%). Most mutations we identified were point mutation (19/20, 95%), except for one nucleotide insertion. Furthermore, among these mutations, missense mutations comprised 80% (16/20) of the BRCA2 mutations. All mutations we found were novel mutation after searched in the BIC database. There were three recurrent mutations at codon 1904; and two recurrent mutations at 1907, 1936, 1937 and 1968, respectively. The mutations were associated with ductal carcinoma in situ (P=0.038) and borderline with low histological grade (P=0.072). Besides, there were three cases possessing multiple mutations in the region we studied and one of them demonstrated aggressive lymph node metastasis. These findings implicated that somatic mutations of BRCA2 genes may play a significant role in the pathogenesis of breast carcinoma in Taiwan. In addition, those events were associated with some early clinicopathological features.

Adult↗

PubMed2005

Efficacy of medium-chain triglycerides compared with long-chain triglycerides in total parenteral nutrition in patients with digestive tract cancer undergoing surgery.

The objectives of this prospective, randomized study were to evaluate the efficacy and tolerability of the short-term use of medium-chain triglyceride/long-chain triglyceride (MCT/LCT) fat emulsions, and to compare the hematologic and biochemical effects of MCT/LCT fat emulsions with LCT fat emulsions in gastrointestinal (GI) tract cancer patients following surgery. Thirty patients with GI tract cancer requiring total parenteral nutrition (TPN) were equally randomized to receive MCT/LCT or LCT emulsions for 7 days. After 7 days, no sign of complications directly related to administration of fat emulsions was observed and there were no marked differences in anthropometry, length of hospital stay, and surgical complication rates between the two groups. However, MCT/LCT significantly improved plasma prealbumin concentration (p = 0.005). Changes in complements C3 and C4, total lymphocyte count, and immunoglobulins after TPN were not significantly different between the groups. Serum triglyceride and cholesterol levels remained constant. The serum insulin level in the MCT/LCT group was higher than in the LCT group (p = 0.048). Our data revealed that MCT/LCT fat emulsions significantly enhanced nutritional status in patients with GI tract cancer, indicated by higher prealbumin levels, which might be partially due to the higher circulating insulin levels in the MCT/LCT group.

Aged↗

PubMed2005

Abdominopelvic perivascular epithelioid cell tumor with overt malignancy: a case report.

Perivascular epithelioid cell tumor (PEComa) is a group of rare tumors composed of epithelioid cells with characteristic perivascular distribution and co-expression of the melanogenic marker HMB-45 and muscular markers. There are no documented parameters referring to the biologic behavior of PEComa. We report an abdominopelvic PEComa with overt malignancy in a 16-year-old girl. Histologically, the tumor showed the typical morphophenotypic characteristics of PEComa. Though the cytologic appearance of the tumor cells was relatively bland, the extensive necrosis, presence of lymph node metastases, and surrounding tissue invasion were all indicative of malignancy. Relapse of the tumor with multiple lymphadenopathy shortly after debulking surgery for the primary lesion, and postoperative adjuvant chemotherapy, further denoted its aggressive behavior.

Abdominal Neoplasms↗

PubMed2005

APC, K-ras, and p53 gene mutations in colorectal cancer patients: correlation to clinicopathologic features and postoperative surveillance.

Current researches have proposed a genetic model for colorectal cancer (CRC), in which the sequential accumulation of mutations in specific cancer-related genes, including adenomatous polyposis coli (APC), K-ras, and p53, drives the transition from normal epithelium through increasing adenomatous dysplasia to colorectal cancer. To identify patients with an increased risk of tumor recurrence or metastasis and evaluate the prognostic values of APC, K-ras, and p53 gene mutations, we investigated the frequency of these three mutated genes in tumors and sera of CRC patients. APC, K-ras, and p53 gene mutations in primary tumor tissues and their paired preoperative serum samples of 118 CRC patients were detected by using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, followed by direct DNA sequencing of the PCR-amplified genomic DNA. Subsequently, serum molecular markers were analyzed for their correlation with patients' clinicopathologic features and presence of postoperative recurrence/metastasis. We did not observe any significant difference in the association of APC or K-ras or p53 gene mutations in primary tumors with patients' demographic data (all were P > 0.05). In contrast, both serum APC and p53 molecular markers were closely correlated with lymph node metastasis and TNM stage (both P < 0.05). Moreover, the serum overall molecular markers (at least one of the three markers) were prominently associated with depth of tumor invasion (P = 0.033), lymph node metastasis (P < 0.001), and TNM stage (P < 0.001). In addition, a significantly higher postoperative metastasis/recurrence rate in patients positive for overall molecular markers compared to those negative for these molecular markers were also demonstrated (P < 0.001). APC and K-ras molecular markers were more frequently observed in patients with locoregional metastasis (both P < 0.05), while p53 molecular marker was usually detected in the cases of peritoneal metastasis (P = 0.004). Our findings suggest that serum molecular markers are potentially useful in the determination of colorectal cancer patients harboring gene mutations at high risk of metastasis. Serial analysis is warranted in order to assess their long-term prognostic significance and the therapeutic implications.

Biomarkers, Tumor↗

PubMed2005

Analysis of progressively overexpressed genes in tumorigenesis of colorectal cancers using cDNA microarray.

The identification of differentially expressed genes has important implications in understanding the biology of colorectal tumorigenesis and progression, as well as developing new diagnostic and therapeutic strategies. In this study, cDNA microarray technology was used to identify colorectal tumor-related functional genes, which are overexpressed continuously from colorectal adenoma to adenocarcinoma. A set of 23 genes with progressive overexpression in the development of colorectal cancer (CRC) was identified by cDNA microarray, then analyzed by sequencing and Northern blot analysis. Validation of our array results was simultaneously performed by exploring the SAGEmap database. Furthermore, the gradually over-expressed genes from adenoma to adenocarcinoma were validated by Northern blot analysis with additional samples from three patients with synchronous colorectal adenocarcinoma and adenoma and four patients with CRC. Of these 23 genes, one was a function-unknown gene, designated as Homo sapiens chromosome 21q22.1 anonymous mRNA sequence (Genbank accession no. AF003738), and 22 were function-known genes. Searching through the Gene Ontology Browser at the Cancer Genome Analysis Project website revealed that the biological roles of these 22 function-known genes are involved in cell motility, cell adhesion, chemokine activity, signal transduction, cytoskeleton organization, proteolysis, apoptosis, and cell proliferation. The genes identified in the present study offer valuable information on colorectal carcinogenesis and metastasis, and represent a potential source of novel targets for new strategies for CRC diagnosis and therapy.

Blotting, Northern↗

PubMed2005

Preoperative evaluation of endoscopic ultrasonography and portography in selecting devascularization surgery for esophagogastric varices.

This study assesses the role of endoscopic ultrasonography (EUS) and portography in selection of mode of devascularization surgery for esophagogastric varices (EGV) in patients with portal hypertension and reports our experience in the treatment of EGV with modified devascularization surgery. Forty-two cirrhotic patients with EGV were treated with devascularization surgery for variceal hemorrhage. Preoperatively, percutaneous transhepatic portography (PTP) and EUS were used as the guiding mode for therapy of EGV. In addition to devascularization and splenectomy, esophageal transection (ET) was performed in 26 patients with upward-flow varices (UFV), whereas 16 patients with downward-flow varices (DFV) underwent proximal gastrectomy instead of ET. In both UFV and DFV groups, grade II of intramural varices and extramural collaterals were most commonly observed on EUS imaging. There was no significant difference of EUS grading between these two groups (P > 0.05). The incidence of postoperative complications, mortality, and recurrent varices were not significantly different between these two groups. The overall 5-year survival rate for UFV group was 69.2 per cent, whereas that for the DFV group was 68.7 per cent (P > 0.05). Our study shows that devascularization surgery is highly effective for the prevention of recurrent bleeding from EGV, and it provides an alternative treatment modality. Combined PTP and EUS are very helpful in determining adequate modalities of devascularization surgery.

Adult↗

PubMed2004

High frequency of frameshift mutation on p53 gene in Taiwanese with non small cell lung cancer.

Extensive researches have found that the mutation of p53 tumor suppressor gene is the most frequent event in many human cancers and associated with a poor clinical outcome in lung cancer patients. Because the p53 molecular mutation involved in tumorigenesis of patients with lung cancer in Taiwan remains poorly defined, the aim of this study was to assess the p53 mutation spectrum and possible etiological factors of Taiwan's patients with Non-Small Cell Lung Cancer (NSCLC). Cancer specimens were obtained surgically from 61 patients with pathologically proven NSCLC. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing were used to study p53 mutations in exon 4-8. We also performed immunohistochemistry (IHC) to detect p53 protein expression. Our results provided that 34 mutations of p53 gene were found in 27 cases with a mutation rate of 44% (27/61). There were six cases having more than two p53 mutations. Among the 34 mutations, 19 were point mutations (56%, 19/34) consisted of a majority of missense mutations including transversion (13/19, 68%) and transitions (6/19, 32%) with four cases (4/6, 67%) occurring in the CpG sequence. One of the most important finding in our study was the high frequency of frameshift (44%, 15/34) which included 11 insertions and 4 deletions of p53 in NSCLC in Taiwan. Surprisingly, our results disclosed distinct novel mutations at codon 181, 185, 208 (Exon 5-6) of p53. Especially, 4 cases with mutation at codon181 and codon 185 seemed to have more advanced clinical outcome with survival time less than 6 months. In addition, there were two recurring mutations at codon 168 and three at condon193. The different mutation spectrum in our series, including a high frequency of frameshift mutations and distinctly novel hot spots suggested the heterogenous entity of exogenous mutagens in NSCLC in Taiwan.

Aged↗

PubMed2004

Gastric cancer cell detection in peritoneal lavage: RT-PCR for carcinoembryonic antigen transcripts versus the combined cytology with peritoneal carcinoembryonic antigen levels.

Free cancer cells exfoliated from the serosal surfaces of primary cancers are considered to be responsible for peritoneal dissemination, which are both the most frequent pattern of treatment failure and the most important cause of death in gastric cancer patients. Detection of free cancer cells in the peritoneal cavity at the time of surgery, therefore, is thought to be of great value in predicting peritoneal recurrence and accordingly the prognosis of gastric cancer patients. This study was designed to determine whether free cancer cells in peritoneal lavage fluid from gastric cancer patients could be identified by a reverse-transcriptase polymerase chain reaction (RT-PCR) method specific to carcinoembryonic antigen (CEA) mRNA. Simultaneously, the results from conventional cytological examination were evaluated and the levels of CEA in peritoneal lavage were determined. Of the 40 gastric cancer patients enrolling in this investigation, 11 (27.5%) were positive for CEA mRNA in their peritoneal lavage, whereas only 6 (15%) and 8 (20%) were shown to be positive by cytological examination and peritoneal CEA (pCEA) assay, respectively. Furthermore, RT-PCR positive for CEA mRNA was correlated with the depth of tumor invasion (P<0.001), lymph node metastases (P=0.004), the TNM stage (P<0.001) and peritoneal recurrence (P<0.001). The technique of RT-PCR was more sensitive than conventional cytological examination and pCEA levels in the detection of peritoneal free cancer cells as well as in the prediction of peritoneal recurrence. In addition, CEA RT-PCR had a high concordance rate (82.5%) with the combination of cytology with pCEA levels. These observations suggest that it is feasible to identify free cancer cells in peritoneal lavage by using a CEA mRNA-specific RT-PCR method, and this assay can be a promising diagnostic modality for evaluating the risk of peritoneal dissemination in gastric cancer patients following operations.

Carcinoembryonic Antigen↗

PubMed2004

Molecular detection of APC, K- ras, and p53 mutations in the serum of colorectal cancer patients as circulating biomarkers.

Early detection of tumor DNA in serum/plasma prior to the development of recurrence or metastases could help improve the outcome of patients with colorectal cancer (CRC) after tumor resection. Recent advances in the detection of tumor DNA in the serum/plasma has opened up numerous new areas for investigation and new possibilities for molecular diagnosis. APC and K- ras mutations are considered to be early-stage developments of CRCs, whereas p53 mutations are thought to be relatively late events in the tumorigenesis of CRCs. The aim of this study was to search for the presence of genetic mutations in the DNA extracted from the serum of CRC patients and healthy subjects. We simultaneously evaluate the significance of APC, K- ras, and p53 gene mutations in cancer tissues and their paired serum samples of 104 CRC patients by polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SSCP) followed by direct sequencing. Additionally, analysis was carried out to detect the serum carcinoembryonic antigen (CEA) levels in CRC patients. Overall, we found at least one of the gene mutations in tumor tissues from 75% (78/104) of the CRC patients. Comparison of the three molecular markers showed that the detection rates in the serum were 30.4%, 34.0%, and 34.2% for APC, K- ras, and p53 genes, respectively. Of these patients, 46.2% (36/78) were identified as having positive serum results, whereas all healthy controls remained negative. The overall positive tumor DNA detection rates in the serum were 0% (0/7) for Dukes' A classification, 22.4% (11/49) for Dukes' B, 48.7% (19/39) for Dukes' C, and 66.7% (6/9) for Dukes' D. The detection rate increased as the tumor stage progressed ( p = 0.012). Concurrently, a significant difference was observed between lymph node metastases and positive serum tumor DNA detection ( p < 0.001). A significantly higher postoperative metastasis/recurrence rate in patients harboring gene mutations with serum tumor DNA than those without serum tumor DNA was also demonstrated ( p < 0.001). However, no significant correlation between the postoperative metastasis/recurrence and serum CEA levels was observed ( p = 0.247). These data suggest that the identification of circulating tumor DNA using the molecular detection of APC, K- ras, and p53 gene mutations is a potential tool for early detection of postoperative recurrence/metastases. Moreover, these genes may be potential molecular markers of poor clinical outcome in CRC patients.

Aged↗

PubMed2004

High frequency of G/C transversion on p53 gene alterations in breast cancers from Taiwan.

p53 gene mutation is a very frequent event in many human cancers and is associated with a poor clinical outcome in breast cancer patients. Analysis of p53 gene mutations can also provide clues to the etiology of tumor formation. The present study was conducted to investigate the p53 mutations in patients with breast cancer from Taiwan. Tumor samples from 119 patients undergoing mastectomy for breast cancer were evaluated. The mutational status of the p53 gene (exons 5-8) was screened by polymerase chain reaction-single strand conformation polymorphism analysis followed by direct sequencing. Of all 119 cases of breast carcinoma, 26 mutations of the p53 gene were found in 22 cases (18.5%). Among these mutations, 78% (20/26) were point mutations with the majority of those being missense mutations (75%, 15 of 20 mutations) and the other 22% (6/26) were frameshift mutations. No significant correlation between p53 mutations and clinicopathological features was found, including HER2 status. Moreover, our results disclosed distinct mutation spectra in excess transversions to transitions (15/21, 71.4% vs. 6/21, 28.6%) with GC to CG dominant (6/15, 40%). Mutation hot spots we identified at codons 167, 185, 186, 210, 265 and 295 have rarely been documented in the literature. These findings showed that p53 gene mutation might contribute to the pathogenesis of breast carcinoma. Furthermore, the different mutation spectrum with high transversions in G:C to C:G may imply that the exogenous mutagens outweigh the endogenous processes in breast cancer in patients in Taiwan.

Breast Neoplasms↗

PubMed2004

Alterations of APC, c-met, and p53 genes in tumor tissue and serum of patients with gastric cancers.

BACKGROUND: Gastric cancer is one of the most significant causes of cancer-related death worldwide. A genetic model consisting of sequential accumulations of alterations in specific genes for gastric cancer has been proposed. MATERIALS AND METHODS: The significance of adenomatous polyposis coli (APC) and p53 gene mutations in cancer tissues and their paired serum of 34 gastric cancer patients was investigated using polymerase chain reaction single-strand conformation polymorphism analysis (PCR-SSCP), followed by direct sequencing. c-met mRNA expression was evaluated by reverse-transcription PCR (RT-PCR). Additionally, analyses were carried out to detect the serum carcinoembryonic antigen (CEA) levels, and their correlation to these three molecular markers. Finally, serum molecular markers and their correlation to the presence of postoperative recurrence/metastasis were analyzed. RESULTS: Of all, 32.4% of patients presented mutations in APC and p53, respectively, and 58.8% presented the overexpression in c-met, overall, at least one of these genetic alterations in 79.4% of tumor tissues. Comparison of three molecular markers showed that the individual detection rate in the serum of patients with tumors harboring the same abnormalities was 18.2, 70.0, and 36.4% for APC, c-met, and p53 genes, respectively. In general, 59.3% of serum from cancerous tissues with gene alterations was demonstrated as positive, whereas all healthy volunteers' sera remained negative. Regarding gene alterations in tumor tissues, c-met overexpression was significantly related to the tumor size (P = 0.017), depth of tumor invasion (P = 0.007), lymph-node metastasis (P < 0.001), and TNM stage (P = 0.001). In the serum, c-met overexpression was closely associated with lymph-node metastasis (P = 0.008) and TNM stage (P = 0.016). The overall positive tumor gene detection rate in the serum was prominently correlated to the serum CEA levels (P = 0.038). In addition, a significantly higher postoperative metastasis/recurrence rate in patients harboring gene mutations with serum molecular markers than those without serum molecular markers was also demonstrated (P = 0.014). CONCLUSIONS: Our findings suggest that serum molecular markers can be detected in a substantial proportion of gastric cancer patients, and these may offer an auxiliary approach in the noninvasive detection and prognosis of gastric cancer.

Carcinoembryonic Antigen↗

PubMed2003

Effect of spontaneous portosystemic shunts on hemorrhage from esophagogastric varices.

The role of a massive spontaneous portosystemic shunt (MSPSS) in cirrhotic patients with portal hypertension remains unclear. The aim of this study was to investigate clinical outcomes and portal hemodynamic changes following ligation of the MSPSS during devascularization surgery. Portography and gastroendoscopy were performed before and after surgery for hemodynamic and follow-up studies. Three types of MSPSS were demonstrated portographically: 22 portoumbilical shunts, 18 splenorenal shunts, and 2 inferior mesenteric-caval shunts. A total of 40 MSPSS patients with esophagogastric variceal (EGV) bleeding underwent surgery: 26 had ligation of the MSPSS, and the remaining 14 served as the nonligation group. Neither the preoperative mean portal pressure (MPP) nor the postoperative MPP were significantly different between the ligation and nonligation groups (p>0.1), and there was no significant difference regarding surgical mortality, recurrent varices, or cumulative survival rate for the two groups in the follow-up study. However, postoperative portography demonstrated persistent drainage of portal flow and decreased intrahepatic portal perfusion in the nonligation patients. Clinical signs of hepatic encephalopathy subsided after ligation of the MSPSS in three patients. Therefore ligation of the MSPSS, which may be responsible for the development of encephalopathy, is recommended during devascularization surgery for EGV in cirrhotic patients.

Adult↗