Biomedical subjects

R L Hong

Publications and source records attributed to R L Hong.

33 records · Page 2Linked to original sources

PubMed1998

Overexpression of p53 predicts shorter survival in diffuse type gastric cancer.

BACKGROUND: It has been suggested that p53 plays an important part in gastric carcinogenesis but the data remain inconclusive. METHODS: Alteration of the tumour suppressor gene p53 was prospectively investigated by immunohistochemistry in 168 primary gastric cancers. RESULTS: Positive staining, indicative of gene mutations, was detected in 34 tumours (20.2 per cent). No correlation was observed between expression of p53 and various clinicopathological factors, including age, sex, tumour site, gross type, tumour size, depth of invasion, lymph node metastases, distant metastases, and tumour node metastasis stage. However, p53 overexpression was different between intestinal and diffuse type gastric cancer. Survival analysis revealed a significant survival disadvantage of p53 expression in diffuse type gastric cancer (P=0.039) but not in the intestinal type. Multivariate analysis of all 168 patients revealed that independent predictors of recurrent disease included age, invasion depth and nodal involvement but not p53 expression. CONCLUSION: The presence of p53 overexpression may identify a subset of more aggressive tumours with a poor prognosis in diffuse type gastric cancer.

Adenocarcinoma↗

PubMed1998

Relation between histological intensity of transforming growth factor-beta isoforms in human osteosarcoma and the rate of lung metastasis.

Even though adjuvant chemotherapy has improved the 5-year survival rate of osteosarcoma patients, a significant percentage of patients eventually die from lung metastasis. Since transforming growth faCtor-beta (TGF-beta) has been demonstrated to be related to the tumor progression, we investigated the clinical implications of the presence of TGF-beta isoforms in 16 human osteosarcoma tissue. There were 10 males and 6 females with a mean age of 20.8 years of age (range, 8 to 57 years). Biopsied specimen before chemotherapy was fixed in 10% formalin, demineralized and followed by paraffin embedding. The locations of tumor included femur (10), tibia (3), humerus (1), fibula (1), and ilium (1). Histologic subtypes included osteoblastic (11), chondroblastic (2), and fibroblastic (3). All patients were followed for a minimum of 1 year (range 12 to 44 months) or to the development of lung metastasis. Five patients (31.3%) developed subsequent lung metastasis during the follow up. We used immunohistochemistry technique to investigate the presence of the TGF-beta isoforms in osteosarcoma tissue and its relationship to the subsequent pulmonary metastasis. The results showed the presence of one or more TGF-beta isoforms in tumor cells in osteosarcoma tissues (13 of 16, 81.3%) in all of the subtypes. However, minimal presence of TGF-beta isoforms was shown in the tumor bone matrix. The expression of TGF-beta1 or TGF-beta3 isoforms was associated with a higher rate of subsequent lung metastasis (p < 0.05, chi-square test). Further research is warranted to determine the utility of routine TGF-beta analysis in the clinical practice.

Adolescent↗

PubMed1997

MVP (mitomycin-C, vinblastine, cisplatin) salvage chemotherapy for relapsed and refractory metastatic breast cancer.

Salvage chemotherapy for relapsed and refractory metastatic breast cancer is a challenging issue for oncologists. At our institution, the combination of mitomycin-C, vinblastine and cisplatin (MVP) is used for treatment. The records of 19 consecutive patients with refractory metastatic breast cancer treated with MVP between April 1992 and October 1995 were reviewed. The regimen consisted of mitomycin-C 6 mg/m2, vinblastine 6 mg/m2 and cisplatin 60 mg/m2, repeated every 3 to 4 weeks. The median age of patients was 49 years (range, 35-71 yr). All patients had clinically measurable or evaluable disease and a Karnofsky's performance status greater than or equal to 50%. The median number of prior chemotherapy regimens was two (range, 1-4). Eighteen (94.7%) patients had previously received an anthracycline/anthracenedione-containing regimen, and seven (36.9%) had progression of disease during these therapies. Sixteen patients had two or more sites of metastasis and 17 patients had visceral disease. The median duration of follow-up was 26 months. A mean of 3.5 courses (range, 1-7) was administered. One patient was lost to follow-up after one course of treatment. Of the remaining 18 patients, two complete and five partial responses were observed, for a total response rate of 37% (range, 17-61%, 95% CI). One of the partial responders had disease progression during anthracycline treatment. Treatment-related toxicities were relatively well tolerated. There were no treatment-related deaths. The median duration of response was 3 months (range, 2-11 mo). The median overall survival was 7 months (range, 1-32 mo). Our data suggest that the MVP regimen is an effective palliative treatment for patients with refractory metastatic breast cancer.

Adult↗

PubMed1996

Experience of radiotherapy in lethal midline granuloma with special emphasis on centrofacial T-cell lymphoma: a retrospective analysis covering a 34-year period.

Lethal midline granuloma (LMG) is characterized by progressive ulceration and destruction of the midfacial tissue. It occurs more frequently in Oriental than in Western populations. Because of the progress in clinical pathology and immunohistochemistry, most cases have been proven to be malignant lymphomas, especially of T-cell lineage. We describe 92 cases of lethal midline granuloma or centrofacial malignant lymphoma in the period 1959-1993. All received complete courses of radiotherapy. Twenty of them also received combination chemotherapy. Thirty-six cases had specimens available for immunohistochemical study; 25 (69%) of these had a T-cell phenotype, and 6 (17%) were of B-cell lineage. The dose to the nasal region was in the range of 3000-7500 cGy in 11-58 days, and to the neck 3000-6400 cGy in 11-48 days. The overall survival rate for the LMGs was 59.5% at 5 years and 56.2% at 10 years (Kaplan-Meier). Combined chemotherapy seemed not to improve the overall survival in this study (p = 0.63), but the patient number was too small to make a firm conclusion. Based on the results of this study, we recommend a dose of 4500-5000 cGy to the midfacial region, since a higher dosage did not improve the treatment results (p = 0.88). Irradiation has a definite role in good locoregional control of this disease. The recent clarification of the disease nature and the recognition of the background clinicopathological features should provide valuable information for future patient management and prospective studies.

Adolescent↗

PubMed1995

Correlation of expression of CD44 isoforms and E-cadherin with differentiation in human urothelial cell lines and transitional cell carcinoma.

Using immunostaining, immunoblot, reverse-transcriptase polymerase chain reaction and Southern blot, we found that expressions of CD44 isoforms and E-cadherin were very closely linked and were correlated with the differentiation status in human urothelial cell lines and clinical specimens of transitional cell carcinoma. Normal urothelium, well to moderately differentiated cell lines and surgical samples expressed E-cadherin and large CD44 isoforms containing exon v6, which was pivotal in metastasis of rat pancreatic cell line model. Poorly differentiated cell lines and surgical samples, were E-cadherin-negative and expressed primarily standard form CD44, which did not contain exon v6. We concluded that CD44v6 isoforms and E-cadherin were both down-regulated during the carcinogenesis of urothelium. The large exon v6 containing CD44 isoforms were readily detected in normal urothelium, therefore, were not likely linked to cancer metastasis. E-cadherin and CD44v6 may be used as differentiation markers for human urothelial tumors. Immunohistochemical study solely with antibody against epitopes encoded by exon v6 alone is not informative enough as other alternatively spliced exons may change the function of CD44v6 isoforms.

Animals↗

PubMed1995

Clinicopathologic characteristics of Helicobacter pyloric seropositive gastric adenocarcinomas.

To compare and characterize retrospectively the clinicopathologic features of gastric cancers with and without previous Helicobacter pylori infection, we determined the preoperative seropositivity of H. pylori in 151 patients who had undergone gastric resection for primary gastric adenocarcinoma between 1988 and 1993. The overall seroprevalence of H. pylori was 60.9%. H. pylori-positive gastric cancers were frequently associated (p<0.05) with macroscopic localized types (Borrmann I and II) in which negative cancer associated with infiltrative types (Borrmann III and IV) and cancer invasion of the duodenum. Multivariate analysis showed that H. pylori seropositivity was not an independent prognostic factor. Pathologic tumor-node-metastases (TNM) stage remained the only prognostic indicator. Our study suggests that H. pylori has a significant impact on the clinically relevant tumor biology of gastric cancer. Investigation along this line is warranted.

Adenocarcinoma↗

PubMed1995

Expressions of E-cadherin and exon v6-containing isoforms of CD44 and their prognostic values in human transitional cell carcinoma.

Cell surface adhesion molecules, E-cadherin and exon v6 containing CD44 isoforms (CD44v6), were readily found in well-to-moderately differentiated urothelial cell lines but were down-regulated in poorly differentiated cell lines. One hundred and fifteen tumors of transitional cell carcinoma (TCC) were examined with E-cadherin and CD44v6 specific antibodies. Sixty-five (56.5%) tumors exhibited a preserved type while 50 (43.5%) showed a reduced type for CD44v6. Sixty-seven (58.3%) tumors were classified as the preserved type, and 48 (41.7%) were classified as the reduced type for E-cadherin. The staining pattern of E-cadherin was the same as that of CD44v6 in 87.0% (100 of 115) of tumors. The frequency of the reduced type was higher in poorly differentiated carcinomas (32 of 52 for CD44v6, p = 0.001; 27 of 52 for E-cadherin, p = 0.112) and tumors with an invasive growth pattern (22 of 27 for CD44v6, p < 0.001; 20 of 27 for E-cadherin, p < 0.001) than it was in well-differentiated carcinomas and tumors with expansile growth. However, the association with lymph node involvement or distant metastasis did not reach statistical significance. There was no difference in survival in reference to the expression patterns of CD44v6 and E-cadherin. Furthermore, neither marker was a significant prognostic factor for tumor recurrence and survival according to Cox's multiple variant regression analysis.

Adult↗

PubMed1994

Use of retinoic acids in the treatment of peripheral T-cell lymphoma: a pilot study.

PURPOSE: We have systemically analyzed, both in vitro and in vivo, the effect of 13-cis-retinoic acids (RA) on non-Hodgkin's lymphoma (NHL). METHODS: The in vitro growth-inhibitory effect of 13-cis-RA was examined in 11 (T cell, five; B cell, six) lymphoma cell lines by a tetrazolium colorimetric assay. A pilot clinical trial with oral 13-cis-RA 1 mg/kg/d was conducted in a selected group of 18 lymphoma patients, of whom 16 had failed to respond to at least one regimen of intensive chemotherapy. The in vitro and in vivo effects of 13-cis-RA were correlated with immunophenotypes, RA-induced changes of morphology, and patterns of DNA fragmentation of the lymphoma cells. RESULTS: Four of five T-lymphoma cell lines and none of six B-lymphoma cell lines were sensitive (concentration of 50% growth inhibition [IC50] < 1.5 microns) to 13-cis-RA (P = .015). In the clinical trial, five (two Ki-1, one angioinvasive type, one diffuse mixed cell, and one diffuse large cell) complete remissions and one (Ki1) partial remission were observed in 12 patients with peripheral T-cell lymphoma (PTCL), while none of six patients with B-cell lymphoma responded to 13-cis-RA. 13-cis-RA-induced cellular differentiation and apoptosis, as evidenced by the more mature morphology, characteristic nuclear condensation, and DNA ladder pattern signifying internucleosomal fragmentation, were demonstrated in the sensitive cell lines, as well as in the remitting lymphoma tissues. CONCLUSION: The 13-cis-RA appears to be active on lymphomas of T-lineage and their therapeutic indication may be extended to include some subtypes of PTCL. The mechanisms of action are related to differentiation and apoptosis of lymphoma cells. There appears to be no cross-resistance between 13-cis-RA and conventional chemotherapy.

Adult↗

PubMed1993

Lymphoblast colony-culture assay in acute lymphoblastic leukemia: a quantitative approach.

Lymphoblast colony-culture of adult acute lymphoblastic leukemia (ALL) was studied to explore its clinical implication. Among 13 marrow cultures from ALL patients with full-blown disease, 11 developed leukemic colonies. A type of colony, very similar to a lymphoblastic colony and possibly T-cell in origin, could be found in four cultures of the six control marrows. To minimize the difficulty in differentiating a leukemic blast colony and a normal lymphocyte colony, based solely on morphology, a quantitative approach was used. Since both the mean of blast colony count and the mean of blast percentage of leukemic marrow were significantly higher than those of the control group, mean value plus two standard deviations of the control group were defined arbitrarily as upper normal limits. The defined normal range was then used to examine the relationship between results of the cultures and clinical outcome for the ALL patients. Early relapse or incomplete remission following chemotherapy could be predicted in four patients by these quantitative colony-culture assays 0.5-2 months before full-blown disease. The low colony count and low blast percentage in the colony-culture assay of the fifth patient is compatible with the clinical observation of continuous remission. One culture, growing clusters only, had an increased blast percentage; this correlated well with cytogenetic relapse two months later. In summary, the quantitative colony-culture assay could detect morphologically unidentifiable leukemic cells in ALL patients with early relapse or incomplete remission. This quantitative colony-culture system, though not ultrasensitive in the detection of minimal residual leukemic cells, was of potential value as a prognostic assay.

Adolescent↗

PubMed1992

Hodgkin's disease and non-Hodgkin's lymphoma containing Reed-Sternberg-like giant cells in Taiwan. A clinicopathologic analysis of 50 cases.

Hodgkin's disease (HD) is uncommon in Taiwan. In reviewing the clinicopathologic features of 50 cases, the authors found that the diagnosis of HD was complicated with non-Hodgkin's lymphoma (NHL). Fourteen cases were reclassified as NHL containing Reed-Sternberg (RS) giant cells, mostly peripheral T-cell lymphoma (PTL), and 34 cases as classic HD, which included 8 cases of lymphocyte predominance, 10 of nodular sclerosis, 12 of mixed cellularity, and 4 of lymphocyte depletion. For cases of HD, there was a bimodal age-incidence distribution with peaks at the third and fifth decades; 61.8% manifested Stage B symptoms and 80.6% had Stage III/IV disease. The group of patients with NHL, compared with those with classic HD, was found to be older (mean age, 41.4 years versus 33.1 years; P less than 0.05), to have more extranodal disease (35.7% versus 8.8%, P less than 0.05), less complete remission rate (25% versus 67.9%, P less than 0.05), and shorter median survival (29 months versus 90 months). Most of the NHL patients originally were diagnosed as having atypical or unclassified HD. Thus, the authors conclude that the previous observation of a predominance of mixed cellularity HD in Asian regions may be attributable to the inclusion of PTL, which may mimic HD in histology. Because there is a marked difference in clinical behavior and prognosis, it is important to distinguish between HD and NHL containing RS giant cells in an area with a high incidence of PTL.

Adult↗

PubMed1992

Late survival of non-small cell lung cancer patients with brain metastases. Influence of treatment.

The presence of brain metastasis in lung cancer patients is a highly unfavorable event that usually allows only palliative treatment. A retrospective study was conducted to evaluate the prognostic factors in patients with non-small cell lung cancer (NSCLC) associated with brain metastases. From July 1984 through June 1990, a total of 50 patients with NSCLC associated with symptomatic brain metastasis seen at National Taiwan University Hospital were included. Patients who had incomplete cancer staging workup or loss of follow-up were excluded. Several possible prognostic variables were analyzed initially with univariate analysis and subsequently with multivariate analysis with maximal partial likelihood ratio test in the Cox model. In the univariate analysis, several factors, including number of brain metastases, treatment for brain metastasis with brain tumor resection (BTR) or whole brain radiation therapy (WBRT), and chemotherapy (C/T) after brain metastasis were found to have significant influence on the survival. However, in the multivariate analysis, patients receiving BTR, WBRT, and/or C/T lived significantly longer. The median survival of patients treated with BTR was nine months, eight months in patients with C/T, and seven months in patients with WBRT. Taken together, these patients had a median survival of seven months, which was significantly longer than patients treated with supportive care only (with a median survival of two months). Treatment of brain metastases with WBRT, BTR, C/T, or in combinations also improved the quality of life. We conclude that NSCLC patients with brain metastases should be more aggressively treated with WBRT, BTR, C/T, or in combinations than supportive care only.

Adult↗

PubMed1990

Deletion of the human retinoblastoma gene in primary leukemias.

As an initial step in evaluating the role of tumor suppressor genes in leukemogenesis, we surveyed primary leukemia cells from 130 patients for possible deletion of the retinoblastoma susceptibility (Rb) gene by Southern blot analysis. Two of them clearly showed homozygous deletion of Rb alleles. The first patient was a pre-B acute lymphoid leukemia (ALL) associated with a cytogenetic translocation: t(14;16)(q24;q22). The deletion was located at the 3' portion of the Rb gene, very close to the site of Rb gene deletion recently identified in an ALL cell line. The absence of Rb110 protein was further confirmed by Western blot analysis. The second patient was a chronic myelomonocytic leukemia (CMMoL), terminated in acute blastic transformation. Deletion of the 5' portion of Rb gene was found in leukemic cells in the chronic stage. The results indicated that inactivation of the Rb gene occurred in certain cases of leukemia. Its significance warrants further study.

Aged↗

PubMed1989

Acute graft-versus-host disease: a clinical report and analysis of risk factors.

Of the 31 cases of allogeneic bone marrow transplantation performed in the past 4 years at the National Taiwan University Hospital, 25 evaluable cases were retrospectively studied for incidence, severity, and risk factors of acute graft-versus-host disease (GVHD). The incidence was 60% (15/25) with the proportion of severe form (greater than or equal to grade II) being 53% (8/15). Skin involvement was the most common (13/15), gut the second (5/15), and liver the third (4/15). Most of the diagnosis of skin disease were confirmed by biopsy. Acute GVHD accounted for 3 deaths directly and was the next most common cause of death in post-transplant patients. The long-term survival rate for cases with grade 0-I disease was 65%, and that for those with grade II-III disease was 38%. Multivariate linear regression analysis of risk factors associated with severe form GVHD showed that the diagnosis of aplastic anemia was the most significant factor. Total lymphoid irradiation with or without plasmapheresis in aplastic anemia might contribute to the occurrence of severe acute GVHD.

Acute Disease↗

PubMedDate not supplied

Expression of CD44 and its clinical implication in diffuse-type and intestinal-type gastric adenocarcinomas.

Knowing the differential expression of CD44 isoforms in intestinal- and diffuse-type gastric carcinomas, we used antibodies against the standard form of CD44 (CD44s) and the domain encoded by exon v6 (CD44v6) in 103 patients with primary gastric adenocarcinomas to explore the role of CD44 isoforms in metastases of both types of gastric cancer. Carcinomas of the intestinal type were more frequently CD44s and CD44v6 positive than carcinomas of the diffuse type (p = 0.034 for CD44s and p = 0.022 for CD44v6). The reactivity to these two antibodies did not correlate with histopathological and clinical prognostic factors in intestinal-type carcinoma. In contrast, expression of CD44v6 was associated with infiltrative tumor growth (p = 0.021), depth of invasion (p = 0.012), lymph node involvement (p = 0.005) and a higher incidence of distant metastasis (p = 0.069) in cancers of the diffuse type. CD44s-expressing diffuse-type tumors had a higher incidence of distant metastasis at presentation (p = 0.001), but expression of CD44s was not correlated with other clinicopathologic indices. For all cases, there was a nonsignificant association between CD44s expression and poor survival. Unexpectedly, there was also no significant difference in survival regarding expression of CD44v6 for all cases or the diffuse-type subset. This study showed the role of CD44v6 in invasion and metastases of diffuse-type gastric carcinoma and demonstrated the necessity of subclassifying tumor types when studying the clinical significance of CD44 in human cancers.

Adenocarcinoma↗

PubMedDate not supplied

A phase II study of weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin (HDFL) in the treatment of recurrent or metastatic colorectal cancers.

Previous report suggested that weekly 24-hour infusion of high-dose 5-fluorouracil (5-FU) and leucovorin is a highly active and relatively low toxic regimen for the treatment of colorectal carcinoma (J Clin Oncol 9: 625-30, 1991). This phase II study was conducted to test this important observation by a slightly modified regimen in a larger group of patients. The weekly HDFL regimen consisted of 5-FU 2600 mg/m2/week and leucovorin 300 mg/m2/week (maximum 500 mg) in a 24-hour intravenous infusion. Between February 1992 and December 1995, a total of 42 patients with non-resectable, recurrent or metastatic colorectal adenocarcinoma were enrolled onto the study. Twenty-nine (69.0%) patients had prior exposure to lower-dose 5-FU. There were 22 men and 20 women with median age of 60 (20-75) years. They received a total of 855 and an average of 20.4 (4 to 65) courses of HDFL chemotherapy. Most patients were treated at outpatient clinics and the drugs were infused by an ambulatory pump system via a Port-A catheter. The median duration of follow-up was 22 months. ECOG Gr 2-3 stomatitis, diarrhea, nausea, and vomiting developed in 6 (14.3%), 6 (14.3%), 5 (11.9%), and 5 (11.9%) patients, respectively. Twenty (47.6%) patients had developed hand-foot syndrome. There was no hematological toxicities except 3 (7.1%) patients developed ECOG Gr 1-2 leucopenia. The overall response rate was 42.9% (28%-59%, 95% C.I.) with 2 complete responses and 16 partial responses. Eight (61.5%; 31%-86%, 95% C.I.) of 13 patients, who had no previous 5-FU exposure, responded (1 complete response, 7 partial responses). Ten (34.5%, 17%-54%, 95% C.I.) of 29 patients, who had had previous lower-dose 5-FU exposure, responded (1 complete response and 9 partial responses). The median duration of response was 5 months (1+ to 23+ months). The median overall survival of the whole group of 42 patients and the 18 responders was 10 and 22 months, respectively. Our data supported the original results of HDFL regimen in the treatment of colorectal cancers. HDFL regimen can be used either as first-line or second-line treatment for non-resectable, recurrent or metastatic colorectal cancers.

Adult↗