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Biomedical subjects

Y M Chen

Publications and source records attributed to Y M Chen.

At least 55 records · Page 3Linked to original sources

Non-small cell lung cancer in very young and very old patients.

STUDY OBJECTIVE: A cancer registry was analyzed to determine if the clinicopathologic characteristics, treatment modalities, and prognosis of non-small cell lung cancer (NSCLC) patients < 40 years of age at diagnosis differed from patients > 80 years of age at diagnosis. DESIGN: Retrospective review of patients with NSCLC diagnosed between 1987 and 1996. SETTING: General teaching hospital in Taiwan. PATIENTS: There were 6,048 cases of NSCLC diagnosed during this period. Among them, 127 patients were < 40 years old and 184 patients were > 80 years old. These patients were selected for our study. MEASUREMENTS: Data regarding demographics, presentation symptoms, histology, tumor staging, treatment modality, and survival were obtained from all patients. Pearson's chi(2) test and the Kaplan-Meier method with a log-rank test were used for statistical analysis. RESULTS: We found significantly more female patients (p < 0.001) and adenocarcinoma (p < 0.001) in the younger group, when compared with the older patients. Cough was the most frequent presenting symptom in both age groups, followed by dyspnea, chest pain, and hemoptysis. There was no statistical difference in the severity of the disease in terms of staging between the two age groups. Young patients received surgical intervention more frequently than the aged (p = 0.025). The older patients received only supportive care more frequently (p = 0.011) than the younger patients. Survival was better in young patients, when compared with other patients or aged patients (p < 0.001). CONCLUSIONS: The female sex and adenocarcinoma were predominant in young NSCLC patients, when compared with the older patients. Young NSCLC patients tended to receive more aggressive treatment and had better survival.

Adenocarcinoma↗

A multicenter phase II trial of vinorelbine plus gemcitabine in previously untreated inoperable (Stage IIIB/IV) non-small cell lung cancer.

STUDY OBJECTIVE: Vinorelbine and gemcitabine are two active single agents used in the treatment of non-small cell lung cancer (NSCLC). A clinical trial was conducted to evaluate the efficacy and toxicity of vinorelbine plus gemcitabine in patients with inoperable (stage IIIB or IV) NSCLC. DESIGN: A multicenter phase II study. Vinorelbine, 20 mg/m(2), was given as a 10-min IV infusion, followed by a 30-min IV infusion of gemcitabine, 800 mg/m(2), on days 1, 8, and 15 of each 28-day cycle. PATIENTS AND MEASUREMENTS: From March 1998 to August 1998, 40 patients were enrolled in the study. The efficacy and toxicity of the treatment were recorded. RESULTS: All patients are evaluable for treatment response and toxicity profile. Two patients achieved a complete response, and 27 patients achieved a partial response, with an overall response rate of 72.5% (95% confidence interval, 58.7 to 86.3%). Median survival time was 11 months. The significant (World Health Organization grade, 3/4) toxicities were myelosuppression, including leukopenia (47.5% of patients), anemia (17.5% of patients), and thrombocytopenia (12.5% of patients). However, febrile neutropenia occurred in three patients and accounted for one treatment-related death. Fatigue, or flu-like syndrome, occurred in 17 patients, and the symptoms were reversed spontaneously 1 to 2 days after injection in 10 patients. Another seven patients needed dose reduction to ameliorate symptoms. Interstitial pneumonitis occurred in six patients who recovered after steroid treatment. No patient suffered from grade 3 or 4 nausea/vomiting. CONCLUSION: The combination of vinorelbine and gemcitabine in patients with advanced NSCLC is a highly active non-cisplatin-containing regimen with an acceptable toxicity profile.

Adult↗

Prognosis and recurrent patterns in bronchioloalveolar carcinoma.

STUDY OBJECTIVE: Bronchioloalveolar carcinoma (BAC) is an uncommon pulmonary neoplasm with various radiologic and clinical presentations. In this article, we analyze the initial radiologic findings, TNM stagings, surgical types, and radiologic features of recurrence, and correlate them with patient survival. DESIGN: A retrospective review of 93 patients who underwent resection for BAC from February 1989 to May 1999. PATIENTS: There were a total of 153 patients with BAC diagnosed during this period. Among them, 60 patients (39.2%) had diffuse disease and received medical therapy only, and the remaining 93 patients (60.8%), who had localized disease, underwent surgical resection. Patients who received surgical resection were enrolled in this study. MEASUREMENTS: Data regarding demographics, presentation symptoms, initial radiologic features, surgical type, tumor staging, recurrence status, radiologic patterns of recurrence, and survival were obtained from all patients. RESULTS: Female patients were significantly younger than male patients. Patients who were female, nonsmoking, undergoing curative surgery, lobectomy, or bilobectomy, and with early tumor staging and no nodal involvement had a better prognosis. Patients with a right lung tumor had a longer survival than those with a left lung tumor, with borderline significance. Among those who suffered from recurrent diseases, a second resection yielded a better survival. Multivariate analysis showed curative surgery, initial surgical type, recurrence status, radiologic patterns of recurrence, and duration from surgical resection to recurrence all had a significant impact on survival. CONCLUSIONS: Those patients with localized, early-stage BAC who underwent curative surgery had a better survival. Patients with localized recurrence after the initial surgery warranted a second resection. Those with a diffuse radiologic pattern of recurrence and/or early recurrence had a worse prognosis.

Adenocarcinoma, Bronchiolo-Alveolar↗

Treatment of non-small-cell lung cancer: the Chinese experience in a general teaching hospital.

BACKGROUND: It has been reported that combination chemotherapy and radiotherapy prolongs locally advanced stage IIIB non-small-cell lung cancer (NSCLC) patient survival and cisplatin-based chemotherapy prolongs survival in stage IV disease. This study was aimed at investigating whether this conclusion also applies to Chinese patients. METHODS: We retrospectively reviewed the medical records of NSCLC patients diagnosed at the Taipei Veterans General Hospital covering a period from 1990 to 1996 to examine the effect of treatment regimen on survival. RESULTS: There were 3,925 cases of NSCLC diagnosed during this period. The stage at diagnosis was stage III or IV in the majority (76.6%) of cases. Surgery followed by chemotherapy with or without radiotherapy conferred a survival benefit of more than two years in stage IIIA patients. For stage IIIB patients, chemotherapy in combination with radiotherapy yielded a median survival of 13 months, compared to only seven months for radiotherapy alone. For stage IV patients, cisplatin-based chemotherapy prolonged median survival for more than two months compared with palliative radiotherapy alone or supportive care only. Survival was improved in stage IV patients who received chemotherapy during 1990 to 1996 compared with those who received chemotherapy during 1985 to 1989. This improvement was most likely due to improvements in supportive care because the treatment regimen was constant during the study period. CONCLUSIONS: Cisplatin-based chemotherapy prolonged survival of Chinese patients with metastatic NSCLC. Combination chemotherapy and radiotherapy also prolonged survival of Chinese patients with locally advanced NSCLC.

Carcinoma, Non-Small-Cell Lung↗

Combination chemotherapy with tamoxifen, ifosfamide, epirubicin and cisplatin in extensive-disease small-cell lung cancer.

BACKGROUND: A study of tamoxifen, ifosfamide, epirubicin and cisplatin (TIEP) chemotherapy was conducted in patients with extensive-disease, small-cell lung cancer (SCLC) to assess response and toxicity. METHODS: From November, 1997, to February, 1999, 11 patients were treated, including six chemo-naïve patients and five patients previously treated with cisplatin plus etoposide (EP). The treatment regimen included tamoxifen 60 mg twice daily orally on days 1 to 3, ifosfamide 3 g/m2 intravenous (i.v.) infusion for 60 minutes with mesna on day 2, epirubicin 50 mg/m2 i.v. bolus on day 2 and cisplatin 60 mg/m2 i.v. for 60 minutes on day 2, every 4 weeks for up to six cycles. RESULTS: All patients were evaluated for toxicity and response rate. As expected, the major toxicity was myelosuppression. Grade 3 or 4 leukopenia or neutropenia occurred in all patients during treatment. Two patients (18.2%) experienced fever in association with the neutropenia, one of whom died of sepsis. Grade 3 anemia occurred in two patients (18.2%) during treatment. Toxicities other than neutropenia and anemia were limited. After two cycles of treatment, five of six chemo-naïve patients (83%), and one of five previously treated patients (20%) attained a partial response (overall 54.5%, 95% confidence interval 25%-83.9%). Median survival time was 8.5 and 6 months in chemo-naïve and previously EP-treated patients, respectively. The response rate and median survival time in chemo-naïve patients did not improve compared with a previous study of ifosfamide plus etoposide undertaken 4 years earlier. CONCLUSIONS: Although TIEP is an active combination regimen with an acceptable toxicity profile in Chinese patients with extensive-disease SCLC, it showed no remarkable benefit compared with other regimens used in chemo-naïve patients. The 20% response rate and median survival of 6 months in EP-treated patients deserve further study.

Adolescent↗

Genotypic analysis of HCV infection in kinmen.

In this report, stratified random sampling of an epidemiological study population from the town of Kin-Hu in the Kinmen Islands was used to create a subpopulation of 832 individuals. Two enzyme immunoassays (EIA) were used for antibody testing including Abbott's hepatitis C virus (HCV) EIA 2nd Generation and a synthetic peptide-EIA, NANBASE C-96-EIA, based on the locally predominant strain of HCV. In addition to RIBA and DBL immunoblot assays, reverse transcription-polymerase chain reaction (RT-PCR) was employed to confirm HCV infection. Results showed that 20 of 832 (2.4%) adults in Kinmen had HCV infection. In terms of genotype distribution, 31.3% (5/16) were infected with both 1a and 1b genotypes, 25.0% (4/16) only with the 1b genotype, and 43.8% (7/16) with the 2a genotype. Through comparative analysis of RT-PCR, RIBA, and DBL results, we found that the sensitivities of RIBA and DBL could safely be increased by modifying the definition of a positive case. If the presence of a reactive band with > or = 2+ antibody reactivity to core protein is accepted as positive for overall RIBA or DBL testing, sensitivity is increased without adversely effecting specificity.

Adult↗

The prevalence of NIDDM and IGT and related factors among residents in some areas of Hubei Province, China.

The epidemiological survey of prevalence of NIDDM (non-insulin dependent diabetes mellitus) and IGT(impaired glucose tolerance) was conducted among 9450 residents aged 25-70 in some areas of Hubei Province, China. The results show that NIDDM and IGT prevalences are 2.62% and 4.48%, respectively. There is no significant difference between male and female (P > 0.05). The NIDDM prevalence in cities is slightly higher than that in countryside, but the difference is not significant (P > 0.05). However, the IGT prevalence in city is significantly higher than that in countryside (P < 0.01). The prevalence of both NIDDM and IGT is increasing along with the age of the population. It is also significantly related to the family history of NIDDM, hypertension, and high body mass index (BMI). By using stepwise logistic regression to analyse the risk factors of NIDDM, age (OR = 1.86), BMI(OR = 2.69), family history (OR = 2.84) and hypertension (OR = 2.23) entered the model (significance level is alpha = 0.05).

Adult↗

Molecular characterization of Oryza sativa 16.9 kDa heat shock protein.

A rice class I low-molecular-mass heat shock protein (LMM HSP) Oshsp 16.9 was overexpressed in Escherichia coli. Oligomerized complexes of Oshsp16.9 were harvested and electron microscopic observations of purified complexes revealed globular structures of 10-20 nm in diameter (with majority of 15-18 nm) and calculated to comprise approx. 12 monomers per complex. In comparison, complexes from native rice class I LMM HSPs were observed as larger ellipsoid- or globular-like random aggregated hetero-oligomers. To characterize the biochemical functions of the hydrophobic N-terminal region of Oshsp16.9, a truncation in the N-terminal region was constructed and introduced into E. coli. Results showed that the N-terminal truncated Oshsp16.9 mutant was capable of forming complexes similar to the full-length Oshsp16.9; however, the deletion protein failed to confer in vitro protein thermostability under elevated temperatures. Protein assays from in vivo treatments at higher temperatures exhibited that non-specific interactions of E. coli cellular proteins only occurred with full-length Oshsp16.9 complexes but not with the mutant complex. In vitro immunoprecipitation of cellular proteins from E. coli overexpressing full-length Oshsp16.9 showed that interactions between plant LMM HSP and E. coli cellular proteins are temperature-dependent. Taken together, the hydrophobic N-terminal region of rice class I LMM HSP is critical in the ability of the protein to interact/bind with its potential substrates.

Amino Acid Sequence↗

Differential expression of type 1 angiotensin II receptor mRNA and aldosterone responsiveness to angiotensin in aldosterone-producing adenoma.

Aldosterone secretion in most patients with aldosterone-producing adenomas (APAs) is typically unresponsive to angiotensin II stimulation (AII-unresponsive, AII-U). In some patients, however, plasma aldosterone increases in response to AII stimulation (AII-responsive, AII-R). This differential aldosterone responsiveness could be related to the levels of type 1 AII receptors (AT1R) in the APA. To test this hypothesis, plasma aldosterone levels in response to upright posture and/or sequential high- and low-salt diets were measured by radioimmunoassay in nine patients with APAs. AT1R mRNA levels in the adenomas were quantified by competitive reverse transcription-polymerase chain reaction and correlated to the cellular composition of the adenoma. Two patients were categorised as AII-R by an increase of plasma aldosterone greater than 50% over the baseline. The remaining seven patients who had blunted plasma aldosterone responses were classified as AII-U. Histologically, the AII-R APAs consisted predominantly of zona glomerulosa (ZG)-like cells (> 90%), while the AII-U APAs contained zona fasciculata (ZF)-like cells ranging from 28 to 72%. There was an inverse relationship between the levels of AT1R mRNA in the APA and the percentage of ZF-like cells in the adenoma (n = 9, r = 0.73, P < 0.05). In situ hybridisation findings demonstrated that AT1R mRNA was more uniform and intensive in ZG-like cells than in ZF-like cells. These results suggest that heterogenous aldosterone responsiveness to angiotensin in APAs is histologically dependent and related to the differential expression of AT1R mRNA in the adenoma.

Adenoma↗

Community-based molecular epidemiology of HTLV type I in Taiwan and Kinmen: implication of the origin of the cosmopolitan subtype in northeast Asia.

To understand the possible origin and dissemination of HTLV-I infection in northeast Asia, community-based molecular epidemiological studies were conducted on the Kinmen Islands (off the coast of Fukien Province, China) and in Taiwan. A total of 3831 Taiwanese from 3 townships (Pu-Li, Chu-Dung, and Pu-Tze) and 993 aborigines from 4 tribes in Taiwan participated in this study. The prevalence rates of HTLV-I infection in adult residents from Pu-Li, Chu-Dung, and Pu-Tze were 0.82, 1.72, and 1.63%, respectively. None of the aborigines had HTLV-I infection. Previously, 0.73% of the adult population of Kin-Hu, Kinmen were found to have HTLV-I infection. Peripheral blood mononuclear cells were collected from HTLV-I carriers identified both in Taiwan and Kinmen and the HTLV-I LTR sequences were PCR amplified, subcloned, and sequenced for phylogenetic tree analysis. The results showed that all 6 HTLV-I isolates from Kinmen and 13 of 18 (72.2%) isolates from Taiwan were group a (transcontinental) of Cosmopolitan subtype, while 5 of 18 (27.8%) isolates from Taiwan were group b (Japanese) of Cosmopolitan subtype. Since all of the HTLV-I-infected persons were descendants of immigrants from mainland China, the origin of the Cosmopolitan subtype in Taiwan and Kinmen may not have been Japan, as previously theorized, but China, possibly the result of the migration of an infected population in the past several centuries.

Adult↗

Decreasing levels of anti-Nef antibody correlate with increasing HIV type 1 viral loads and AIDS disease progression.

To study the association between anti-Gag and anti-Nef antibody reactivities and their correlations with disease progression, 174 HIV-1/AIDS patients were followed up for 1 year after they received triple therapy. The antibody reactivities were analyzed using a Western blot test with recombinant Gag and Nef proteins. The results showed that decreasing levels of anti-Gag or anti-Nef antibody correlate with disease progression defined by HIV-1 viral loads or T4 cell counts. After receiving triple treatment for 1 year, 8 of 38 (21.1%) Nef antibody-negative patients became positive, while only 9 of 125 (7.2%) Nef antibody-positive persons lost the antibody reactivity (p < 0.01). Therefore, HIV-1 Nef may serve as a clinical marker of disease progression.

Blotting, Western↗

Pentoxifylline inhibits PDGF-induced proliferation of and TGF-beta-stimulated collagen synthesis by vascular smooth muscle cells.

There is growing evidence that pentoxifylline (PTX) may have potential value as an antiproliferative and antifibrogenic agent. To assess whether this drug may be of use in the prevention of atherosclerosis or restenosis after angioplasty, we investigated the ability of PTX to inhibit proliferation and collagen synthesis in rat vascular smooth muscle cells (VSMCs) under both basal and platelet-derived growth factor (PDGF)- or transforming growth factor-beta (TGF-beta)- stimulated conditions. Intracellular cyclic AMP (cAMP) and cyclic GMP (cGMP) levels were measured in confluent cells using enzyme immunoassay kits. Cell proliferation was measured by methyltetrazolium assay. Cell cycle distribution was determined by flow cytometry. Total collagen synthesis was measured by 3H-proline incorporation assay. Expression of collagen alpha 1(I) and collagen alpha 1(III) mRNAs was detected by northern blotting. Addition of PTX to VSMC cultures suppressed both basal and PDGF-AB (25 ng/ml)-driven cell proliferation, in conjunction with a cell cycle blockade at the G1/S phase at 24 h. This effect was predominantly cAMP-dependent, as PTX increased cAMP in a dose-dependent manner (0.03 to 0.33 mg/ml) but not cGMP level, and the addition of dibutyryl-cAMP (0.2 to 2 m m) closely mimicked the effect of PTX. Furthermore, co-incubation with a selective inhibitor of cAMP-dependent protein kinase (PKA), H-89 (2.0 microm), or an N -myristoylated PKA pseudosubstrate nonapeptide, m-phi PKA (10 microm), prevented the antimitogenic effect of PTX. PTX also suppressed both basal and TGF- beta 1-augmented collagen alpha 1(I) and collagen alpha 1(III) mRNA levels beginning at 24 h, and attenuated both basal and TGF-beta 1 (5 ng/ml)-stimulated total collagen synthesis at 48 h. Co-incubation with H-89 or m-phi PKA reversed PTX-attenuated collagen alpha 1(I) and collagen alpha 1(III) mRNA levels at 24 h. These data suggest that the antimotigenic and anticollagen effects of PTX were mediated predominantly through a cAMP-PKA effector pathway. The dual effect of PTX on VSMC proliferation and collagen synthesis may form the rationale for animal or clinical trials for the treatment of vascular occlusion due to atherosclerosis and restenosis following angioplasty.

Animals↗

Computed tomography of retroperitoneal paragangliomas.

More than 10% of retroperitoneal paragangliomas are malignant. Histopathological appearance is unreliable in distinguishing benign from malignant paragangliomas. In this study the computed tomography (CT) features of retroperitoneal paragangliomas were analysed to determine if benign neoplasms could be distinguished from malignancy by their appearance at imaging. We reviewed the clinical profiles and CT scans of 27 benign and seven malignant retroperitoneal paragangliomas in 32 patients to determine the presence of any characteristic appearances of benign and malignant neoplasms. Extra-adrenal paragangliomas were more frequently malignant (50%) than adrenal neoplasms (12.5%). Benign lesions were generally smaller (average 6.1 cm) than malignant lesions (average 7.9 cm). Benign tumours were more likely to be homogeneous (46.2%) and have well-defined margins (92.3%) than malignant tumours (25 and 12.5% respectively). Larger tumours were more frequently necrotic. Malignant retroperitoneal paragangliomas infiltrated adjacent liver, pancreas, bowel, lymph nodes, blood vessels, or metastasized to bone and liver. Malignant retroperitoneal paragangliomas are frequently extra-adrenal, large and heterogeneous, with ill-defined margin and necrosis. CT is useful for delineating the location, extent and nature of these tumours. Infiltration of surrounding tissues or organs, metastases, and resectability are accurately assessed by CT.

Adolescent↗

Pentoxifylline attenuates experimental mesangial proliferative glomerulonephritis.

BACKGROUND: Accumulation of glomerular macrophages, proliferation of mesangial cells (MCs), and deposition of extracellular matrix proteins are pathobiological hallmarks of glomerulonephritis. We previously reported that a clinically available nonselective inhibitor of cyclic 3',5'-nucleotide phosphodiesterase, pentoxifylline (PTX), inhibits proliferation of cultured rat MCs, as well as collagen production by these cells. In this study, we investigated the in vivo effects of PTX on rat anti-Thy1 disease, a model of mesangial proliferative nephritis. METHODS: Anti-Thy1 nephritis was induced in Sprague-Dawley rats by injecting mouse anti-rat Thy1 antibodies intravenously. Nephritic rats were randomly assigned to receive PTX (0.1 g/kg/day) or vehicle (phosphate-buffered saline) and were sacrificed at various time points. Paraffin kidney sections were stained with hematoxylin and periodic acid-Schiff reagents for glomerular histology. Frozen kidney sections were stained by monoclonal antibodies against proliferating cell nuclear antigen, ED-1, and alpha-smooth muscle actin and were visualized by color development from a horseradish peroxidase reaction. Monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and various extracellular matrix mRNAs were analyzed by Northern blotting. Urine protein concentrations were determined by Lowry's method. RESULTS: Nephritic rats treated with PTX excreted less urinary protein on day 5 of nephritis than vehicle-treated nephritic rats. In periodic acid-Schiff-stained kidneys from PTX-treated nephritic rats, there was attenuation of both glomerular cellularity and glomerular sclerosis compared with vehicle-treated nephritic rats. PTX decreased the augmented glomerular mRNA levels of MCP-1 and ICAM-1 at two hours and on day 1 of nephritis. Immunoreactive staining showed that PTX reduced the number of proliferating glomerular macrophages on days 1, 2, and 3, but not at two hours of nephritis, compared with vehicle-treated nephritic rats. On day 5, PTX decreased the number of activated proliferating MCs and attenuated the glomerular mRNA levels of type I (alpha1), type III (alpha1), and type IV (alpha1) collagen and fibronectin compared with vehicle-treated nephritic rats. CONCLUSION: The administration of PTX to rats with anti-Thy1 disease reduces accumulation and proliferation of glomerular macrophages, attenuates proteinuria, suppresses activation and proliferation of MCs, and ameliorates glomerular sclerosis. These results suggest that PTX may have a suppressive effect in acute phases or relapses of mesangial proliferative glomerulonephritis.

Animals↗

Disconnection of a venous Port-A-Cath followed by embolization after saline flush: rare case report.

A 77-year-old man presented with painful swelling of his Port-A-Cath insertion site soon after flushing with normal saline. No discomfort or abnormality was found during the saline flush. A chest roentgenogram showed that the disconnected catheter had separated from the disc and was absent from its original location. The disconnected catheter was found embolized, by chest roentgenogram and CT scan, to the right atrium and hepatic vein. The patient was treated successfully with an X-ray guided extraction of the catheter. The possibility of catheter disconnection with embolization should be considered and a chest roentgenogram performed immediately in cases of rapid swelling of subcutaneous tissue around the port chamber after fluid infusion.

Aged↗

The status of the do-not-resuscitate order in Chinese clinical trial patients in a cancer centre.

OBJECTIVE: To report and analyse the pattern of end-of-life decision making for terminal Chinese cancer patients. DESIGN: Retrospective descriptive study. SETTING: A cancer clinical trials unit in a large teaching hospital. PATIENTS: From April 1992 to August 1997, 177 consecutive deaths of cancer clinical trial patients were studied. MAIN MEASUREMENT: Basic demographic data, patient status at the time of signing a DNR consent, or at the moment of returning home to die are documented, and circumstances surrounding these events evaluated. RESULTS: DNR orders were written for 64.4% of patients. Patients in pain (odds ratio 0.45, 95% CI 0.22-0.89), especially if requiring opioid analgesia (odds ratio 0.40, 95% CI 0.21-0.77), were factors associated with a higher probability of such an order. Thirty-five patients were taken home to die, a more likely occurrence if the patient was over 75 years (odds ratio 0.12, 95% CI 0.04-0.34), had children (odds ratio 0.14, 95% CI 0.02-0.79), had Taiwanese as a first language (odds ratio 6.74, 95% CI 3.04-14.93), or was unable to intake orally (odds ratio 2.73, 95% CI 1.26-5.92). CPR was performed in 30 patients, none survived to discharge. CONCLUSIONS: DNR orders are instituted in a large proportion of dying Chinese cancer patients in a cancer centre, however, the order is seldom signed by the patient personally. This study also illustrates that as many as 20% of dying patients are taken home to die, in accordance with local custom.

Adult↗

Differential effects of different cytokines on the tumorigenicity and immunogenicity of murine tumors.

BACKGROUND: Granulocyte-macrophage colony stimulating factor (GM-CSF) or other cytokine gene transfer into tumor cells makes an effective tumor vaccine. However, this technique is time consuming and it is not possible for routine use in every patient. METHODS: The present study was designed to combine use of the irradiated B-16 cell line, a C57BL6 mice melanoma cell line, and cytokine (GM-CSF, interleukin-4 [IL-4], IL-10, or IL-12) manipulation, to enhance effectiveness of the tumor vaccine in prevention or reduction of subcutaneous tumor formation or pulmonary metastases. RESULTS: The results of in vitro studies show that the cytolytic activity of the splenocyte was highest when IL-2 or IL-4 was added to the culture medium. Immune splenocytes demonstrated the same level of cytolytic activity regardless of whether the mice were immunized once, twice or thrice. The proliferation assay was higher in immune splenocytes compared with normal splenocytes. The results of both the subcutaneous and pulmonary tumor growth models showed that immunization alone retarded tumor growth and prolonged survival, and this effect was essentially the same regardless of the frequency of immunization. However, the effect was much stronger when IL-4 was used during immunization in the subcutaneous tumor model, whereas IL-12 was the most optimal cytokine in the pulmonary metastases model. CONCLUSIONS: Different cytokines have different effects on immunization in different animal models even with the same tumor and animal. Careful selection of the appropriate cytokine for tumor vaccine immunization must be considered when different patterns of tumor recurrence are noted in clinical practice.

Animals↗

Depressed cytolytic activity of peripheral blood mononuclear cells in unusually high paclitaxel concentrations: reversal by IL-2 and IL-12.

BACKGROUND: Human lymphocyte function was inhibited by high concentrations of paclitaxel and the effect was reversed by interleukin (IL)-2. However, there was no parallel study determining the relationship between paclitaxel concentrations in the lymphocyte cultures and pharmacokinetic analysis in human patients, nor was there any study on the reversal by cytokines, other than IL-2, of the paclitaxel-induced suppression of lymphocyte cytotoxicity. METHODS: We tested the effect of different doses of paclitaxel with various incubation times on the cytolytic activity of peripheral blood mononuclear cells (PBMNCs) against K-562 target cells. RESULTS: Our results showed that using a schedule similar to that for treating patients with tolerable doses of paclitaxel, no inhibition of cytolytic activity of PBMNCs was seen. When the paclitaxel concentration was increased 10-fold, the cytolytic activity of PBMNCs was significantly reduced. This suppression was reversed by the simultaneous addition of a low dose (10 U/ml) of IL-2 or IL-12. Addition of granulocyte macrophage-colony stimulating factor (10 U/ml) did not affect the cytolytic activity of PBMNCs, whereas addition of IL-4 reduced it. Time kinetic studies revealed that, with the addition of IL-2 or IL-12, most of the mononuclear cellular cytolytic activity recovered within 48 to 72 hours. CONCLUSIONS: These findings suggested that, to reduce the toxicity on mononuclear cellular function when high-dose paclitaxel treatment is elected in clinical practice, paclitaxel should be infused over a longer duration of time, or the treatment should be combined with the administration of a low dose of IL-2 or IL-12.

Antineoplastic Agents, Phytogenic↗