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Biomedical subjects

Yi Xia

Publications and source records attributed to Yi Xia.

At least 19 recordsLinked to original sources

Single-cell profiling of mitochondrial phenotyping-coupled mtDNA genotyping.

Simultaneously profiling mitochondrial DNA (mtDNA) heteroplasmy and phenotypic variability at the single-cell level remains a challenge due to the absence of integrated methods that map mitochondrial genotypes alongside their functional states. We introduce human single-cell mitochondrial phenotype-coupled mtDNA sequencing (scMPCDS), a platform that quantifies mtDNA mutations and heteroplasmy together with mitochondrial membrane potential and reactive oxygen species within individual cells. Unlike bulk sequencing or separate single-omics techniques, scMPCDS directly correlates mitochondrial genomic instability with functional outcomes. Using this approach, we demonstrate that DdCBE-mediated mtDNA editing induces cell-specific off-target mutations in the mitochondrial genome, which coincide with diverse phenotypic changes. Applying scMPCDS to HeLa cells and clear cell renal cell carcinoma tissues, we identify single-cell subpopulations exhibiting distinct mtDNA mutation burdens and altered bioenergetic profiles, implicating potential mitochondrial heterogeneity-driven tumor evolution. Overall, scMPCDS serves as a versatile tool to unravel mitochondrial genotype-phenotype relationships at the single-cell level in both normal and disease states, thereby advancing precise mitochondrial diagnostics and therapeutics.

Humans↗

Climate and soil shape Daqu wheat quality and seed microbiome via rhizosphere taxa and microbial assembly.

The grain quality and seed microbiome of Daqu wheat are fundamental determinants of Daqu fermentation performance; however, the mechanisms by which cultivation environments influence these traits via rhizosphere microbial communities remain unclear. Bacterial and fungal communities across the bulk soil-rhizosphere-seed continuum of three wheat cultivars grown in four ecoregions were characterized using absolute quantitative amplicon sequencing. The rhizosphere microbiome was treated as a central intermediary, while the response variables were seed microbial diversity and grain-quality traits, including starch content, protein content, and grain hardness. Twelve physicochemical properties of soil and 11 climatic factors were integrated into a multidimensional association framework. Environmental conditions exerted stronger influences on both seed quality traits and microbial diversity than cultivar identity. Distinct regional signatures were also evident in rhizosphere microbiomes, with environmental gradients explaining community variation more effectively than geographic distance. Bacterial communities exhibited greater sensitivity to environmental fluctuations than fungi. Mantel analyses identified available nitrogen, precipitation, and atmospheric pressure as significant drivers of core rhizosphere taxa (P&#xa0;<&#xa0;0.05). iCAMP revealed that stochastic processes predominantly governed rhizosphere bacterial assembly, whereas stochastic and deterministic mechanisms jointly shaped fungal assembly. Partial least squares path modeling further uncovered a rhizosphere-mediated environment-seed cascade, wherein sunlight intensity and duration, atmospheric pressure, and soil nitrogen directly or indirectly affected seed wet gluten content, grain hardness, and seed microbial diversity through their influences on rhizosphere microbiota. Rhizosphere bacterial diversity was negatively associated with seed bacterial diversity (path coefficient&#xa0;=&#xa0;-0.118, P&#xa0;<&#xa0;0.05), indicating that rhizosphere communities may shape seed endophytic bacterial assemblages via environmental filtering and competitive interactions. Collectively, these findings elucidate how environments shape the quality and seed microbiomes of Daqu wheat, providing scientific guidance for optimal site selection and the standardized production of high-quality brewing wheat for industrial Baijiu.

Triticum↗

Improved treatment outcome in Chinese children and adolescents with Burkitt's lymphoma and large cell lymphoma by using the modified B-non-Hodgkin's lymphoma-Berlin-Frankfurt-Münster-90 protocol.

OBJECTIVES: This study was designed to evaluate the efficacy and toxicity of the modified B-Non-Hodgkin's Lymphoma (NHL)-Berlin-Frankfurt-Münster (BFM)-90-based protocol in Chinese children and adolescents with Burkitt's lymphoma and large cell lymphoma. METHODS: From September 1997 to August 2005, 55 untreated patients (age less than 20 yr) from a single institution were enrolled. The patients were stratified by risk factors (stage, LDH level and chemotherapy response). All patients were treated with a modified B-NHL-BFM 90 protocol. RESULTS: The median age of the patients was 8 yr (range 1.5-20 yr). Of these patients, 22 (40%) had Burkitt's lymphoma (BKL), 22 (40%) had diffuse large B-cell lymphoma (DLBL) and 11 (20%) had anaplastic large T-cell lymphoma (ALCL). Complete remission (CR) occurred in 45 patients (83%), partial remission (PR) in eight patients (14.5%), and progressive disease (PD) in one patient (1.8%). At a median follow up of 24 months, the event free survival (EFS) for all patients was 85% +/- 5% with 100% for group R1, 84% +/- 7% for group R2 and 72% +/- 13% for group R3, and most notably, 80% +/- 6% for stage III/IV at diagnosis. There was no statistically significant difference (P = 0.96) in EFS among BKL and DLBL and ALCL. The major toxicity complications were myelosuppression and mucositis, but these conditions were tolerated and manageable. CONCLUSIONS: This modified NHL-BFM-90 protocol is very effective for Chinese children and adolescents with BKL and large cell lymphomas, and represented an increase in the cure rates in childhood NHL in China.

Adolescent↗

Discovery of bitriazolyl compounds as novel antiviral candidates for combating the tobacco mosaic virus.

Bitriazolyl compounds were synthesized and their activity against tobacco mosaic virus was assessed. Two of them showed promising antiviral activity and were more potent than the reference compounds. Moreover, these compounds are predicted not to be carcinogenic or mutagenic based on the prediction systems. Therefore, the bitriazolyl compounds may provide interesting new leads or scaffolds for use in further attempts to screen novel antiviral candidates.

Antiviral Agents↗

[Clinical analysis of reactive thymic hyperplasia following chemotherapy for childhood malignant lymphoma].

BACKGROUND & OBJECTIVE: Reactive thymic hyperplasia following chemotherapy for malignant tumors is likely to be misdiagnosed as tumor residue or relapse, therefore, leads to unnecessary treatment. This study was to analyze the clinical features of reactive thymic hyperplasia following chemotherapy for childhood malignant lymphoma. METHODS: Clinical data of 13 children with reactive thymic hyperplasia following chemotherapy for malignant lymphoma, treated from Mar. 1999 to Mar. 2004, were retrospectively analyzed. Of the 13 cases, 5 were Hodgkin's disease (HD), and 8 were non-Hodgkin's lymphoma (NHL). All patients received computed tomography (CT) to evaluate the therapeutic effect. When a new thymic mass emerged, positive electron tomography/computed tomography (PET/CT) was performed to identify its quality. RESULTS: At diagnosis, 10 patients had mediastinal involvement. Reactive thymic hyperplasia occurred following the completion of chemotherapy in 9 cases, or during the maintenance of chemotherapy in 4 cases. CT showed that the longest diameters of the new mediastinal masses were 2.2-6.0 cm (mean 3.7 cm). The interval from last chemotherapy cycle to the occurrence of thymic hyperplasia was 2-12 months (mean 4 months). PET/CT was performed to 5 cases, and showed no vital tumors in the mediastinum. Three cases were misdiagnosed as tumor residue or relapse, and received second-line therapy. All patients were followed-up for 1-6 years (median 4 years), and none suffered tumor relapse. CONCLUSIONS: Reactive thymic hyperplasia may occur following intensive chemotherapy for childhood malignant lymphoma. It should not be misdiagnosed as malignant tumors and overtreated.

Adolescent↗

[Extrapulmonary small cell carcinoma in 52 patients].

BACKGROUND & OBJECTIVE: The majority of small cell carcinoma occurs in the lung. Extrapulmonary small cell carcinoma (ESCC) has been recognized as a clinicopathologic entity distinct from small cell carcinoma of the lung. The study was to investigate the clinical characteristics, therapy, and prognosis of ESCC. METHODS: The medical records, from Jan. 1985 to Dec. 2005, of 53 patients with pathologically proved ESCC were analyzed retrospectively. RESULTS: Of the 53 patients, 39 were men and 14 were women, with the median age of 53 years (range, 27-76 years). Of the 53 cases of ESCC, 33 (62.3%) were detected in the esophagus, 5 in the cervix, 4 in the larynx, 3 in the pharynx, 2 in the upper sinus, 2 in the rectum and sublingual gland, 1 in the thyroid gland, 1 in the pleura, and 1 in the liver. Forty patients (75.5%) had limited disease (LD) and 13 (24.5%) had extensive disease (ED). Patients with ED mostly received platinum-based chemotherapy, for which the response rate was 69.2%. Patients with LD were treated with a variety of therapeutic modalities: 7 were treated with surgery plus radiochemotherapy, 3 with surgery plus radiotherapy, 18 with surgery plus chemotherapy, 6 with radiotherapy plus chemotherapy, 4 with radiotherapy alone, and 2 with chemotherapy alone. The median survival time (MST) was 20 months for all patients, and the 1-and 3-year survival rates were 41.3% and 31.4%. MST for patients with ED and LD were 15 months and 26 months, respectively, and 1-and 3-year survival rates were 51.1% vs. 14.4%, and 42.5% vs. 0% (P=0.017 ). CONCLUSIONS: ESCC is identified in various sites, with the most common primary site being the esophagus. Multimodality therapy has become increasingly used for the majority of patients with LD-ESCC. Combination chemotherapy has been a major treatment for patients with ED-ESCC. Generally, the prognosis of LD-ESCC is significantly superior to ED-ESCC.

Adult↗

[Treatment outcome of children and adolescents with germ cell tumor after combined therapy---a report of 44 cases].

BACKGROUND & OBJECTIVE: The overall survival rate of children and adolescents with germ cell tumor is more than 75% after adopting combined therapy. However, the prognosis varies with stage, pathologic type, and primary tumor site. This study was to analyze the clinical characteristics and treatment outcome of children and adolescents with germ cell tumor, and to investigate the prognostic factors and therapeutic strategy. METHODS: Clinical characteristics, treatment outcome, and prognostic factors of 44 children and adolescents with germ cell tumor, treated in Cancer Center of Sun Yat-sen University from Jan. 1997 to Dec. 2005, were analyzed. Survival rate was calculated by Kaplan-Meier method. RESULTS: Of the 44 patients, 25 received adjuvant chemotherapy after operation; 1 received operation alone; 18 received induction chemotherapy. Of the 18 patients, 7 received tumor resection after chemotherapy; 2 patients with primary mediastinal chorioepithelioma with multiple metastases received radiotherapy on residual disease after chemotherapy; 1 patient with postoperative abdominal metastasis and 1 with postoperative lung metastasis achieved complete remission after chemotherapy; 1 patient with mediastinal sinus tumor achieved partial remission after chemotherapy; 6 had poor response to chemotherapy and died of disease progression. Chemotherapy-treated patients received platinum-containing regimens for 2-7 cycles. The median follow-up was 32 months. The overall 3-year survival rate was 84.8%. The 3-year survival rate was 100% for stage I-II patients, 83.3% for stage III patients, 65.6% for stage IV patients, and 66.7% for relapsed patients. For previously untreated patients, the 3-year survival rate was 96.0% for gonadal germ cell tumor patients and 61.0% for extragonadal germ cell tumor patients. CONCLUSION: Surgery combined with platinum-containing chemotherapy can improve efficacy and survival of children and adolescents with germ cell tumor. For the patients with stage IV, relapsed, and metastatic tumors, novel therapeutic regimens with increased dose intensity need further investigation.

Adolescent↗

[Efficacy of chemotherapy regimen using ifosphamide and carboplatin on recurrent or refractory neuroblastoma].

BACKGROUND & OBJECTIVE: About 30% of neuroblastoma patients have poor response to first-line chemotherapy or progress during chemotherapy. Although advanced neuroblastoma patients could achieve complete remission after combined treatment, most of them relapsed finally. This study was to evaluate the efficacy of ifosphamide and carboplatin as a salvage chemotherapy regimen on recurrent or refractory neuroblastoma. METHODS: Nine refractory neuroblastoma patients and 23 recurrent neuroblastoma patients were treated with ifosphamide (1.5 g/m(2) daily for 5 days) and carboplatin (400 mg/m(2) on day 1). Mesna was applied at a dosage of 20% of ifosfamide 3 times at 4-hour intervals after termination of the ifosfamide infusion. Chemotherapy was administered every 2-3 weeks. RESULTS: None of the 32 patients achieved complete remission; 19 (59.4%) achieved partial remission. The median remission time was 4.2 months (1-28 months). After chemotherapy, 8 patients received operation to resect tumors. Main adverse events included grade III-IV neutropenia (44.7%), grade III-IV thrombocytopenia (53.1%), neutropenia accompanied with infection (18.8%), grade I liver dysfunction (12.5%), and hemorrhagic cystitis (9.4%). All adverse events were reversible. CONCLUSIONS: Recurrent and refractory neuroblastoma responds well to chemotherapy regimen of ifosphamide plus carboplatin. The toxicities are tolerable. But the long-term prognosis is poor. More effective strategies are needed to improve its long-term survival.

Adolescent↗

Photolabeling probes of ribavirin and EICAR.

Ribavirin, the only small molecule available so far for treating hepatitis C virus infection, was recently used in an emergency context to treat patients with severe acute respiratory syndrome in the early stages of the disease. EICAR, one of the most potent congeners of ribavirin, has 10 to 100 times greater antiviral potency than ribavirin. The mechanisms underlying the antiviral effects of ribavirin and EICAR have not yet been definitely elucidated, but they seem to be similar. In order to study the mechanisms responsible for their antiviral effects using a photolabeling approach, we have developed photolabeling probes of ribavirin and EICAR, in which an azido group was introduced into the pseudobases of triazole and imidazole, respectively. The ribavirin photoprobes were obtained by directly coupling the azidotriazole to the protected ribose sugar, while the EICAR probe was prepared by diazotizing AICAR and subsequently substituting with NaN3. All these probes showed a fast, clear-cut photochemical reaction, which suggests that they are promising tools for use in photolabeling studies.

Antiviral Agents↗

The influence of cortical end-plate on broadband ultrasound attenuation measurements at the human calcaneus using scanning confocal ultrasound.

Quantitative ultrasound (QUS) assessment, including broadband ultrasound attenuation (BUA), is an efficient technique for assessing bone quality in various statuses, e.g., osteoporosis. While assessing trabecular bone loss is essential to bone quality, the existence of cortical bone can substantially reduce the accuracy of BUA measurement. In this study, we developed an approach to quantify the influence of the cortical end-plate in the QUS on 18 cadaver calcanei using both analytical and experimental analyses. A simplified cortical-trabecular-cortical sandwich model has been developed for simulation of wave propagations. Results show that the cortical end-plate has a significant effect on BUA (yielding 8.5 +/- 3.6 dB/MHz in cortical bone alone), approximately 15% of the BUA value over the whole bone BUA measurement (54.1 +/- 20.1 dB/MHz). The phenomenon has been predicted by the developed analytical model with a high correlation (r2 = 0.63, p < 0.0001). The data have suggested that the mechanism of the BUA attributed to the cortical end-plate is primarily due to the ultrasonic wave transmission and reflection within the cortical layers. Therefore, the influence of the cortical end-plate in BUA can be quantified and incorporated into the QUS assessment for bone quality, which may provide insight into BUA measurement for accurate diagnosis of bone diseases.

Bone Density↗

[Efficacy of short-term and intensive chemotherapy for the treatment of childhood and adolescent B cell non-Hodgkin's lymphoma].

OBJECTIVES: To evaluate the efficacy and toxicity of the B-NHL-BFM-90 protocol in the treatment of Chinese childhood and adolescent B-cell non-Hodgkin's lymphomas (B-NHL). METHODS: Forty-two untreated childhood and adolescent B-NHL were enrolled in the present study. Of them 18 cases were Burkitt's lymphoma, 16 diffuse large B cell lymphoma and 8 anaplastic lymphoma. There were 10 cases in stage II and 32 in stage III/IV. The patients were grouped by risk factors into low, medium and high risk groups. All patients were treated with the B-NHL-BFM 90 (Berlin-Frankfurt- Münster) protocol. The low risk group received A, B courses for 4 cycles, the medium risk group AA, BB courses for 6 cycles, and the high risk group AA, BB, CC courses for 6 cycles. RESULTS: Complete remission (CR) was obtained in 37 patients (88%), and partial remission (PR) in 5 (12%). Of the 5 PR patients, I received autologous hematopoietic stem cell transplantation, 3 received radiotherapy for residual disease and 1 just under watching. Major toxicity was myelosuppression and mucositis, especially in AA, BB and CC cycles, but was tolerant and manageable. Median follow-up was 20 (4 - 89) months. Kaplan-Meier method was used to analyse survival data. Two year event free survival (EFS) for all patients was 86. 24%, being 100% for stage II and 80.95% for stage III/IV. CONCLUSION: Short term and intensive chemotherapy can improves the efficacy and survival rate of childhood and adolescent B-NHL, especially for advanced stage patients.

Adolescent↗

Anti-AIDS agents. Part 56: Synthesis and anti-HIV activity of 7-thia-di-O-(-)-camphanoyl-(+)-cis-khellactone (7-thia-DCK) analogs.

Two thia-DCK analogs (3a,b) were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. Compound 3a showed potent anti-HIV activity with an EC50 value of 0.14 microM and a therapeutic index of 1110. However, the corresponding 6-tert-butyl-substituted compound (3b) showed no suppression. The bioassay results indicated that thia-DCK analogs merit attention as potential HIV-1 inhibitors.

Anti-HIV Agents↗

Anti-AIDS agents. Part 62: anti-HIV activity of 2'-substituted 4-methyl-3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (4-methyl DCK) analogs.

Four 4-methyl-3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (4-methyl DCK) analogs (7a-d) with different alkyl substituents at the 2'-position were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. 2'-Methyl-2'-ethyl-4-methyl DCK (7b) was more potent (EC(50)=0.22 microM, TI>175) than the other three compounds (7a, 7c, and 7d), but significantly less potent than 4-methyl DCK (2, EC(50)=0.0059 microM, TI>6600). The bioassay results indicated that the 2'-substituents had a strong effect on the anti-HIV activity, and gem-dimethyl substitution at the 2'-position was greatly preferable to larger alkyl substituents or hydrogen atoms.

Anti-HIV Agents↗

Anti-AIDS agents. Part 58: synthesis and anti-HIV activity of 1-thia-di-O-(-)-camphanoyl-(+)-cis-khellactone (1-thia-DCK) analogues.

Two 1-thia-DCK analogues (9a and 9b) were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. Compound 9a showed excellent anti-HIV activity with an EC(50) value of 0.00012 microM and therapeutic index of 1408000. Compound 9b was less active with EC(50) and TI values of 3.11 microM and 62.3, respectively. The bioassay results indicated that thia-DCK analogues merit attention as potential HIV-1 inhibitors.

Anti-HIV Agents↗

[Comparing CHOP, CHOP+HD-MTX,and BFM-90 regimens in the survival rate of children and adolescents with B cell non-Hodgkin's lymphoma].

BACKGROUND & OBJECTIVES: B cell non-Hodgkin's lymphoma (B-NHL) in childhood and adolescence is aggressive. Routine CHOP regimen can improve the survival rate of patients with early-stage disease, but its effect on patients with advanced disease was poor. Therefore, it is worthwhile to further investigate how to treat patients with B-NHL at different stages. This study was designed to retrospectively analyze and compare CHOP, CHOP+HD-MTX, and BFM-90 regimens in the survival rate of children and adolescents with B-NHL,and explore the optimal therapeutic strategy and protocols. METHODS: Thirty cases of 3- to 17-year-old untreated patients with B-NHL were enrolled in CHOP group, with 13 in Stage I/II, and 17 in stage III/IV (St Jude staging), all patients received standard CHOP for 2 to 8 cycles, the regimen was repeated every 3 weeks. Eighteen cases of 3- to 14-year-old untreated patients with B-NHL were enrolled in CHOP+HD-MTX group, with 6 in Stage I/II, and 12 in stage III/IV (St Jude staging), all patients received CHOP+HD-MTX and intrathecal injection for 2 to 8 cycles, the regimen was repeated every 4 weeks. Twenty-five cases of 1.5- to 15-year-old untreated patients with B-NHL were enrolled in BFM-90 group, with 7 in Stage I/II,and 18 in stage III/IV (St Jude staging). The patients with stage I/II disease received A schema alteration with B schema of BFM-90 regimen for 4 to 6 cycles, while the patients with stage III/IV disease received AA schema alteration with BB schema of BFM-90 regimen for 6 cycles, the interval of cycles was 18-21 days. The survival rates were evaluated by Kaplan-Meier method. RESULTS: In CHOP group,complete response (CR) rate was 70% (21/30), and partial response (PR) rate was 13% (4/30). In CHOP+HD-MTX group, CR rate was 83%, PR rate was 16%. In BFM-90 group, CR rate was 96% (24/25), and PR rate was 4% (1/25). The hematologic toxicity incidence was higher in BFM-90 group than in the other 2 groups. In CHOP group, the overall 2-year survival rate was 52.79% (72.73% for Stage I/II, and 37.82% for stage III/IV). In CHOP+HD-MTX group, the overall 2-year survival rate was 55.56 % (83.33 % for Stage I/II, and 41.67 % for stage III/IV). There was no significant difference between CHOP group and CHOP+HD-MTX group in survival rate (P=0.78). In BFM-90 group,2-year event-free survival rate (EFS) was 84.01 % (100% for Stage I/II, and 77.04 % for stage III/IV). The differences in survival rate between BFM-90 group and CHOP group, CHOP+HD-MTX group were both significant (P=0.013, and P=0.034). CONCLUSION: BFM-90 regimen can greatly improve the survival rate of children and adolescents with B-NHL, especially of patients with advanced NHL. CHOP, and CHOP+HD-MTX regimens work better for the early stage patients, but produce low survival rate for patients with advanced NHL. A high intensive chemotherapy like BFM-90 regimen is necessary for children and adolescents with advanced B-NHL.

Adolescent↗

[Primary study of relationship between serum level of VEGF and non-Hodgkin's lymphoma in children and adolescent patients].

BACKGROUND & OBJECTIVE: Angiogenesis is an important mechanism in morbility of malignant tumor, vascular endothelial growth factor (VEGF) is the key factor. This study was to investigate the serum level of VEGF in children and adolescent patients with non-Hodgkin's lymphoma (NHL). METHODS: The serum levels of VEGF(sVEGF) in 24 pretreated NHL patients were detected by ELISA. sVEGF in 10 of the 24 patients who received complete response after treatment were also detected by ELISA. RESULTS: The average serum VEGF level was 745.79 ng/L (40.64-3623.09 ng/L)in 24 NHL patients. It was higher than normal [(294.20+/-23.40) ng/L]. sVEGF in 18 of the patients were higher than the standard, while in 6 of the patients were lower than the standard. The average serum VEGF level was 289.54 ng/L (35.11-826.8 ng/L) in 10 of The CR patients, 8 cases of them had a high VEGF level before treatment but a nearly normal level after first CR. And 2 cases of them had normal level during the course. CONCLUSIONS: The serum level of VEGF in NHL patients was higher than normals. The high serum level of VEGF has a tendency to drop to the normal standard after receiving CR. From the clinical data, a high serum level was not found associated with stage, gender, PS. score, IPI score, serum LDH and "B" symptoms et al.

Adolescent↗

[Efficacy of modified BFM-90 regimen on children and adolescents with T cell lymphoblastic lymphoma: a report of 20 cases].

BACKGROUND & OBJECTIVE: T-cell lymphoblastic lymphoma in childhood and adolescence is an aggressive malignant disease with higher mortality. BFM-90 regimen for lymphoblastic lymphoma is one of the most effective regimens. This study was designed to evaluate efficacy and toxicities of modified BFM-90 regimen on Chinese children and adolescents with lymphoblastic lymphoma. METHODS: A total of 20 naive children and adolescents with T cell lymphoblastic lymphoma were enrolled, 7 in stage III, and 13 in stage IV. Eighteen (90%) patients suffered from mediastinal mass with superior vena obstruction syndrome,10(50%) suffered from marrow invasion. All patients received modified BFM-90 regimen consisting of induction, consolidation and central nervous system prophylaxis, reinduced alleviation, and maintenance therapy. Total treatment duration was 2 years. Kaplan-Meier method was used to evaluate long-term survival rate. RESULTS: After induction remission,18 patients (90%) achieved complete remission (CR), 1 had partial remission (PR), and 1 had progressive disease (PD), overall response rate was 95%. The 2 patients with PR or PD died of tumor progression. Of 2 patients at CR1 received APBSC, 1 relapsed after transplantation, but achieved CR and survived after salvage chemotherapy;1 survived all along. Of other patients achieved CR, 5 relapsed; of these 5 patients, 1 survived after allogeneic stem cell transplantation, 1 survived after autologous stem cell transplantation, 3 died of progressive disease after chemotherapy. The overall 3-year survival rate was 74%. All patients had myelosuppression of grade III-IV during the induction and reinduction phases, but the hemotologic toxicity was manageable. CONCLUSIONS: Modified BFM-90 regimen is feasible for Chinese children and adolescent patients with lymphoblastic lymphoma, and may improve survival rate of these patients. The major side effect is myelosuppression, but it is manageable.

Adolescent↗

Antitumor agents. Part 226: synthesis and cytotoxicity of 2-phenyl-4-quinolone acetic acids and their esters.

2-Phenyl-4-quinolone acetic acids and their esters were synthesized and evaluated for interaction with tubulin and for cytotoxicity against a panel of human tumor cell lines. 2-Phenyl- and 2-(2'-fluorophenyl)-4-quinolone-8-acetic acids (11 and 12) displayed potent cytotoxicity with ED(50) values at nanomolar concentrations, but had minimal activity against tubulin polymerization. 2-(2'-Fluorophenyl)-4-quinolone-6-acetic acid (3) and 2-(2'-fluorophenyl)-4-quinolone-8-acetic acid methyl ester (10) moderately inhibited tubulin polymerization.

Acetates↗