Biomedical subjects

Jing Jin

Publications and source records attributed to Jing Jin.

At least 37 records · Page 2Linked to original sources

PubMed2006

[Comparison of preliminary results of involved-field with extended field radiotherapy combined with chemotherapy for early stage Hodgkin's disease].

OBJECTIVE: To evaluate whether involved-field (IF) radiotherapy is equally effective and less toxic in comparison with extended-field (EF) radiotherapy for patients with early-stage Hodgkin's disease (HD) who received combined modality therapy. METHODS: The data of 88 early-stage HD patients treated with combined modality therapy were retrospectively reviewed. According to Ann Arbor classification, 12 patients (13.7%) had stage IA disease, 56 stage IIA (63.6%), and 20 IIB (22.7%). Forty-two (47.7%) patients underwent involved field radiotherapy (IF group), whereas the other 46 (52.3%) received extended field radiotherapy (EF group). RESULTS: Of 6 patients who developed recurrence, 3 (7.1%) were in IF group and the other 3 (6.5%) in EF group. Only one patient's recurrence developed inside the radiation field in EF group. Three patients (7.2%) in IF group and 9 (19.5%) in EF group had WHO grade 1 and 2 leukopenia (P = 0.089). Overall survival rate at 1-, 2- and 3-year was 100.0%, 97.1%, and 97.1% in IF group versus 100.0%, 100%, and 95.8% in EF group (P = 0.86), respectively. Freedom from progression survival rate at 1-, 2- and 3-year was 97.6%, 94.8%, and 91.7% in IF group versus 97.8%, 93.2%, and 93.2% in EF group (P = 0.65), respectively. CONCLUSION: Compared with extended-field radiotherapy, involved-field radiotherapy is equally effective and less toxic for patient with early-stage Hodgkin's disease treated with combined modality therapy.

Adolescent↗

PubMed2006

[Phase I study of postoperative concurrent chemoradiation with capecitabine as adjuvant treatment for stage II/III operable rectal cancer].

OBJECTIVE: This phase I study is to determine the maximal tolerated dose and the dose-limiting toxicity of capecitabine combined with standard radiotherapy (RT) as postoperative adjuvant treatment for rectal cancer patients. METHODS: Stage II/III rectal cancer patients 18 - 75 years of age had undergone curative surgery with Karnofsky score > or = 70% were eligible to be included in this study. Total dose of RT DT 50 Gy was delivered to the pelvic area in fraction of 2.0 Gy per day for 5 weeks. Capecitabine was orally administered concurrently with radiotherapy for a total of 2 cycles in escalating doses: twice daily at 12 hour interval for consecutive 14 days as one cycle, separated by a seven day rest, then followed by another cycle. From March 2004 to May 2005, 24 patients were included and treated at the following dose levels: daily 1000 mg/m(2) (3 patients), 1200 mg/m(2) (3 patients), 1400 mg/m(2) (3 patients), 1500 mg/m(2) (3 patients), 1600 mg/m(2) (6 patients), and 1700 mg/m(2) (6 patients). Dose-limiting toxicities (DLT) including grade 3 or grade 4 hematologic and nonhematologic toxicity were observed. RESULTS: Dose-limiting toxicity was observed in one patient treated at dose of 1600 mg/m(2) with grade 3 diarrhea, and in 2 patients at dose of 1700 mg/m(2) with one grade 3 and one grade 4 diarrhea. CONCLUSION: Diarrhea is the most common dose-limiting toxicity. In our study, the maximal tolerated dose (MTD) of capecitabine given concurrently with radiotherapy was daily 1600 mg/m(2), from D1 to D14 separated by 7-day rest for 2 cycles. Capecitabine given concurrently with standard radiotherapy is safe and tolerable for operated stage II/III rectal cancer patients.

Adolescent↗

PubMed2006

[Expression profile of nasal NK/T cell lymphoma by cDNA microarray].

OBJECTIVE: To investigate the changes of gene expression profile in nasal NK/T cell lymphoma. METHODS: Total RNA was extracted from the fresh nasal NK/T cell lymphoma tissue and normal lymph node. Fluorescent labeled cDNA was obtained through synthesizing process by reverse transcription. After hybridization in the two identical microarrays consisting of 4096 genes, overexpressed or underexpressed tumor related genes were analyzed. RESULTS: In both experimental group and control group, there were six samples. A total of 365 (8.9%) genes was found to be differentially expressed by a factor of twofold or greater in both of two identical cDNA microarrays, which included oncogenes, tumor supressor genes, cell cycle regulators, apoptotic and antiapoptotic factors, DNA transcription factors, DNA repair and recombination factors, signal transduction genes, protein translation genes, as well as a large number of metabolic genes. Thirty-seven of these genes were found to be differentially expressed by a factor of fourfold or greater. The biochemical functions of these differentially expressed genes were diverse. CONCLUSION: This study demonstrates that many different kinds of genes are possibly involved in the initiation and progression of nasal NK/T lymphoma. cDNA microarray technique is useful in screening cancer gene expression for nasal NK/T lymphoma.

Antigens, CD20↗

PubMed2005

[Clinical evaluation of emergency liver transplantation for patients with benign end-stage liver diseases].

OBJECTIVE: To evaluate the efficacy of emergency liver transplantation in treating patients with benign end-stage liver diseases and explore the possible prognostic factors. METHOD: The clinic data of 46 cases of recipients who underwent ELT were retrospectively analyzed. clinicopathological variables (including age, gender, etiology, serum creatinine, PT, INR, albumin, total bilirubin) were compared between the survival group (n = 32) and the dead group (n = 14). And the prognostic values of CTP and MELD score were analyzed. RESULTS: Higher serum creatinine level, MELD score and CTP score were found in the dead group, as compared to those in survival group. The survival rates among CTP or MELD categories showed significant difference. Three-and six months and one year survival rates of total recipients were 73.9% , 71.7% and 69.6% respectively. CONCLUSION: Emergency liver transplantation is an effective treatment to salvage patients in end-stage. Serum creatinine is the important prognostic factor to the posttransplant survival. MELD score system is more sensitive than CTP classification in predicting the prognosis.

Adult↗

PubMed2005

A phase I study of concurrent radiotherapy and capecitabine as adjuvant treatment for operable rectal cancer.

PURPOSE: To determine the maximum tolerated dose and the dose-limiting toxicity of capecitabine with standard radiotherapy (RT) as adjuvant treatment in patients with rectal cancer. METHODS AND MATERIALS: Patients with Stage II/III rectal cancer after surgery were eligible. Total RT dose was delivered as DT 50 Gy in fractions of 2.0 Gy/day for 5 weeks to the pelvic area. Capecitabine was administered concurrently with RT in escalating doses, twice daily with a 12-h interval, for two cycles of 14 days separated by a 7-day rest. Dose-limiting toxicity included Grade 3 or Grade 4 hematologic and nonhematologic toxicity. RESULTS: Twenty-four patients were enrolled at the following dose levels: 1,000 (3 patients), 1,200 (3 patients), 1,400 (3 patients), 1,500 (3 patients), 1,600 (6 patients), and 1,700 mg/m2/day (6 patients). Dose-limiting toxicity was observed in 1 patient at 1,600 mg/m2/day (Grade 3 diarrhea) and in 2 patients at 1,700 mg/m2/day (1 patient had Grade 3 and 1 Grade 4 diarrhea). CONCLUSION: The maximum tolerated dose (MTD) of capecitabine given concurrently with RT was 1,600 mg/m2, daily from the 1st to the 14th day, with a 7-day rest, for two cycles.

Adult↗

PubMed2005

Functions of early (AP-2) and late (AIP1/ALIX) endocytic proteins in equine infectious anemia virus budding.

The proline-rich L domains of human immunodeficiency virus 1 (HIV-1) and other retroviruses interact with late endocytic proteins during virion assembly and budding. In contrast, the YPDL L domain of equine infectious anemia virus (EIAV) is apparently unique in its reported ability to interact both with the mu2 subunit of the AP-2 adaptor protein complex and with ALG-2-interacting protein 1 (AIP1/Alix) protein factors involved in early and late endosome formation, respectively. To define further the mechanisms by which EIAV adapts vesicle trafficking machinery to facilitate virion production, we have examined the specificity of EIAV p9 binding to endocytic factors and the effects on virion production of alterations in early and late endocytic protein expression. The results of these studies demonstrated that (i) an approximately 300-residue region of AIP1/Alix-(409-715) was sufficient for binding to the EIAV YPDL motif; (ii) overexpression of AIP1/Alix or AP-2 mu2 subunit specifically inhibited YPDL-mediated EIAV budding; (iii) virion budding from a replication-competent EIAV variant with its L domain replaced by the HIV PTAP sequence was inhibited by wild type or mutant mu2 to a level similar to that observed when a dominant-negative mutant of Tsg101 was expressed; and (iv) overexpression or siRNA silencing of AIP1/Alix and AP-2 revealed additive suppression of YPDL-mediated EIAV budding. Taken together, these results indicated that both early and late endocytic proteins facilitate EIAV production mediated by either YPDL or PTAP L domains, suggesting a comprehensive involvement of endocytic factors in retroviral assembly and budding that can be accessed by distinct L domain specificities.

Adaptor Protein Complex 2↗

PubMed2005

Primary early-stage intestinal and colonic non-Hodgkin's lymphoma: clinical features, management, and outcome of 37 patients.

AIM: To analyze the clinical features, management, and outcome of treatment of patients with primary intestinal and colonic non-Hodgkin's lymphoma (PICL). METHODS: A retrospective study was performed in 37 patients with early-stage PICL who were treated in our hospital from 1958 to 1998. Their clinical features, management, and outcome were assessed. Prognostic factors for survival were analyzed by univariate analysis using the Kaplan-Meier product-limit method and log-rank test. RESULTS: Twenty-five patients presented with Ann Arbor stage I PICL and 12 with Ann Arbor stage II PICL. Thirty-five patients underwent surgery (including 31 with complete resection), 22 received postoperative chemotherapy or radiotherapy or both. Two patients with rectal tumors underwent biopsy and chemotherapy with or without radiotherapy. The 5- and 10-year overall survival (OS) rates were 51.9% and 44.5%. The corresponding disease-free survival (DFS) rates were 42.4% and 37.7%. In univariate analysis, multiple-modality treatment was associated with a better DFS rate compared to single treatment (P = 0.001). While age, tumor size, tumor site, stage, histology, or extent of surgery were not associated with OS and DFS, use of adjuvant chemotherapy significantly improved DFS (P = 0.031) for the 31 patients who underwent complete resection. Additional radiotherapy combined with chemo-therapy led to a longer survival than chemotherapy alone in six patients with gross residual disease after surgery or biopsy. CONCLUSION: Combined surgery and chemotherapy is recommended for treatment of patients with PICL. Additional radiotherapy is needed to improve the outcome of patients who have gross residual disease after surgery.

Adolescent↗

PubMed2005

Chronic activation of protein kinase Bbeta/Akt2 leads to multinucleation and cell fusion in human epithelial kidney cells: events associated with tumorigenesis.

Most cancers arise from the stepwise accumulation of genetic changes. There is also evidence for defects in the machinery and checkpoints for maintenance of normal diploid chromosome complements, resulting in genetic instability that helps fuel the accumulation of mutations that contribute to the development of cancer. The proto-oncogene protein kinase B (PKB/Akt), and its regulators including phosphatidylinositol 3' kinase and PTEN, has been shown to play critical roles in the regulation of multiple cellular functions such as transcription, cell survival, cell cycle progression, angiogenesis and cell motility--all of which are important to the malignant process. Here, we report the use of a membrane targeted PKBbeta, the activation of which is under the control of a 4-hydroxy-Tamoxifen-responsive estrogen-receptor (ER) ligand binding domain. Induction of PKBbeta-ER activity in human kidney epithelial cells (HEK293) resulted in changes in cellular growth, size, and in the appearance of aneuploid cells. Over time, in a PKBbeta-dependent manner, cells also underwent extensive multinucleation caused due to a combination of both endomitosis and cell fusion. These findings suggest that chronic activation of PKBbeta may contribute to genetic instability and autophagy, properties commonly found in tumor cells.

Cell Fusion↗

PubMed2005

A tumor necrosis factor receptor family protein serves as a cellular receptor for the macrophage-tropic equine lentivirus.

Characterization of cellular receptors for human, simian, and feline immunodeficiency viruses that are tropic for lymphocytes and macrophages have revealed a common theme of a sequential binding of viral envelope proteins with two coreceptors to mediate virus infection of target cells. In contrast to these dual tropic immunodeficiency viruses, the ungulate lentiviruses, including equine infectious anemia virus (EIAV), exclusively infect cells of the monocyte-macrophage lineage to cause progressive degenerative diseases without clinical immunodeficiency. EIAV causes a uniquely dynamic disease that is characterized by recurrent disease episodes including fever, diarrhea, lethargy, anemia, and thrombocytopenia. Although EIAV provides an important animal model for lentivirus disease resulting from macrophage infection, to date there has been no definition of the specific cellular receptor(s) used by the equine lentivirus to infect target cells. In the current study, we have identified and cloned a functional receptor for EIAV, designated equine lentivirus receptor-1 (ELR1), related to the family of TNF receptor (TNFR) proteins. ELR1 was shown to be expressed in various equine cells permissive for EIAV replication in vitro, including monocytes and macrophages. In contrast, EIAV-resistant human, murine, and simian cells were negative for ELR1 expression but became susceptible to virus infection when transduced with a recombinant murine retrovirus expressing the ELR1. Thus, these results identify a specific functional receptor for a macrophagetropic lentivirus and indicate that infection by EIAV may be mediated by a single receptor, in contrast to coreceptors used by the lymphotropic immunodeficiency lentiviruses.

Amino Acid Sequence↗

PubMed2005

Dose-response relationship in locoregional control for patients with stage II-III esophageal cancer treated with concurrent chemotherapy and radiotherapy.

PURPOSE: To evaluate the correlation between radiation dose and locoregional control (LRC) for patients with Stage II-III unresectable esophageal cancer treated with concurrent chemotherapy and radiotherapy. METHODS AND MATERIALS: The medical records of 69 consecutive patients with clinical Stage II or III esophageal cancer treated with definitive chemoradiotherapy at the University of Texas M. D. Anderson Cancer Center between 1990 and 1998 were retrospectively reviewed. Of the 69 patients, 43 had received < or =51 Gy (lower dose group) and 26 >51 Gy (higher dose group). The median dose in the lower and higher dose groups was 30 Gy (range, 30-51 Gy) and 59.4 Gy (range, 54-64.8 Gy), respectively. Two fractionation schedules were used: rapid fractionation, delivering 30 Gy at 3 Gy/fraction within 2 weeks, and standard fractionation, delivering > or =45 Gy at 1.8-2 Gy/fraction daily. Total doses of <50 Gy were usually given with rapid fractionation. Cisplatin and 5-fluorouracil were administrated to 93% of the patients. RESULTS: The patient characteristic that differed between the two groups was that patients in the lower dose group were more likely to have had weight loss >5% (46.2% vs. 23.3%). The lower dose group had more N1 tumors, but the tumor classification and stage grouping were similar in the two groups. The median follow-up time for all patients was 22 months (range, 2-56 months). Patients in the higher dose group had a statistically significant better 3-year local control rate (36% vs. 19%, p = 0.011), disease-free survival rate (25% vs. 10%, p = 0.004), and overall survival rate (13% vs. 3%, p = 0.054). A trend toward a better distant-metastasis-free survival rate was noted in the higher dose group (72% vs. 59%, p = 0.12). The complete clinical response rate was significantly greater in the higher dose group (46% vs. 23%, p = 0.048). In both groups, the most common type of first failure was persistence of the primary tumor. Significantly fewer patients in the higher dose group had tumor persistence after treatment (p = 0.02). No statistically significant difference was found between the two groups in the pattern of locoregional or distant failure. The long-term side effects of chemoradiotherapy were similar in the two groups, although it was difficult to assess the side effects accurately in a retrospective fashion. On multivariate analysis, Stage II (vs. III) disease and radiation dose >51 Gy were independent predictors of improved LRC, and locoregional failure was an independent predictor of worse overall survival. CONCLUSION: Our data suggested a positive correlation between radiation dose and LRC in the population studied. A higher radiation dose was associated with increased LRC and survival in the dose range studied. The data also suggested that better LRC was associated with a lower rate of distant metastasis. A threshold of tumor response to radiation dose might be present, as suggested by the flattened slope in the high-dose area on the dose-response curve. A carefully designed dose-escalation study is required to confirm this assumption.

Adult↗

PubMed2005

Construction of a recombinant attenuated Salmonella typhimurium DNA vaccine carrying Helicobacter pylori hpaA.

AIM: To construct a recombinant attenuated Salmonella typhimurium DNA vaccine carrying Helicobacter pylori hpaA gene and to detect its immunogenicity. METHODS: Genomic DNA of the standard H pylori strain 17 874 was isolated as the template, hpaA gene fragment was amplified by polymerase chain reaction (PCR) and cloned into pUCmT vector. DNA sequence of the amplified hpaA gene was assayed, then cloned into the eukaryotic expression vector pIRES through enzyme digestion and ligation reactions. The recombinant plasmid was used to transform competent Escherichia coli DH5alpha, and the positive clones were screened by PCR and restriction enzyme digestion. Then, the recombinant pIRES-hpaA was used to transform LB5000 and the recombinant plasmid isolated from LB5000 was finally used to transform SL7207. After that, the recombinant strain was grown in vitro repeatedly. In order to identify the immunogenicity of the vaccine in vitro, the recombinant pIRES-hpaA was transfected to COS-7 cells using Lipofectamine2000, the immunogenicity of expressed HpaA protein was detected with SDS-PAGE and Western blot. RESULTS: The 750-base pair hpaA gene fragment was amplified from the genomic DNA and was consistent with the sequence of H pylori hpaA by sequence analysis. It was confirmed by PCR and restriction enzyme digestion that H pylori hpaA gene was inserted into the eukaryotic expression vector pIRES and a stable recombinant live attenuated Salmonella typhimurium DNA vaccine carrying H pylori hpaA gene was successfully constructed and the specific strip of HpaA expressed by pIRES-hpaA was detected through Western blot. CONCLUSION: The recombinant attenuated Salmonella typhimurium DNA vaccine strain expressing HpaA protein with immunogenicity can be constructed and it may be helpful for further investigating the immune action of DNA vaccine in vivo.

Adhesins, Bacterial↗

PubMed2005

Impact of personality and coping mechanisms on health related quality of life in liver transplantation recipients.

BACKGROUND: With the great development of liver transplantation in China, long survival and quality of life after liver transplantation have been matters of growing interest. This study was designed to investigate the impact of personality and coping skills on the quality of life after liver transplantation. METHODS: Fifty-five outpatients who had been followed up after liver transplantation at our center were assessed by general quality of life inventory (GQOLI-74), a medical coping modes questionnaire (MCMQ), an eysenck personality questionnaire (EPQ), and a general condition questionnaire(GCQ). RESULTS: The score for material well-being was the lowest(63.22+/-12.67) and for psychological well-being the highest(73.43+/-12.60) in 4 dimensions of the GQOLI in post transplantation patients. Their main coping method was confrontation (21.40+/-3.70). The main characteristics of their personality were extraversation (E score 12.96+/-4.13) and neuroticism (N score 8.20+/-4.90). The total score of the GQOLI was positively correlated with confrontation and E score, and it was negatively correlated with acceptance and N score. The physical well-being positively associated with the E score. The psychological well-being was positively correlated with confrontation and L score, and was negatively correlated with acceptance, P and N score. Social well-being was positively correlated with confrontation and E score, and was negatively correlated with acceptance and N score. Material well-being was not correlated with coping methods and personality. CONCLUSION: The quality of life in post liver transplantation patients is associated with their psychological characteristics.

Adaptation, Psychological↗

PubMed2005

[Soil enzyme activities of limestone degraded ecosystem at its different restoration phases].

The study showed that there was no distinct descending of enzyme activities along the soil profile of limestone degraded ecosystem, which were enhanced with progressive succession, and varied with vegetation characteristics, soil types, and soil enzyme properties. On the whole, soil enzyme activities enhanced in order of herb < Cupressuss funebris high forest< shrubbery, and under the same vegetation, limestone Cupressuss funebris high forest had higher soil enzyme activities than purple psammophytia. There was no significant correlation between soil enzyme activities and soil pH, while significant correlation was found between soil moisture content, soil total nitrogen content and soil enzyme activities, indicating that soil water and nutrient contents were the key factors of ecological restoration in this region. Different soil enzymes in the same vegetation-soil system as well as the same enzyme in the same soil type but at different restoration phases had different activities, so did for the same type vegetation but different soil type.

Alkaline Phosphatase↗

PubMed2005

[Cloning of Human canstatin gene and expression of its recombinant protein].

OBJECTIVE: To clone human canstatin gene and express its recombinant protein. METHODS: The total RNA was extracted from human placenta. The canstatin gene fragment was synthesized and amplified from the total RNA by RT-PCR. The resulting product was cloned into pUCm-T vector and transformed into E.coli DH5alpha through electroporation. The gene was sequenced by the Sanger Dideoxy-mediated chain-termination method, and then the canstatin cDNA was cloned into the BamHI and HindIII sites of plasmid pET-22b (+) and transformed into E.coli BL21 where it was induced to express proteins by isopropyl-1-thio-b-Dgalactopyranoside (IPTG). RESULTS: The extracted total RNA was separated into three clear bands indicating 28S, 18S, and 5S after electrophoresis. The canstatin gene fragment was synthesized and amplified from the total RNA by RT-PCR. The resulting products were cloned into pUCm-T vectors, and then were transformed into E.coli DHSa. After an over night culture, both blue and white colonies were found on the agar plate. Six white colonies were selected and cut by BamHI and HindIII. The plasmids DNA in one white colony showed one band near the location of primary plasmid after digested by BamHI and two bands near the locations of primary plasmid and objective gene fragment after digested by HindIII. The cloned gene in this white colony was sequenced and demonstrated to have the same sequence as that of canstatin gene in GenBank. Then canstatin cDNA was cut down from pUCm-T with BamHI and HindIII and ligated into the vector pET-22b (+). The resultant plasmid pET-22b (+)/canstatin was then transformed into E.coli BL21. White colonies were found on LB agar plate. Seven of them were selected and their plasmids were digested with both BamHI and HindIII. After electrophoresis, all selected colonies showed two specific bands, one was found near the location of primary plasmids, and the other near that of objective gene fragment. After IPTG induction, there was a new protein band about Mr 24 000 on SDS-PAGE. As estimated by densitometry, the percentage of the expressed product over total bacterial proteins was 18.2%, 18.8%, 23.0% and 23.4%, respectively, 1, 2, 3, and 4 hours after induction. CONCLUSION: Human canstatin gene was successfully cloned and its recombinant proteins were expressed in this study.

Base Sequence↗

PubMed2005

Impact of multidrug resistance 1 gene polymorphism on tacrolimus dose and concentration-to-dose ratio in Chinese liver transplantation recipients.

OBJECTIVE: To investigate whether the polymorphism of multidrug resistance 1 gene (MDR1) in the donors and liver transplantation recipients was correlated with interindividual variation in tacrolimus dose requirement and concentration-to-dose ratio. METHODS: The occurrence of MDR1 3435(C-->T) polymorphism was investigated by polymerase chain reaction followed by restriction fragment length polymorphism analysis in 50 liver transplant recipients and their corresponding donors. Doses (mg/kg body weight) and dose-adjusted trough levels (ng/mL per mg/kg body weight) were compared according to allelic status for MDR1. RESULTS: The MDR1 genotype CC was observed in 23 subjects (23%), whereas 64 (64%) were CT and 13 (13%) were TT. Tacrolimus doses required to achieve target blood concentrations were higher in the patients with MDR1 CC genotype than in the CT or TT genotype patients, and the dose-adjusted trough levels were lower. No significant differences were found in tacrolimus doses or dose-adjusted trough levels according to the donor's MDR1 genotype. CONCLUSION: Tacrolimus dose requirement and dose-adjusted trough levels were correlated with MDR1 3435 (C-->T) polymorphism, and MDR1 3435 (C-->T) polymorphism analysis is helpful to individualize tacrolimus administration.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

Esophagectomy after concurrent chemoradiotherapy improves locoregional control in clinical stage II or III esophageal cancer patients.

PURPOSE: To evaluate the effect of surgical resection on the outcome of patients with clinical Stage II or III cancer of the esophagus treated with concurrent chemoradiotherapy. METHODS AND MATERIALS: A retrospective review of 132 consecutive patients with clinical Stage II or III esophageal cancer treated with concurrent chemoradiotherapy between January 1990 and December 1998 was performed. Of the 132 patients, 60 underwent esophagectomy 6-8 weeks after chemoradiotherapy. The median radiation dose was 50 Gy (range, 30-64.8 Gy) in the definitive chemoradiation group and 45 Gy (range, 30-50.4 Gy) in the chemoradiation plus esophagectomy group. RESULTS: Statistically significant differences were found between the two groups in median age, histologic subtype, tumor location, and number of patients with T4 disease. Patients who underwent definitive chemoradiotherapy were older (p = 0.0004) and more likely to have squamous cell carcinoma than adenocarcinoma (p <0.000), upper thoracic or cervical esophageal tumors (p <0.000), and T4 tumors (p = 0.024). Patients treated with chemoradiation plus esophagectomy had statistically significant superior 5-year loco-regional control (67.1% vs. 22.1%, p <0.000), disease-free survival (40.7% vs. 9.9%, p < 0.000), and 5-year overall survival (52.6% vs. 6.5%, p < 0.000) rates and median survival time (62 vs. 12 months) compared with patients treated with chemoradiotherapy only. However, no statistically significant difference was found in the rate of distant metastasis-free survival between the two groups (67.5% vs. 65.8%, p = 0.3). Surgical resection of the tumor was an independent predictor of improved locoregional control and overall survival in both univariate and multivariate analyses. To reduce the effect of the selection bias on the outcome, 34 patients in each group with matched pretreatment characteristics were compared. The results showed statistically significant better overall survival, disease-free survival, and locoregional control in favor of the chemoradiotherapy plus esophagectomy group. No statistically significant difference in distant metastasis-free survival was found in this subgroup analysis. CONCLUSIONS: Locoregional control was better in clinical Stage II or III esophageal cancer patients treated with concurrent chemoradiation plus esophagectomy. An improvement in survival occurred in the chemoradiation plus esophagectomy group, although this observation may have reflected selection bias. The results from this study suggest the need for a randomized trial to compare chemoradiation with or without esophagectomy in the treatment of cancer of the esophagus.

Adenocarcinoma↗

PubMed2004

Induction chemotherapy improved outcomes of patients with resectable esophageal cancer who received chemoradiotherapy followed by surgery.

PURPOSE: To investigate the effect of induction chemotherapy (CHT) before trimodality therapy on the outcome of patients with resectable cancer of the esophagus. METHODS AND MATERIALS: This retrospective study included 81 consecutive patients with resectable cancer of the esophagus who received neoadjuvant chemoradiotherapy followed by esophagectomy between January 1990 and December 1998 (inclusive). Thirty-nine patients underwent chemoradiotherapy followed by esophagectomy (CHT/RT+S), 42 received additional induction CHT followed by CHT/RT+S (CHT+CHT/RT+S). Of the 81 patients, 47 were entered in institutional or national prospective trials (6 in the CHT/RT+S and 41 in the CHT+CHT/RT+S group). Induction CHT consisted of three courses of 5-fluorouracil (5-FU), cisplatin, and paclitaxel given in 28-day cycles in 37 patients (88.1%). Concurrent CHT was 5-FU and platinum based. The median radiation dose for patients treated with CHT/RT+S was 30 Gy (range, 30-50.4 Gy) delivered in a median of 10 fractions (range, 10-28 fractions) and 45 Gy (range, 30-45 Gy) in a median of 25 fractions (range, 10-25 fractions) for patients treated with CHT+CHT/RT+S. Esophagectomy was performed 6-8 weeks after completion of concurrent chemoradiotherapy. Most patients underwent transthoracic esophagectomy (n = 66, 82.5%). RESULTS: The pretreatment characteristics were well balanced between the two groups except for age. The median follow-up time was 29 months (22 months for the CHT/RT+S group and 38.5 months for the CHT+CHT/RT+S group) for all patients and 49 months for living patients. The actuarial overall survival (OS), disease-free survival (DFS), locoregional control (LRC), and distant metastasis-free survival (DMFS) rate at 5 years for the entire group was 46%, 36.6%, 70.7%, and 53.2%, respectively. Statistically significant differences in the OS, DFS, and LRC rates between the two groups were detected. Specifically, the 5-year OS rate was 22.8% and 71.1% in the CHT/RT+S and CHT+CHT/RT+S group (p = 0.0001), respectively. The 5-year DFS rate was 27.6% and 56.6% in the CHT/RT+S and CHT+CHT/RT+S group (p = 0.003), respectively. The 5-year LRC rate was 64.2% and 85.6% in the CHT/RT+S and CHT+CHT/RT+S group (p = 0.007), respectively. The difference in the DMFS rate between the two groups was statistically significant, with a 2- and 5-year actuarial rate of 63.9% and 51.9%, respectively, in the CHT/RT+S group and 76.9% and 74.1%, respectively, in the CHT+CHT/RT+S group (p = 0.04). The statistically significant differences persisted when patients who received >/=45 Gy in each group were compared. Among those patients, the 5-year OS, DFS, LRC, and DMFS rates were 23.1%, 15.4%, 58.6%, and 39.2%, respectively, for those receiving CHT/RT+S, and 71.4% (p = 0.001), 55.8% (p = 0.0008), 84.6% (p = 0.005), and 77.3% (p = 0.009), respectively, for those receiving CHT+CHT/RT+S. The pathologic complete response (pCR) rate was greater in the CHT+CHT/RT+S group compared with in the CHT/RT+S group (p = 0.008). In univariate analysis, young age, good Karnofsky performance status, Stage II disease, total radiation dose, multiple drug regimen for concurrent CHT, pCR, R0 resection, distant disease progression, and CHT+CHT/RT+S treatment proved to be prognostic factors for OS. Lower esophageal/gastroesophageal junction tumor location, pCR, R0 resection, and CHT+CHT/RT+S treatment were favorable prognostic factors for LRC. Neither the total radiation dose nor multiple drugs for concurrent CHT were negative prognostic factors for LRC. In multivariate analysis, pCR, R0 resection, and treatment with CHT+CHT/RT+S were independent positive predictive factors for OS, and distant recurrences were negative predictive factors for OS. R0 resection, CHT+CHT/RT+S treatment, and lower esophageal/gastroesophageal junction tumor location were positive predictive factors for LRC. The radiation dose was not identified as an independent prognostic factor for either OS or LRC in the multivariate analysis. Meaningful multivariate analysis could not be performed when the multiple drug vperformed when the multiple drug variable was included in the model because of the small number of patients. CONCLUSION: Significantly greater LRC, DFS, OS, and DMFS were found in patients treated with CHT+CHT/RT+S compared with those treated with CHT/RT+S. The pCR rate was significantly higher in the CHT+CHT/RT+S group. Induction CHT was an independent favorable prognostic factor for both LRC and OS for the population included in this study. Our data suggest that a randomized trial comparing CHT+CHT/RT+S and CHT/RT+S is warranted to assess further the merits of this treatment in patients with this currently very lethal cancer.

Adult↗

PubMed2004

Reversal of multidrug resistance of cancer through inhibition of P-glycoprotein by 5-bromotetrandrine.

PURPOSE: The present study aimed to evaluate the MDR reversal activity of bromotetrandrine (BrTet), a bromized derivative of tetrandrine (Tet), in vitro and in vivo. METHODS: Drug sensitivity was determined using the MTT assay. The in vivo effect of Tet was investigated using nude mice grafted with sensitive and resistant KB human epidermoid cancer cells. Doxorubicin (Dox) accumulation was analyzed by fluorospectrophotometry and the protein and mRNA levels of P-glycoprotein (P-gp) were determined by immunocytochemistry and RT-PCR, respectively. RESULTS: BrTet at 0.25, 0.5 and 1 micro M reversed Dox resistance in MDR human breast cancer MCF-7/Dox cells dose-dependently and its potency was greater than that of Tet at the same concentrations. BrTet reversed vincristine (VCR), Dox and paclitaxel resistance in MDR human oral epidermoid carcinoma KBv200 cells as well as innate VCR and Dox resistance in human hepatocellular carcinoma Bel(7402) cells. However, BrTet showed no effect on the IC(50) values of the above-mentioned anticancer drugs in sensitive MCF-7 and KB cells. No reversal effect of BrTet on the cytotoxicity of 5-fluorouracil and cisplatin, non-P-gp substrates, was observed. In nude mice bearing KBv200 xenografts on the left flank and KB xenografts on the right flank, i.p. injection of 5 mg/kg and 10 mg/kg BrTet significantly enhanced the antitumor activity of Dox against KBv200 xenografts with inhibitory rates of 33.0% and 39.2%, while Dox alone inhibited the growth of KBv200 xenografts by only 11.6%. No enhancement by BrTet was seen in KB xenografts. Moreover, BrTet at 5 mg/kg reversed paclitaxel resistance in KBv200 xenografts. Fluorospectrophotometric assay showed that BrTet significantly increased the intracellular accumulation of Dox in MCF-7/Dox cells in a dose-dependent manner. BrTet also inhibited the overexpression of P-gp in MCF-7/Dox cells, but had no effect on mdr1 expression. CONCLUSIONS: BrTet showed significant MDR reversal activity in vitro and in vivo. Its activity may be related to the inhibition of P-gp overexpression and the increase in intracellular accumulation of anticancer drugs. BrTet may be a promising MDR modulator for eventual assessment in the clinic.

ATP Binding Cassette Transporter, Subfamily B, Mem↗