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Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd
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Objective To conduct the in vitro study on the changes of gene and biological characteristics of different esophageal interstitial fibroblasts after their indirect contact wish esophageal cancer cell lines.Methods The mRNA levels of Vimentin,α-SMA,TGF-β1,HGF,MMP2 and MMP9 in normal esophageal interstitial fibroblasts(NFs),atypical hyperplasia interstitial fibroblasts(AFs) and cancer related fibroblasts(CAFs) and PCNA mRNA in esophageal carcinoma cell line were detected after their indirectly mutual contact.The invasion test of carcinoma cell line was conducted.Results From NFs,AFs to CAFs,the expression of Vimentin mRNA had no difference.The mRNA expressions of α-SMA,TGF-β1,HGF,MMP2 and MMP9 were gradually increased.After indirectly mutual contact with esophageal carcinoma cell line,the mRNA expressions of α-SMA,TGF-β1,HGF,MMP2 and MMP9 in NFs and AFs were up-regulated,and the difference was statistically significant(P＜0.05),while the related mRNA expression in CAFs had no obvious change.The expression of PCNA mRNA in esophageal carcinoma cell line had no change after contact with NFs,but the expression of PCNA mRNA was significantly up-regulated after interaction with AFs contacting with CAFs.Conclusion The esophageal carcinoma cells and esophageal interstitial fibroblasts could affect the proliferation activity and invasive characteristics of counterparts.
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Objective To investigate the expressions ofα‐SMA in different esophageal stromal fibroblasts in esophageal car‐cinogenesis .Methods IHC method was uesd to detect the expression of α‐SMA protein in stromal fibroblasts of twenty normal e‐sophageal tissues ,eighty precancerous lesions and fifty esophageal carcinomas respectively .Three kinds of esophageal stromal fibro‐blasts were cultured primarily and cells immunohistochemical staining was carrired out after being purified .Expression of α‐SMA was detected by RT PCR .Results IHC results showed thatα‐SMA expressions in normal ,precancerous and cancerous lesions were of significant differences .RT‐PCR results showed thatα‐SMA expressions were different significantly among three kinds of fibro‐blasts .Conclusion Esophageal stromal fibroblasts were activated with carcinogenensis .AFs was possibly the origion of CAFs .
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Objective To establish a method for simultaneous determination of contents of schisandrin B, schisantherin A, lobetyolin and ruscogenin in Huangqi Shengmai Decoction with HPLC method. Methods The chromatographic column was an Agilent Eclipse C18 column (4.6 mm × 250 mm, 5 μm) that was maintained at a constant temperature of 30 ℃. The mobile phase was 0.1% acetic acid solution-acetonitrile, with gradient elution. The flow rate was 1.0 mL/min. The detection was at wavelength of 280 nm. Results The standard curves of schisandrin B, schisantherin A, lobetyolin and ruscogenin had good linearity in the ranges of 0.862 5-21.562 5μg (r 2=0.999 1), 0.737 5-18.437 5μg (r 2=0.999 4), 0.095 2-2.380 0 μg (r 2=0.999 6), and 0.810 0-20.250 0 μg (r 2=0.999 0), respectively. The average recoveries of the four components were 98.06%(RSD=1.64%), 99.61%(RSD=2.72%), 97.98%(RSD=1.45%), and 99.30%(RSD=1.25%), respectively. Conclusion This method is accurate, rapid and specific, achieving the stable results with high reproducibility.
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<p><b>OBJECTIVE</b>To investigate the possibility and short-term effect of high dose chemotherapy with peripheral blood stem cell support in the preoperative therapy of breast cancer, and-its influence on the following operation and would healing.</p><p><b>METHODS</b>Three patients with T(3)N(1)M(0) (III(a)), T(4)N(1)M(0) (III(b)), T(4)N(1)M(1) (IV) of breast cancer were diagnosed histopathologically. After receiving HDC/APBSCT, the 3 patients were operated on. HDC/APBSCT process included 2 cycles of FEC induction chemotherapy; PBSC mobilization, APBSC collection and cryopreservation and PBSC infusion; and high-dose chemotherapy, APBSC infusion and supportive therapy. The therapy consisted of CTX2.5 g/m(2), VP-16 600 mg/m(2), and cerboplatin 600 mg/m(2) delivered on day 1, APBSC infusion 48 h later, rhG-CSF (150 microg, BID) was administered 4 h after infusion of APBSC until WBC was higher than 10 x 10(9)/L. During HDC/APBSCT, the patients were protected in the air laminar flow room with supportive therapy of antibiotics, anti-virus and anti-fungus drugs. They left the air laminar flow room after their WBC was greater than 2 x 10(9)/L. Case 1 was treated by radical mastectomy, Case 2 by improved radical mastectomy, Case 3 by improved radical mastectomy and transplantation of skin for the large area.</p><p><b>RESULTS</b>Rapid recovery of bone marrow function was observed in all 3 patients. Operation was performed 4 weeks after HDC/PBSCT in Cases 1, 2 and 33 days in Case 3. No influence was seen on operative procedure and would healing, especially in Case 3 with a large area of skin transplantation. Two patients with stage III(a) and III(b) have been alive since the treatment for 30 months and the other with stage IV died of brain metastasis 16 months later.</p><p><b>CONCLUSIONS</b>HDC/APBSCT as a preoperative therapy for breast cancer has no influence on the coming surgery and would healing, even on skin transplantation for a large area. It has a practical response in stage III(a) and III(b), but it is still controversial in stage IV. This method as a salvage therapy for patients with breast cancer of intemuediate or stage.</p>
Subject(s)
Adult , Female , Humans , Middle Aged , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Breast Neoplasms , Therapeutics , Combined Modality Therapy , Hematopoietic Stem Cell Transplantation , Mastectomy, Radical , Neoplasm Staging , Preoperative Care , Salvage TherapyABSTRACT
<p><b>BACKGROUND</b>To evaluate the reversal effect of high dose tamoxifen on multidrug resistance to EP regimen in patients with non-small cell lung cancer.</p><p><b>METHODS</b>A total of 41 patients with NSCLC were studied, who were resistant to EP regimen and were proved to have P-gp protein overexpression. All patients were randomizedly divided into two arms. Reversal group (n=21) received oral tamoxifen 100?mg, 2 times everyday on D1-5, together with EP regimen. Control group (n=20) were only given EP regimen.</p><p><b>RESULTS</b>In reversal group, complete response occurred in 1 patient, and partial response in 5; disease remained stable in 11 patients, and tumor progression occurred in 4 patients. The response rate was 28.6%(6/21). In control group, no response occurred; 9 patients had stable diseases, and the other 11 progressed. There was a significant difference in response rate between the two groups (P=0.012?1). In reversal and control groups, the median survivals were 8.4 and 4.6 months respectively (P < 0.01), and 1-year survial rates were 38.1% and 35.0% respectively. Reversal of P-gp occurred in 7 cases of reversal group (33.3%),and none in control group (P= 0.005?2) . There was no significant difference in toxicities between the two groups (P > 0.05).</p><p><b>CONCLUSIONS</b>High dose tamoxifen can remarkably downregulate the expression of P-gp and partially reverse the multidrug resistance to EP regimen for non-small cell lung cancer.</p>
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Purpose:Clinical research has been done to show whether continuous infusion of navelbine can increase curative effect and decrease toxicity.Methods:Patients studied were non operable NSCLC and recurrent or metastatic breast cancer. Navelbine is given through a catheter in the venae subclavia by continuous infusion for 24 hours. Regimen:NVB 10 mg/iv/day 1+NVB 10 mg/iv continuous infusion 24 h/day 1—5+DDP 40 mg/iv 2h/day 1—3+Gransetron 3 mg/iv day1,3,5 given every 21 days. Results:Among 47 patients 35 patients were NSCLC and 12 patients were breast cancer. Average age was 58.9 years. Of the NSCLC patients, 12 were squamous cell carcinoma and 23 patients were adenocarcinoma; two patients were stage Ⅱ and 19 patients stage Ⅲ, 19 patients stage Ⅳ. All of the breast cancer cases were infiltrative duct carcinoma. Three patients were stage Ⅱ and nine patients were stage Ⅳ. Of the 47 patients, 44 patients were evaluable for response and 47 patients for toxicity. Response rate of NSCLC was 57%(19 pr) and breast cancer 63% (1 cr, 6 pr). Main toxicity was granulocytopenia and vomiting. WHO Ⅲ—Ⅳ grade granulocytopenia was 40% and vomiting 6.4%. Peripheral nerves toxicity was mild and only 6.4% patients had WHO I grade peripheral sensory nerve damage. No patients had severe nerve toxicity such as enteroplegia.Conclusions:Comparison of continuous infusion Navelbine and Cisplatin with classic usage of navelbine for management of NSCLC and breast cancer showed increased response rate and decreased toxicity. Administration through catheter venae subclavia can avoid chemo phlebitis. [