OBJECTIVEUnder various drought conditions and nitrogen application, the content of vindoline, catharanthine, vincristine and vinblastine in the leaf of Catharanthus roseus were illustrated to improve the content of alkaloid theoretically.

METHODSix groups were set in the experiment, which included: CK (natural control), CN (natural control + nitrogen), LK (low drought), LN (low drought + nitrogen), HK (high drought), HN (high drought + nitrogen) to discuss the change characteristics of total nitrogen, the activity of alkaline POD and TDC, the content of four alkaloids under the different conditions were measured.

RESULTUnder LK condition, the activity of POD, TDC were enhanced. In the early stage of stress (0-21 d), vindoline, catharanthine, vincristine and vinblastine accumulated, and reduced in the later stage (28-35 d). For all groups, adding exogenous nitrogen could improve the total content of nitrogen, vindoline and vinblastine, meanwhile the activity of POD and TDC were enhanced as well. The LN, HN treatments were beneficial to accumulating catharanthine and vinblastine.

CONCLUSIONDrought stress or additional nitrogen have an influence on both of the activities of POD and TDC, and the four alkaloids were affected as well. Thereinto, the LN condition was the most effective treatment for accumulating the four alkaloids (vindoline, catharanthine, vincristine and vinblastine), which were regulated by improve nitrogen content and enzymatic activity.

Catharanthus ; metabolism ; Nitrogen ; metabolism ; Peroxidase ; metabolism ; Stress, Physiological ; Vinblastine ; analogs & derivatives ; metabolism ; Vinca Alkaloids ; metabolism ; Vincristine ; metabolism ; Water ; metabolism

Aged ; Antineoplastic Agents, Phytogenic ; adverse effects ; Extravasation of Diagnostic and Therapeutic Materials ; therapy ; Humans ; Male ; Negative-Pressure Wound Therapy ; methods ; Vinblastine ; adverse effects ; analogs & derivatives

In this paper, the fluorogenic property of vindoline was exploited and, as a probe, used to analyze the interaction of vindoline with HSA by fluorescence and absorption spectra in combination with molecular modeling under a simulated physiological conditions. The evidences from synchronous fluorescence and absorption spectroscopes showed the effect of vindoline on the microenvironment around HSA in aqueous solution. Data obtained by the fluorescence spectroscopy indicated that binding of vindoline with HSA leads to dramatic enhancement of the fluorescence emission intensity. The binding constants and the number of binding sites between vindoline and HSA at different temperatures (303, 310 and 317 K) were calculated according to the data obtained from fluorescence titration. Molecular docking was performed to reveal the possible binding mode or mechanism and suggested that vindoline can bind strongly to HSA. It is considered that vindoline binds to HSA mainly by a hydrophobic interaction and there are four hydrogen bonds interactions between the drug and the residues Ala291, Arg222, Arg218 and Lys195, separately. Fluorescent displacement measurements confirmed that vindoline bind HSA on site II. The thermodynamic parameters obtained (the enthalpy change deltaH0 and the entropy change deltaS0 were calculated to be -10.30 kJ x mol(-1) and 79.98 J x mol(-1) x K(-1), respectively, according to the Van't Hoff equation) suggested that hydrophobic and electrostatic interaction is the predominant intermolecular forces stabilizing the complex.
Antineoplastic Agents, Phytogenic ; metabolism ; Binding Sites ; Computer Simulation ; Humans ; Protein Binding ; Serum Albumin ; chemistry ; metabolism ; Spectrometry, Fluorescence ; Spectrophotometry, Ultraviolet ; Thermodynamics ; Vinblastine ; analogs & derivatives ; metabolism

This study was purposed to explore the Rituximab (RTX)-mediated sensitization of B-NHL cell lines to apoptosis induced by Gemcitabine or Navelbine and its possible mechanism. The inhibitory rate of B-NHL cell proliferation was detected by XTT method, the IC₅₀ from Gemcitabine or Navelbine and combination of Gemcitabine or Navelbine with RTX was compared. The expression level of antiapoptotic protein BCL-2 in Daudi, Ramos, Raji and Namalwa cells treated with RTX of 20 μg/ml for 24 hours was detected by Western blot. The results showed that the RTX as a single agent could weakly induce the apoptosis of Daudi, Namalwa, Raji and Ramos lymphoma cell lines, the inhibiting rate of cell proliferation ranged from 3% to 10%; RTX could sensitize significantly the cytotoxity of Gemcitabine or Navelbine in Daudi, Namalwa and Raji cell lines; The expression of BCL-2 in Raji and Namalwa cell lines treated with RTX of 20 microg/ml for 24 hours was down-regulated. It is concluded that RTX can sensitize the cytotoxicity of Gemcitabine or Navelbine to the human lymphoma cell lines which displayed the synergistic effect on Daudi, Namalwa and Raji cell lines. The BCL-2 expression level in Raji and Namalwa cell lines treated by RTX is down-regulated which may be one of the mechanisms sensitizing the cytotoxicity of Gemcitabine or Navelbine.
Antibodies, Monoclonal, Murine-Derived ; pharmacology ; Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; drug effects ; Cytotoxicity, Immunologic ; drug effects ; Deoxycytidine ; analogs & derivatives ; pharmacology ; Humans ; Lymphoma, T-Cell ; Proto-Oncogene Proteins c-bcl-2 ; Rituximab ; Vinblastine ; analogs & derivatives ; pharmacology

Anthracyclines ; pharmacology ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; Cisplatin ; administration & dosage ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Drug Resistance, Neoplasm ; Female ; Humans ; Taxoids ; administration & dosage ; Vinblastine ; administration & dosage ; analogs & derivatives

Catharanthus roseus (L.) G. Don is a plant of the Catharanthus genus of Apocynaceae which has been reported to have therapeutic effects of detoxication and anticancer. In order to further study the alkaloid constituents of C. roseus, the aerial parts of the plant were extracted with 95% EtOH, and then treated with 2% H2SO4 and NH3H2O to obtain total alkaloids. The total alkaloids were separated and purified by column chromatography over silica gel and prepared by high performance liquid chromatography (HPLC). Their structures were elucidated on the basis of physicochemical properties and spectral data. A new alkaloid together with five known compounds were isolated and identified as vindolinine B (1), lochnericine (2), horhammericine (3), vindorosine (4), vindoline (5), and coronaridine (6). Compound 1 is a new compound and named as vindolinine B.
Antineoplastic Agents, Phytogenic ; chemistry ; isolation & purification ; Catharanthus ; chemistry ; Ibogaine ; analogs & derivatives ; chemistry ; isolation & purification ; Indole Alkaloids ; chemistry ; isolation & purification ; Molecular Structure ; Plant Components, Aerial ; chemistry ; Plants, Medicinal ; chemistry ; Vinblastine ; analogs & derivatives ; chemistry ; isolation & purification

We think the strategy of classic natural product-based drug discovery will be an effective way for us to develop new drugs with independent intellectual property. The strategy includes: to study the molecular mechanism of action of classic natural product with chemical genetics and chemical biology approaches firstly; then establish the proper in vitro bioassay or bioassay system based on its molecular mechanism for their pharmacodynamic evaluation; finally, study their structure-activity, structure-toxicity and structure-ADME properties with medicinal chemistry.
Animals ; Anti-HIV Agents ; chemical synthesis ; pharmacology ; Antineoplastic Agents, Phytogenic ; chemical synthesis ; pharmacology ; Berberine ; analogs & derivatives ; chemical synthesis ; pharmacology ; Biological Products ; chemical synthesis ; chemistry ; pharmacology ; Camptothecin ; analogs & derivatives ; chemical synthesis ; pharmacology ; Drug Discovery ; Humans ; Hypoglycemic Agents ; chemical synthesis ; pharmacology ; Oleanolic Acid ; analogs & derivatives ; chemical synthesis ; pharmacology ; Triterpenes ; chemical synthesis ; pharmacology ; Vinblastine ; analogs & derivatives ; chemical synthesis ; pharmacology

OBJECTIVETo identify predictive markers of the long-term outcome for neo-adjuvant chemotherapy (NC) in locally advanced breast cancer (LABC) treated with intravenous vinorelbine (V) and epirubicin (E) combination regimen.

METHODSOne hundred and nineteen patients with LABC were treated from September 2001 to May 2006. All patients were diagnosed as invasive breast cancer by 14G core needle biopsy and treated with three cycles of VE regimen before the operation. The patients were subjected to surgery and subsequently were given other three cycles of VE or cyclophosphamide+epirubicin+fluorouracil (CEF) regimen according to the clinical responses. Local-regional radiotherapy was applied to all patients after the chemotherapy and followed by hormone-therapy according to hormone receptor status. The impact of clinical, pathological, and immunohistochemical features on disease free survival (DFS) and overall survival (OS) was evaluated.

RESULTSAll patients were evaluable for responses: clinical complete response was documented in 27 patients (22.7%), 78 patients (65.5%) obtained partial clinical response. The pathological complete response was found in 22 cases (18.5%). Of the patients, 115 cases (96.6%) were followed-up for a median time of 63.4 months (range, 9-76 months), the 5-year DFS rate and OS rate was 58.7% and 71.3%, respectively. On multivariate analysis, high pre-Ki-67 (P=0.012) and post-Ki-67 expression (P=0.045), no pathological complete response after NC (P=0.034) were associated with the higher risk of disease relapse; high pre-Ki-67 (P=0.017) and post-Ki-67 expression (P=0.001), negative pre-ER (P=0.002) and no pathological complete response after NC (P=0.034) were associated with a shorter survival.

CONCLUSIONPathological response in primary tumor, pre-Ki-67 and post-Ki-67 expression, pre-ER expression are important predictors of long-term outcome for LABC patients with three cycles of VE regimen before operation.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; surgery ; Chemotherapy, Adjuvant ; Epirubicin ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Vinblastine ; administration & dosage ; analogs & derivatives

OBJECTIVETo characterize the clinical features of desmoid tumor, assess the efficacy of conservative chemotherapy for inoperable desmoid tumor and analyze the prognostic factors.

METHODSFrom August 2009 to December 2013, 52 patients with inoperable desmoid tumor were treated in our department and received chemotherapy with vinorelbine combined with low-dose methotrexate. The clinical data of the patients were analyzed retrospectively.

RESULTSThe patients studied included 22 male and 30 female patients with the age of disease onset ranging from 2 to 46 years (mean 18.7 years). The lesions occurred most frequently in the lower limbs (36.5%, 19/52) and the tumor size ranged from 2.7 to 37 cm (mean 9.5 cm). The patients were followed up for a median of 29 months (7 to 64 months). The chemotherapy lasted for 4 to 30 months (median 12 months). After completion of the chemotherapy, 1 patient had a complete response (CR), 18 showed partial responses (PR), 27 cases had stable disease (SD), and 6 had progressive disease (PD), with an overall response rate (ORR) of 88.5%. The progression-free survival (PFS) time of the patients ranged from 4 to 63 months (median 26.5 months) with a 2-year PFS rate of 76.7% and 5-year PFS rate of 41.9%. A longer chemotherapy duration (over 12 months) was associated with a more favorable prognosis. No significant differences in PFS were found between the patients stratified by gender, age of disease onset, age when receiving chemotherapy, tumor site, or tumor size.

CONCLUSIONFor recurrent, inoperable and progressive desmoid tumor, long enough cycles of vinorelbine combined with low-dose methotrexate can be an effective and safe option for tumor control.

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; Fibromatosis, Aggressive ; drug therapy ; Humans ; Male ; Methotrexate ; administration & dosage ; therapeutic use ; Middle Aged ; Prognosis ; Retrospective Studies ; Vinblastine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Young Adult

OBJECTIVEThis study was conducted to investigate the correlation between anemia and postoperative chemotherapy in elderly cancer patients.

METHODSOne hundred and fifty-seven elderly patients ( age ≥ 60) with pathologically confirmed breast, lung and digestive tract cancers, who had HGB ≥ 120 g/L and ECOG scores 0-2, were included in this study. We reviewed their clinicopathological data and analyzed the correlation of anemia in breast cancer patients after 1, 3 or 5 cycles and lung cancer patients after 1, 2 or 3 cycles of postoperative chemotherapy.

RESULTSAmong the 157 cases, the overall proportion of anemia was 31.8% (50/157) , with 18.8% in male and 47.2% in female patients (P < 0.001). After three cycles of chemotherapy, the proportion of anemia was 57.9% in lung cancer, 34.5% in breast cancer, 26.3% in gastric cancer and 9.3% in colorectal cancer patients (P < 0.001). The proportion of anemia during 5 cycles chemotherapy (three cycles in lung cancer) was gradually increasing. In the lung cancer patients, anemia was observed in 66.7% of patients who received vinorelbine plus cispiatin regimen and 25.0% of cases who received vinorelbine regimen chemotherapy (P = 0.044).

CONCLUSIONSIn most elderly patients with normal hemoglobin level and in good conditions, the chemotherapy-related anemia is mild and less frequent. Age should not limit the adjuvant chemotherapy in elderly cancer patients. Attention should be paid to the possibility of anemia in elderly female lung cancer patients receiving multiple cycle platinum-based chemotherapy regimens.

Aged ; Anemia ; chemically induced ; epidemiology ; Antineoplastic Agents ; adverse effects ; Breast Neoplasms ; drug therapy ; Chemotherapy, Adjuvant ; Cisplatin ; adverse effects ; Colorectal Neoplasms ; drug therapy ; Female ; Humans ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Stomach Neoplasms ; drug therapy ; Vinblastine ; adverse effects ; analogs & derivatives