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Magyar Onkologia Dec 2017The present review about the history of anticancer drug research in Hungary intends to call attention to the importance of studies on their mode of action. Several lines... (Review)
Review
The present review about the history of anticancer drug research in Hungary intends to call attention to the importance of studies on their mode of action. Several lines of evidence suggest that clinically usable oncopharmacological properties could be revealed by this way. Among the numerous compounds certain alkylating sugar alcohols and 2'-deoxyuridine derivatives were submitted to detailed investigations concerning their mode of action. Myelobromol with selective action on the myeloid elements of bone marrow has been justified for its application in chronic myeloid leukemia therapy and also in bone marrow ablation before transplantation. Mitolactol is able to cross bloodbrain barrier, consequently could control certain brain tumors. 5-etil-2'-deoxyuridine by reducing dihydropyrimidine dehydrogenase activity is able to increase 5-fluorouracil concentration in the blood, resulting in improved antitumor effect. In contrast, 5-hexil-2'-deoxyuridine, as an inhibitor of glycoconjugate pathway by reducing heparan sulfate production, has the ability to prevent metastasis. Noteworthy, the remarkable effects of vinca alkaloids, antiestrogens, and GNRH analogues were also presented in this review.
Topics: Antineoplastic Agents, Alkylating; Databases, Factual; Drug Design; Forecasting; Humans; Hungary; Mannomustine; Mitobronitol; Mitolactol; Pharmaceutical Research; Pharmacology, Clinical; Quality Improvement; Retrospective Studies
PubMed: 29257158
DOI: No ID Found -
Oncotarget Oct 2016Different chemotherapy drugs are generally introduced in clinical practices combining with therapy for glioma treatment. However, these chemotherapy drugs have rarely... (Meta-Analysis)
Meta-Analysis
A network meta-analysis: the overall and progression-free survival of glioma patients treated by different chemotherapeutic interventions combined with radiation therapy (RT).
Different chemotherapy drugs are generally introduced in clinical practices combining with therapy for glioma treatment. However, these chemotherapy drugs have rarely been compared with each other and the optimum drug still remains to be proved. In this research, medical databases were consulted, PubMed, Embase and Cochrane Library included. As primary outcomes, hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS) with their corresponding 95% credential intervals (CrI) were reported. A network meta-analysis was conducted; the surface under the cumulative ranking curve (SUCRA) was utilized for treatment rank and a cluster analysis based on SUCRA values was performed. This research includes 14 trials with 3,681 subjects and eight interventions. In terms of network meta-analysis, placebo was proved to be inferior to the combination of temozolomide (TMZ), nimustine (ACNU) and cisplatin (CDDP). Also, bevacizumab (BEV) in conjunction with TMZ were significantly more effective than placebo with an HR of 0.40. The estimated probabilities from SUCRA verified the above outcomes, confirming that the combination of TMZ, ACNU and CDDP exhibited the highest ranking probability of 0.889 with respect to OS, while BEV in combination with TMZ - with a probability of 0.772 - ranked the first place with respect to PFS. According to the results of this network meta-analysis, the combination of (1) TMZ, ACNU and CDDP; (2) BEV in combination with TMZ and (3) cilengitide in combination with TMZ, are considered as the preferable choices of chemotherapy drugs for glioma treatment.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Bayes Theorem; Bevacizumab; Brain Neoplasms; Chemoradiotherapy; Cisplatin; Dacarbazine; Disease-Free Survival; Eflornithine; Glioma; Humans; Mitolactol; Network Meta-Analysis; Nimustine; Probability; Randomized Controlled Trials as Topic; Snake Venoms; Temozolomide; Treatment Outcome; Vincristine
PubMed: 27458167
DOI: 10.18632/oncotarget.10763 -
Gan To Kagaku Ryoho. Cancer &... Aug 2012The patient was a 48-year-old male with a right subclavicular tumor. The pathological diagnosis showed primitive neuroectodermal tumor(PNET)because of the rosette...
The patient was a 48-year-old male with a right subclavicular tumor. The pathological diagnosis showed primitive neuroectodermal tumor(PNET)because of the rosette formation and the positive neurogenic marker.Radiation was administered at a total dose of 50 Gy, because surgical resection would induce the loss of right arm function. CT examination demonstrated a reduction of the primary tumor and new multiple lung metastases. The patient received intravenous AI regimen(ADM and IFM). After the 7th course, both the primary tumor and multiple lung metastases decreased. AI regimen might be effective for PNET.
Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Boronic Acids; Bortezomib; Doxorubicin; Head and Neck Neoplasms; Humans; Lung Neoplasms; Male; Melphalan; Middle Aged; Mitolactol; Mitomycins; Neuroectodermal Tumors, Primitive; Pyrazines; Salvage Therapy; Suicide; Tomography, X-Ray Computed
PubMed: 22902461
DOI: No ID Found -
Cancer Metastasis Reviews Dec 2010The authors compared N0 with N+ cases in neoadjuvant chemotherapy regression and recurrence. During a 12-year period, 180 consecutive oral squamous cell cancer patients... (Review)
Review
The authors compared N0 with N+ cases in neoadjuvant chemotherapy regression and recurrence. During a 12-year period, 180 consecutive oral squamous cell cancer patients were observed. Of these patients, 78 were N0 and 102 N+ stages. The drugs used were as follows: bleomycin, vincristine, methotrexate, and mitolactol. After three courses of chemotherapy, the regression (complete response (CR), partial response (PR), and no response (NR)) and side effect rate were determined. All patients were operated on and observed for the number and localization of recurrences during 3 year follow-up time. The N0 cases came from T2-3, while N+ was from T2-4a (AJCC 2002). The regression in the N0 group was CR 46%, PR 53%, and NR 1%; but in the N+ group, it was CR 12%, PR 72%, and NR 16%. The regression rate was significantly higher (p = 0.00025) for N0 group than N+ group. The regression rate for T3 N0 was significantly higher (p = 0.055) than for T3 N+ cases. In the N0 stage, the regression rate was significantly higher (p = 0.0174) for T2 than T3. In N+ stage, there was no significant difference (p = 0.183) for T2-4a. The side effects were slight. The recurrence rate for the N0 group was significantly lower (15%, p = 0.000069), while for N+ group, it was 59%. The dependence in the T3 cases was also significant (p = 0.009) in the 3-year tumor-free survival. The N stage seems a more important prognostic factor for chemotherapy response and recurrence rate than the T stage. Stage III can be divided into subgroups without metastasis (III.a) and with metastasis (III.b.), based on significant difference in regression and recurrence rate.
Topics: Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Mouth Neoplasms; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Remission Induction
PubMed: 20842409
DOI: 10.1007/s10555-010-9259-7 -
Journal of Neuro-oncology Oct 2010To report long-term results for children with low-grade hypothalamic/chiasmatic gliomas treated on a phase II chemotherapy protocol. Between 1984 and 1992, 33 children...
To report long-term results for children with low-grade hypothalamic/chiasmatic gliomas treated on a phase II chemotherapy protocol. Between 1984 and 1992, 33 children with hypothalamic/chiasmatic LGGs received TPDCV chemotherapy on a phase II prospective trial. Median age was 3.0 years (range 0.3-16.2). Twelve patients (36%) underwent STRs, 14 (42%) biopsy only, and seven (21%) no surgery. Twenty patients (61%) had pathologic JPAs, nine (27%) grade II gliomas, and four (12%) no surgical sampling. Median f/u for surviving patients was 15.2 years (range 5.3-20.7); 20 of the 23 surviving patients had 14 or more years of follow-up. Fifteen-year PFS and OS were 23.4 and 71.2%, respectively. Twenty-five patients progressed, of whom 13 are NED, two are AWD, and 10 have died. All children who died were diagnosed and first treated at age three or younger. Age at diagnosis was significantly associated with relapse and survival (P = 0.004 for PFS and P = 0.037 for OS). No PFS or OS benefit was seen with STR versus biopsy/no sampling (P = 0.58 for PFS, P = 0.59 for OS). For patients with JPAs and WHO grade II tumors, the 15-year PFS was 18.8 and 22.2% (P = 0.95) and 15-year OS was 73.7 and 55.6% (P = 0.17), respectively. Upfront TPDCV for children with hypothalamic/chiasmatic LGGs resulted in 15-year OS of 71.2% and 15-year PFS of 23.4%. No survival benefit is demonstrated for greater extent of resection. Age is a significant prognostic factor for progression and survival.
Topics: Adolescent; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Disease Progression; Disease-Free Survival; Female; Glioma; Humans; Hypothalamic Neoplasms; Infant; Lomustine; Longitudinal Studies; Male; Mitolactol; Predictive Value of Tests; Procarbazine; Retrospective Studies; Salvage Therapy; Thioguanine; Treatment Outcome; Vincristine
PubMed: 20221671
DOI: 10.1007/s11060-010-0151-7 -
Chinese Medical Journal Nov 2009Both survivin and lung resistance related protein (LRP) are related to the chemoresistances in hepatocellular carcinoma (HCC). But the relationship between survivin and...
BACKGROUND
Both survivin and lung resistance related protein (LRP) are related to the chemoresistances in hepatocellular carcinoma (HCC). But the relationship between survivin and LRP is indefinite. The aim of this study was to investigate the effects of down-regulation of survivin on LRP expressions and the reversal of chemoresistances in HCC both in vitro and in vivo.
METHODS
The expressions of survivin were detected by RT-PCR and Western blotting in HCC cell line SMMC-7721 and SMMC-7721/ADM. The sensitivities of these two cell lines to ADM were evaluated by MTT assays. SiRNA which targeted survivin was transfected into SMMC-7721/ADM cells, then the sensitivity of SMMC-7721/ADM cells to ADM and the expressions of survivin and LRP were detected respectively. SMMC-7721/ADM cells were transplanted subcutaneously into nude mice to establish xenograft tumors. Antitumor activities of RNA interference (RNAi) targeting survivin, various doses of ADM and combination therapies were observed respectively. Possible toxicities were evaluated. LRP expression changes were tested. Student's t test was used for evaluating statistical significance.
RESULTS
The expressions of survivin in SMMC-7721/ADM cell line showed significant elevation compared to those in SMMC-7721 cell line (P < 0.05). Positive siRNA down-regulated the expressions of survivin significantly (P < 0.05). SiRNA targeting survivin could sensitize SMMC-7721/ADM cells to ADM and down-regulate the expressions of LRP significantly (P < 0.05). Growths of the tumors were significantly inhibited in positive siRNA group as compared with those in the control group from the 8th day (P < 0.05). Combination therapies caused significant tumor inhibitions compared with tumors of nude mice in the other three groups respectively (P < 0.05). No toxicities were found in nude mice treated by siRNA and combination therapies. The expressions of LRP were markedly reduced in tumors treated with siRNA targeting survivin (P < 0.05).
CONCLUSIONS
Down regulation of survivin gene by RNAi can increase chemosensitivity of HCC both in vitro and in vivo. The reversal of drug resistance may be reduced through the inhibitions of LRP.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Blotting, Western; Carcinoma, Hepatocellular; Cell Line, Tumor; Doxorubicin; Drug Resistance, Neoplasm; Humans; Inhibitor of Apoptosis Proteins; Mice; Mice, Inbred BALB C; Mice, Nude; Microtubule-Associated Proteins; Mitolactol; Mitomycins; RNA Interference; RNA, Small Interfering; Reverse Transcriptase Polymerase Chain Reaction; Survivin; Vault Ribonucleoprotein Particles; Xenograft Model Antitumor Assays
PubMed: 19951584
DOI: No ID Found -
Pathology Oncology Research : POR Jun 2010The purpose of this clinicopathological study was to evaluate the effects and efficiency of combined neoadjuvant chemotherapy related to surgical margin. 100... (Clinical Trial)
Clinical Trial
The purpose of this clinicopathological study was to evaluate the effects and efficiency of combined neoadjuvant chemotherapy related to surgical margin. 100 consecutively treated squamous cell cancer patients receiving a combined neoadjuvant therapy were selected (Bleomycin-Vincristin-Methotrexate (BVM) or BVM + Mitolactol or BVM + Cisplatin). After three courses of chemotherapy, the patients were operated on. The largest diameter of the primary tumors was compared before and after chemotherapy. In the surgical specimen, the involvement of surgical margin was assessed. The largest diameter before chemotherapy was: T2 30%; T3 55%; T4A 15%. After chemotherapy, the rest tumor was assessed in the surgical specimen as: no rest 11%; <2 cm 57%; 2-4 cm 28%; 4-6 cm 4%. The no rest and <2 cm (optimal operability) tumor was observed in T2: 94%; in T3: 73%; in the T4A: 0%. Severe side effects (Grade III-IV) were not observed. There was a significant decrease in size (P < 0.0001). Of the 100 surgical specimens, 83% had clear-, 9% close- and 8% involved margins. From T4A, there was a 40% (6 patients) involved margin. Based on the significantly better size and operability of primary T2-3, the mild side effects and the high (83%) percentage of clear surgical margins, that is better than other (without preoperative chemotherapy) results, sought the use of chemotherapy is recommended before surgery. Due to the 40% involved margin, we don't suggest surgery in T4A.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Female; Humans; Male; Methotrexate; Middle Aged; Mitolactol; Mouth Neoplasms; Neoadjuvant Therapy; Neoplasm Staging; Oral Surgical Procedures; Physicians; Surgery, Oral; Vincristine
PubMed: 19757193
DOI: 10.1007/s12253-009-9208-3 -
Progress in Neuro-psychopharmacology &... Jun 2009Depression and impaired quality of life (QOL) are frequently observed in patients suffering from a variety of diseases. In addition, it has been reported that an...
Depression and impaired quality of life (QOL) are frequently observed in patients suffering from a variety of diseases. In addition, it has been reported that an enhanced degradation of the serotonin precursor tryptophan may contribute to QOL deterioration in some diseases. However, it is unclear whether the correlation between the QOL scores and the central serotonergic tone is only mediated by the severity of either the depression symptoms or the physical illness itself. The present study examined the relationship between serotonin transporter (SERT) availability and life quality as measured by the World Health Organization Quality of Life brief version questionnaire (WHO-QOL) in healthy participants in order to exclude the influence of depressive mood and disease. The SERT availability in the midbrain was approximated using SPECT with [(123)I] ADAM ligand in fifty-eight healthy volunteers. The overall rating sub scores of the WHO-QOL correlated positively with serotonin transporter availability in the males. Central serotoninergic activity may play a role in the overall rating scores of the WHO-QOL.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Association; Brain; Doxorubicin; Female; Health Status; Humans; Iodine Isotopes; Male; Mitolactol; Mitomycins; Quality of Life; Serotonin Plasma Membrane Transport Proteins; Sex Factors; Surveys and Questionnaires; Tomography, Emission-Computed, Single-Photon; Young Adult
PubMed: 19332100
DOI: 10.1016/j.pnpbp.2009.03.018 -
European Journal of Cancer (Oxford,... Jun 2008In a previous randomised EORTC study on adjuvant dibromodulcitol (DBD) and bichloroethylnitrosourea (BCNU) in adults with glioblastoma multiforme (GBM) and anaplastic... (Randomized Controlled Trial)
Randomized Controlled Trial
Adjuvant dibromodulcitol and BCNU chemotherapy in anaplastic astrocytoma: results of a randomised European Organisation for Research and Treatment of Cancer phase III study (EORTC study 26882).
BACKGROUND
In a previous randomised EORTC study on adjuvant dibromodulcitol (DBD) and bichloroethylnitrosourea (BCNU) in adults with glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA), a clinically significant trend towards a longer overall survival (OS) and a progression-free survival (PFS) was observed in the subgroup of AA. The aim of the present study was to test this adjuvant regimen in a larger number of AA patients.
METHODS
Continuation of the previous phase III trial for newly diagnosed AA according to the local pathologist. Patients were randomised to either radiotherapy only or to radiotherapy in combination with BCNU on day 2 and weekly DBD, followed by adjuvant DBD and BCNU in cycles of six weeks for a maximum total treatment duration of one year. OS was the primary end-point.
RESULTS
Patients (193 ) with newly diagnosed AA according to local pathological assessment were randomised to radiotherapy (RT) alone (n=99), or to RT plus DBD/BCNU (n=94); 12 patients were considered not eligible. At central pathology review, over half (53%) of the locally diagnosed AA cases could not be confirmed. On intent-to-treat analysis, no statistically significant differences in OS (p=0.111) and PFS (p=0.087) were observed, median OS after RT was only 23.9 months 95% confidence interval (CI), [18.4-34.0] after RT plus DBD/BCNU 27.3 months 95% CI [21.4-46.8].
CONCLUSION
No statistically significant improvement in survival was observed after BCNU/DBD adjuvant chemotherapy in AA patients. The trend towards improved survival is consistent with previous reports. Central pathology review of grade 3 tumours remains crucial.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Carmustine; Chemotherapy, Adjuvant; Female; Hematologic Diseases; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mitolactol; Treatment Failure
PubMed: 18248979
DOI: 10.1016/j.ejca.2007.12.005 -
Zhonghua Zhong Liu Za Zhi [Chinese... Jun 2006To explore the expression of multidrug resistance gene 1 ( MDR1), glutathione-S-transferases-pi (GST-pi) in osteosarcoma and soft tissue sarcoma tissues from 34 patients...
OBJECTIVE
To explore the expression of multidrug resistance gene 1 ( MDR1), glutathione-S-transferases-pi (GST-pi) in osteosarcoma and soft tissue sarcoma tissues from 34 patients and their correlation with chemotherapy resistance.
METHODS
MDR1 and GST-pi expressions were analyzed by real-time fluorescence quantitative polymerase chain reaction (FQ-PCR) and flow cytometry (FCM) at mRNA and protein levels, respectively. Chemotherapy sensitivity on adriamycin, cisplatinum, fluorouracil, mitomycin C, dacarbazine, vincristine, methotrexate in tumor tissues were detected by MTT assay.
RESULTS
The nonsensitive rates on adriamycin, cisplatinum, fluorouracil, mitomycin C, dacarbazine, vincristine, methotrexate in tumor tissues were 41.18%, 17.7%, 47.1%, 50.0%, 76.5%, 61.8% and 52.9%, respectively. The expression of P-glycoprotein (P-gp) and GST-pi in tumor tissues was 1.54 and 2.58 (relative fluorescence intensity). Chi2 analysis showed that there was a positive correlation between P-gp expression and drug resistance on ADM, GST-pi expression and resistance on ADM, DDP and MMC (P < 0.05). There was not seen obvious correlation between expression of MDR1, GST-pi and age, gender, pathological type, tumor size in osteosarcoma and soft tissue sarcoma patients (P > 0.05). The expression of GST-pi was increased in patients receiving preoperative chemotherapy. The rate of postoperative recurrence was higher in patients with higher GST-pi expression level than those with lower GST-pi expression level before operation (P < 0.05).
CONCLUSION
Individual differences exist in chemotherapy sensitivity and expression of MDR1 and GST-pi in osteosarcoma and soft tissue sarcomas patients. Chemotherapy can induce up-regulation of GST-pi protein expression. Primary high expression of GST-pi is the main mechanism of resistance of osteosarcoma and soft tissue sarcomas to chemotherapy and is related to poor prognosis.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Child; Cisplatin; Doxorubicin; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Flow Cytometry; Follow-Up Studies; Glutathione S-Transferase pi; Humans; Male; Middle Aged; Mitolactol; Mitomycins; Osteosarcoma; Prognosis; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction; Sarcoma
PubMed: 17152492
DOI: No ID Found