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Yakugaku Zasshi : Journal of the... 2011No true immunocytochemistry (ICC) for drugs nor its application to pharmacokinetic studies is available. Recently, our studies have shown that ICC for drugs is extremely... (Review)
Review
No true immunocytochemistry (ICC) for drugs nor its application to pharmacokinetic studies is available. Recently, our studies have shown that ICC for drugs is extremely useful for such studies by utilizing easy and safe techniques, and gives direct evidence of drug localization. We have therefore developed antibodies and a series of pretreatment conditions for the immunodetection of drugs and have localized sites of drug uptake or accumulation in several tissues of rats following the administration of drugs. This review describes preparation of anti-drug antibody, specificity of antibody, fixation of drug in situ in rat tissues and cells, treatment of paraffin section specimens prior to immunoreaction, precision, and their application to a variety of types of antibiotics anti-cancer anthracyclines daunorubicin, doxorubicin, and epirubicin, bleomycin analog peplomycin, antimicrobial agents gentamicin, and amoxicillin. ICC for the anti-cancer anthracyclines demonstrated that the drug accumulates in a characteristic pattern in the heart, liver, kidney, gastrointestinal tract, and hair follicles, which represent the sites targeted by the drug toxicity. Some, but not all, of these drug accumulations are associated with the induction of apoptosis. It was also noted that there are striking differences in accumulation among the anthracyclines in rat tissues, maybe contributing the mechanisms of the differences in anti-tumor activities of the anthracyclines. Both ICCs for gentamicin and peplomycin identified characteristic necrotic-like cells in the specific sites of the kidney, suggesting the sites are readily affected by some chemotherapeutic agents. ICC for amoxicillin demonstrated that the sites of the drug accumulation in small intestine, liver and kidney are closely correlated with the specific sites in which certain transporter systems for penicillin occur. Thus, an ICC method is a potential new tool for pharmacokinetic studies of wide variety types of drugs containing a primary amino group(s) in their molecules.
Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Cells; Gentamicins; Hair Follicle; Immunohistochemistry; Kidney; Liver; Rats; Sensitivity and Specificity; Tissue Distribution
PubMed: 21628984
DOI: 10.1248/yakushi.131.949 -
Nihon Hinyokika Gakkai Zasshi. the... Jan 1992It had been believed that carcinoma of the penis was rather rare in the developed countries comparing with that in the under-developing countries, however, the recent... (Review)
Review
It had been believed that carcinoma of the penis was rather rare in the developed countries comparing with that in the under-developing countries, however, the recent epidemiological studies failed to reveal any clear difference of the incidence of carcinoma of the penis all over the world. In these days so called successful treatment is coming to be evaluated by the quality of life (QOL) after surgical or nonsurgical treatment (especially sexual function tended to be considered very important factors altering QOL). I want to emphasize the following issues in this report. 1. Erythroplasia of Queyrat and Bowen's disease are carcinoma in situ and should be dealt as carcinoma of the penis. 2. relation of human papilloma virus and carcinoma of penis. 3. usefulness of TNM classification over Jackson's classification. 4. SCC antigen is a reliable tumor marker of carcinoma of the penis? 5. effectiveness of chemotherapy based on BLM combined with radiation therapy for carcinoma of the penis. 6. usefulness of Mohs microscopically controlled surgery and modified groin dissection. It is generally accepted that since carcinoma of the penis is a rare disease and for one institution up to 50 cases can be experienced during 20 years in Japan, there exist no integrated study involving a large number of institutions. I really wish a certain form of group study to be completed and the results from this study utilized to overcome the present problems for the treatment of carcinoma of the penis.
Topics: Antibiotics, Antineoplastic; Bleomycin; Combined Modality Therapy; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Neoplasm Staging; Penile Neoplasms; Penile Prosthesis; Peplomycin; Prognosis; Quality of Life; Radiotherapy
PubMed: 1373451
DOI: 10.5980/jpnjurol1989.83.1 -
The Journal of Antibiotics Apr 1986The unstability of neocarzinostatin (NCS), apo-NCS and NCS-chromophore (NCS-chr) has been investigated by using an extra-weak chemiluminescence (CL) analyzer. A...
The unstability of neocarzinostatin (NCS), apo-NCS and NCS-chromophore (NCS-chr) has been investigated by using an extra-weak chemiluminescence (CL) analyzer. A significantly high emission intensity (10,840 counts/10 seconds) was detected from NCS under dark conditions at 20 degrees C, while no significant emission was observed in other antitumor antibiotics, such as, mitomycin C and pepleomycin. This high emission intensity of NCS was due to NCS-chr I (epoxide form) but not apo-NCS. The functional group generating the high extra-weak CL of NCS-chr I is probably the epoxide in the molecule, since the emission intensity of NCS-chr I (epoxide form) is much higher than that of NCS-chr II (hydrochloride adduct form). The extra-weak CL emission of NCS decreased under a nitrogen atmosphere and it was greatly enhanced under an oxygen atmosphere. The spectral analysis of NCS showed emission peaks around 460 and 570 nm. These observations strongly suggest that one of the emission species of NCS-chr may be due to singlet oxygen.
Topics: Antibiotics, Antineoplastic; Bleomycin; Drug Stability; Enediynes; Luminescent Measurements; Mitomycin; Mitomycins; Peplomycin; Powders; Spectrophotometry; Structure-Activity Relationship; Zinostatin
PubMed: 2423490
DOI: 10.7164/antibiotics.39.535 -
The Journal of Antibiotics Sep 1985Rabbit antisera highly specific to the bleomycinic acid moiety of bleomycins were obtained by immunizing with a conjugate of copper-complex of bleomycin A5 and bovine...
Rabbit antisera highly specific to the bleomycinic acid moiety of bleomycins were obtained by immunizing with a conjugate of copper-complex of bleomycin A5 and bovine serum albumin. These antisera not only reacted with bleomycin A5 but also with other bleomycins such as bleomycin A2, bleomycin B2 and peplomycin. The antisera showed little cross-reactivity with deamido-, depyruvamido- and decarbamoyl-bleomycins. Thus, these antisera were found to be highly specific for the intact bleomycinic acid moiety. One of the antisera was successfully applied to radioimmunoassay of bleomycin and peplomycin in mouse and human sera. The detection limit was 1 ng/ml. This radioimmunoassay is expected to be widely used for the determination of active bleomycins in biological and clinical samples.
Topics: Animals; Bleomycin; Cross Reactions; Humans; Peplomycin; Rabbits; Radioimmunoassay
PubMed: 2415502
DOI: 10.7164/antibiotics.38.1251 -
Anticancer Research 2008The antitumor antibiotic peplomycin showed higher cytostatic antiproliferative effect on five cultured human oral squamous cell carcinoma (OSCC) cell lines (HSC-2,...
The antitumor antibiotic peplomycin showed higher cytostatic antiproliferative effect on five cultured human oral squamous cell carcinoma (OSCC) cell lines (HSC-2, HSC-3, HSC-4, Ca9-22 and NA), as compared with three human oral normal cells (gingival fibroblast HGF, pulp cell HPC and periodontal ligament fibroblast HPLF). Although the antiproliferative activity of peplomycin declined with increasing cell density, peplomycin showed tumor-specific cytotoxicity at any cell density. The five OSCC cell lines showed considerable differences in sensitivity against peplomycin; the HSC-2 cells were the most sensitive, followed by the NA, HSC-3, Ca9-22 and HSC-4 cells. Peplomycin did not induce internucleosomal DNA fragmentation in any of the five OSCC cell lines, and only slightly modified caspase-3, -8 and -9 activities in the HSC-2, Ca9-22 and NA cell lines. Electron microscopy revealed that peplomycin induced the vacuolation of mitochondria accompanying electron lucent matrices lacking cristae and the enlargement of the endoplasmic reticulum in the HSC-2 cells. These data suggest that the anti-proliferative effect of peplomycin is time-dependent, and therefore prolonged treatment with peplomycin in combination with cytotoxic chemotherapeutic agents may induce greater cytotoxic action.
Topics: Antibiotics, Antineoplastic; Carcinoma, Squamous Cell; Cell Death; Cell Line, Tumor; Fibroblasts; Humans; Microscopy, Electron; Mouth Neoplasms; Peplomycin
PubMed: 18751395
DOI: No ID Found -
The Journal of Antibiotics Aug 1983Effect of peplomycin sulfate (PLM) on pulmonary fibrosis was examined. Hydroxyproline, uronic acid, proline hydroxylase (EC 1.14.11.2) and glucosamine 6-phosphate... (Comparative Study)
Comparative Study
Peplomycin sulfate and pulmonary fibrosis: hydroxyproline, uronic acid, proline hydroxylase and glucosamine 6-phosphate synthetase in lungs of hamsters treated with peplomycin.
Effect of peplomycin sulfate (PLM) on pulmonary fibrosis was examined. Hydroxyproline, uronic acid, proline hydroxylase (EC 1.14.11.2) and glucosamine 6-phosphate synthetase (EC 2.6.1.16) in lungs of hamsters treated with PLM were studied and compared with those of hamsters treated with bleomycin (BLM). PLM, when administered intraperitoneally, one injection daily for 10 consecutive days, at either a high- (5 mg/kg) or low- (2.8 mg/kg) dosage-level, caused no significant increase of lung hydroxyproline and uronic acid as compared with controls. BLM on the other hand effected a significant increase in lung hydroxyproline on the high-dosage level (5 mg/kg) but not on the low-dosage level (2.8 mg/kg). In contrast, when administering PLM intratracheally, the concentrations of hydroxyproline in lungs increased 20% over the control levels. A transient increase of proline hydroxylase and glucosamine 6-phosphate synthetase also occurred shortly after the instillation. These increases were also observed in the corresponding groups treated with BLM, which confirmed the previous observations by other investigators. However, the magnitude of the increase was relatively lower in those values of PLM as compared with those of BLM. These data suggested that (1) PLM, when administered with multiple dosages intraperitoneally, showed no significant effect on the elevation of lung hydroxyproline; (2) PLM, when administered with a dose intratracheally, induced pulmonary fibrosis similar to that caused by BLM. However, the hydroxyproline accumulation in lungs of PLM-treated hamsters was less than in those of the BLM-treated; (3) The fibrotic effect on the lungs caused by either PLM or BLM was probably attributed to acceleration of the syntheses of collagen and acidic glycosaminoglycans.
Topics: Animals; Anti-Bacterial Agents; Bleomycin; Carbohydrate Epimerases; Cricetinae; Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing); Hydroxyproline; Kinetics; Lung; Mesocricetus; Peplomycin; Procollagen-Proline Dioxygenase; Pulmonary Fibrosis; Structure-Activity Relationship; Time Factors; Uronic Acids
PubMed: 6195141
DOI: 10.7164/antibiotics.36.1067 -
Anticancer Research 2006Three antitumor antibiotics, mitomycin C, bleomycin sulfate and peplomycin sulfate, were compared for their tumor-specific cytotoxicity, using human oral squamous cell... (Comparative Study)
Comparative Study
Three antitumor antibiotics, mitomycin C, bleomycin sulfate and peplomycin sulfate, were compared for their tumor-specific cytotoxicity, using human oral squamous cell lines (HSC-2, HSC-3, HSC-4, Ca9-22 and NA), human promyelocytic leukemic cell line HL-60 and human normal oral cell types (gingival fibroblast HGF, pulp cell HPC and periodontal ligament fibroblast HPLF). Among these three compounds, mitomycin C showed the highest tumor-specificity, due to its higher cytotoxic activity against human oral tumor cell lines than bleomycin and peplomycin. However, there was considerable variation of drug sensitivity among the six tumor cell lines. Mitomycin C induced internucleosomal DNA fragmentation and caspase-3, -8 and -9 activation in HL-60 cells only after 24 h. On the other hand, mitomycin C induced no clear-cut DNA fragmentation in HCS-2 cells, although it activated caspase-3, -8 and -9 to a slightly higher extent. Western blot analysis demonstrated that mitomycin C did not induce any apparent change in the intracellular concentration of anti-apoptotic protein (Bcl-2) and pro-apoptotic proteins (Bax, Bad). Electron microscopy of mitomycin C-treated HL-60 cells showed intact mitochondria (as regards to integrity and size) and cell surface microvilli, without production of an apoptotic body or autophagosome, at an early stage after treatment. The present study suggests the incomplete induction of apoptosis or the induction of another type of cell death by mitomycin C treatment.
Topics: Antibiotics, Antineoplastic; Apoptosis; Bleomycin; Carcinoma, Squamous Cell; Caspases; Cell Death; Cells, Cultured; Enzyme Activation; Fibroblasts; HL-60 Cells; Humans; Mitomycin; Mouth Neoplasms; Peplomycin; Ultraviolet Rays
PubMed: 17094455
DOI: No ID Found -
Japanese Journal of Medicine 1989The present communication describes a patient with paraganglioma found in the retroperitoneum and neck. She was treated with the combination chemotherapy employing... (Review)
Review
The present communication describes a patient with paraganglioma found in the retroperitoneum and neck. She was treated with the combination chemotherapy employing cyclophosphamide, doxorubicin, and cisplatin (CAP therapy), and resulted in remarkable regression of the tumor in size. We reviewed the literature about the therapy of paraganglioma and the nature of retroperitoneal paraganglioma in relation with this case.
Topics: Aclarubicin; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Female; Head and Neck Neoplasms; Humans; Paraganglioma; Peplomycin; Retroperitoneal Neoplasms; Tomography, X-Ray Computed; Ultrasonography
PubMed: 2483851
DOI: 10.2169/internalmedicine1962.28.772 -
Hinyokika Kiyo. Acta Urologica Japonica Aug 1991CDDP combined chemotherapy was performed in 55 cases out of 229 prostatic cancer patients who were treated in Nara Medical University and Nara Prefectural Nara Hospital...
CDDP combined chemotherapy was performed in 55 cases out of 229 prostatic cancer patients who were treated in Nara Medical University and Nara Prefectural Nara Hospital between January 1979 and August 1989. The previously untreated 33 patients received chemotherapy with anti-androgen treatment as an initial treatment, as well as 7 cases of unresponsive to antiandrogen treatment, 14 relapsing cases and one case with recurrence after total prostatectomy. The major regimens of chemotherapy were cis-diammine dichloroplatinum (CDDP) alone in 16 cases, PVB regimen (bleomycin or peplomycin + vincristine + CDDP) in 19 cases, and CAP regimen (cyclophosphamide + adriamycin + CDDP) in 16 cases. Complete response was not achieved or partial response was observed in 20 cases (34%), no change was seen in 20 cases (34%), and progression was seen in 19 cases (32%). Among each evaluable lesion, effects (CR + PR) were observed in 40% in the prostate, in 18% in the bone lesions, in 44% in the soft tissue lesions, and in 42% in the prostatic tumor marker. The 7-year survival rate of the chemotherapy group (35.6%) was better than that of the antiandrogen treatment group (26.6%) in stage D patients, but was not significant statistically When evaluated by the regimen, a partial response was observed in 56% of CDDP alone, in 21% of PVB regimen, and in 38% of the CAP regimen. However, there was no significant difference in survival rate among the regimens. As an adverse effect, myelosuppression and renal toxicity seemed to be dose limiting factors of CDDP combined chemotherapy for advanced prostatic cancer patients.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bleomycin; Cisplatin; Combined Modality Therapy; Doxorubicin; Drug Evaluation; Humans; Male; Middle Aged; Neoplasm Staging; Phosphoramide Mustards; Prostatic Neoplasms; Survival Rate; Vinblastine
PubMed: 1720273
DOI: No ID Found -
Biochemical Pharmacology Jan 1989Bleomycin (BLM) hydrolase is believed to protect both malignant and normal tissue from the toxicity of the antitumor drug BLM. Little is known about the substrate...
Bleomycin (BLM) hydrolase is believed to protect both malignant and normal tissue from the toxicity of the antitumor drug BLM. Little is known about the substrate specificity of BLM hydrolase. Thus, we developed ion-paired reverse phase high speed liquid chromatography systems to assay for the metabolism of several BLM analogs. We found that BLM A2, BLM B2, tallysomycin S10b (TLM S10b), peplomycin (PEP), butylamino-3-propylamino-3-propylamine bleomycin (BAPP), deglyco bleomycin A2 (dgBLM A2) and bleomycinic acid were each metabolized by rabbit lung BLM hydrolase to a single metabolite. When compared to their corresponding parent compounds, these metabolites were 6- to 35-fold less potent in their ability to inhibit the proliferation of A-253 human head and neck squamous carcinoma cells in culture. Furthermore, we found that substitutions in various regions of the BLM molecule greatly affected the kinetic parameters of BLM hydrolase. For example, the Km with BLM B2 (0.056 +/- 0.005 mM) was 15-fold lower than that seen with BLM A2 (0.83 +/- 0.11 mM). In contrast, the Vmax was not affected markedly by these terminal amine substitutions but was influenced greatly by deletion of the carbohydrate groups of BLM. For example, a 4-fold higher Vmax was observed with dgBLM A2 compared to BLM A2. Thus, these results demonstrate that BLM hydrolase can recognize and metabolize a broad spectrum of BLM analogs regardless of their structural features. This enzymatic conversion resulted in the inactivation of the BLMs as demonstrated by a substantial decrease in their cytotoxicity. Furthermore, the terminal amine and carbohydrate regions, respectively, dictate the apparent affinity and the rate of metabolism of BLM hydrolase substrates.
Topics: Animals; Bleomycin; Cell Division; Cysteine Endopeptidases; Glycoside Hydrolases; Humans; Kinetics; Rabbits; Substrate Specificity; Tumor Cells, Cultured
PubMed: 2462878
DOI: 10.1016/0006-2952(89)90160-3