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Cytometry 1992Pharmacologic effects of cisplatin (CDDP) and peplomycin (PEP) on tumor cell kinetics were studied both in vitro and in vivo with the aid of flow cytometry (FCM). Double...
Pharmacologic effects of cisplatin (CDDP) and peplomycin (PEP) on tumor cell kinetics were studied both in vitro and in vivo with the aid of flow cytometry (FCM). Double staining with propidium iodide (PI) and fluorescein isothiocyanate (FITC)-labeled bromodeoxyuridine (BrdU) was used to analyze the cell cycle, and the number of viable cells was determined with fluorescein diacetate (FDA). Effects of combining the 2 agents were also studied to establish the most effective method of combination therapy. Furthermore, these agents were tried clinically on the basis of experimental results. Results showed that CDDP exerted its action at the S and G2M phases in the cell cycle and PEP at the G2M phase. Among the combination regimens in the experiments with CDDP, PEP, and CDDP + PEP as analyzed by FCM, the strongest block on the G2M phase was shown in the one at a 2-day interval, resulting in the most effective killing of the tumor cells. Clinical trial of the combination therapy showed the same results as the in vitro experiment; the therapy proved useful for improving the patient's clinical condition and the results obtained with CT imaging and pathology.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bromodeoxyuridine; Carcinoma, Squamous Cell; Cell Cycle; Cisplatin; Flow Cytometry; G2 Phase; Humans; In Vitro Techniques; Male; Maxillary Neoplasms; Middle Aged; Peplomycin; S Phase; Tumor Cells, Cultured
PubMed: 1374308
DOI: 10.1002/cyto.990130313 -
Chembiochem : a European Journal of... Apr 2018Capillary electrophoresis, coupled with DNA 5' Texas Red labeling, was used to investigate the ability of MNase, Fe peplomycin, and duocarmycin B to access the...
Capillary electrophoresis, coupled with DNA 5' Texas Red labeling, was used to investigate the ability of MNase, Fe peplomycin, and duocarmycin B to access the nucleosome. Distinct accessibility patterns of these species to the nucleosome were observed. MNase was completely prevented from approaching the nucleosome core and exhibited a higher site specificity for targeting DNA sites located close to the core region. Intercalation of peplomycin in the nucleosomal core region was highly suppressed, but reaction sites located at the ends of the nucleosomal core remained accessible, which implied flexibility of the core DNA end. Duocarmycin B was able to enter and react in the core region, although its alkylating efficiency decreased significantly.
Topics: DNA; DNA Cleavage; Duocarmycins; Electrophoresis, Capillary; Ferrous Compounds; Indoles; Micrococcal Nuclease; Nucleosomes; Peplomycin; Pyrrolidinones
PubMed: 29334166
DOI: 10.1002/cbic.201700643 -
Hinyokika Kiyo. Acta Urologica Japonica Nov 1994We present a case report of a relapse to the mediastinal lymph node alone, 38 months after orchiectomy on surveillance for stage I typical seminoma. The patient, a... (Review)
Review
We present a case report of a relapse to the mediastinal lymph node alone, 38 months after orchiectomy on surveillance for stage I typical seminoma. The patient, a 63-year-old man, was treated with high inguinal orchiectomy for left testicular tumor and close follow-up. After 38 months from the initial treatment, the chest X-ray film and CT scan revealed mediastinal tumor. Fine needle aspiration cytology performed under the bronchoscopy showed seminoma cells. Complete remission was achieved after three courses chemotherapy of cisplatin, vincristine, methotrexate, peplomycin and etoposide (COMPE). He has continued to be clinically disease-free 8 months after completion of the treatment. According to the available data in the literature, 94% of the recurrences was detected within 3 years after orchiectomy, and 92% involved retroperitoneal lymph node metastases. This is a rare case who had a late relapse in the mediastinum alone.
Topics: Humans; Lymph Nodes; Lymphatic Metastasis; Male; Mediastinum; Middle Aged; Neoplasm Staging; Seminoma; Testicular Neoplasms
PubMed: 7832075
DOI: No ID Found -
BMC Cancer Dec 2020The prognosis of advanced oral cancer remains dismal. While multimodal therapy is beneficial, maintaining the quality of life of long-term survivors is important....
BACKGROUND
The prognosis of advanced oral cancer remains dismal. While multimodal therapy is beneficial, maintaining the quality of life of long-term survivors is important. Therefore, risk-adapted treatment regimens need to be designed. We herein investigated whether pathological responses in oral cancer patients treated with preoperative chemoradiotherapy predict locoregional recurrence.
METHODS
We retrospectively reviewed the data of 51 oral cancer patients who received preoperative radiotherapy and concurrent pepleomycin, followed by curative surgery at our institution between January 2009 and June 2018. Each patient received preoperative external beam irradiation to the primary tumor and lymphatics (2 Gy per day for approximately 3 weeks) concurrent with pepleomycin (2.5 mg/day). Surgery was performed approximately 3-4 weeks after the completion of preoperative chemoradiotherapy. Pathological responses were defined based on the grading system of Oboshi and Shimosato.
RESULTS
Eight, 22, 16, and 5 patients had Oboshi and Shimosato grades 2a, 2b, 3, and 4, respectively. Favorable pathological responses (grades 3 and 4) were observed in 41.2% of patients (21 out of 51 patients). The pathological response and number of pathological lymph node metastases were identified as significant prognostic factors for locoregional control in the univariate analysis. Three-year locoregional control rates were 100 and 56.6% in patients with favorable and unfavorable pathological responses, respectively.
CONCLUSIONS
The present study demonstrated that pathological tumor responses to preoperative chemoradiotherapy are a useful predictive factor for locoregional control.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Chemoradiotherapy; Female; Follow-Up Studies; Hematologic Diseases; Humans; Kaplan-Meier Estimate; Lymphatic Irradiation; Lymphatic Metastasis; Male; Middle Aged; Mouth Neoplasms; Neck Dissection; Neoadjuvant Therapy; Peplomycin; Pneumonia, Aspiration; Radiotherapy Dosage; Radiotherapy, Conformal; Retrospective Studies; Treatment Outcome; Xerostomia
PubMed: 33302897
DOI: 10.1186/s12885-020-07707-2 -
Hinyokika Kiyo. Acta Urologica Japonica Jan 1991Peplomycin emulsified in hydroxypropyl cellulosum (HPC-PEP) was prepared for intravesical chemotherapy. Clinical efficacy of HPC-PEP and tissue concentration of...
Peplomycin emulsified in hydroxypropyl cellulosum (HPC-PEP) was prepared for intravesical chemotherapy. Clinical efficacy of HPC-PEP and tissue concentration of peplomycin (PEP) were studied in 12 patients with bladder tumor. Histopathology showed transitional cell carcinoma; 2 in grade 1,8 in grade 2, and 2 in grade 3. The total volume of 30 ml HPC-PEP was prepared from a mixture of 2% HPC and 90 mg PEP in 15 ml saline, and was intravesically administered through a urethral catheter and retained for two hours. Clinical evaluation 7 days after the initial instillation demonstrated good tumor regression in 2, good response in 5, and no change in 5. The mean PEP level in tumor tissue was 0.36 microgram/gr after 7 days and 0.19 microgram/gr even after 14 days. These clinical observations and tissue levels of PEP suggest that HPC-PEP might be useful as an intravesical instillation agent for bladder tumor.
Topics: Administration, Intravesical; Adult; Aged; Bleomycin; Carcinoma, Transitional Cell; Cellulose; Delayed-Action Preparations; Emulsions; Female; Humans; Male; Middle Aged; Peplomycin; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 1707215
DOI: No ID Found -
European Journal of Surgical Oncology :... Mar 2015Patients with muscle-invasive bladder cancer (MIBC) often undergo various preoperative treatments to improve survival; however, their efficacy and safety remain unclear.
Efficacy and safety of systemic chemotherapy and intra-arterial chemotherapy with/without radiotherapy for bladder preservation or as neo-adjuvant therapy in patients with muscle-invasive bladder cancer: a single-centre study of 163 patients.
INTRODUCTION
Patients with muscle-invasive bladder cancer (MIBC) often undergo various preoperative treatments to improve survival; however, their efficacy and safety remain unclear.
MATERIALS AND METHODS
The anti-tumour effects and adverse events were evaluated in 163 MIBC patients who received systemic chemotherapy (SC, n = 34), intra-arterial chemotherapy (IAC, n = 50), or combined IAC and radiotherapy (IAC + R, n = 79).
RESULTS
Pathological complete responses were observed in 17.6%, 22.0%, and 43.0% of patients in the SC, IAC, and IAC + R groups, respectively, with respective 5-year overall survival rates of 42.0%, 46.7%, and 50.3%. Multivariate analysis showed that successful IAC + R protocol administration was a significant predictor for survival (hazard ratio = 0.16, p = 0.028). The incidence of severe adverse events was higher in the IAC + R group (36.7%) than in the SC (9.8%) and IAC groups (16.0%).
CONCLUSIONS
IAC + R was useful for patients with MIBC. Successful completion and optimal patient selection were important for this treatment strategy.
Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Transitional Cell; Chemoradiotherapy; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Cisplatin; Cystectomy; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Multivariate Analysis; Neoadjuvant Therapy; Neoplasm Invasiveness; Organ Sparing Treatments; Peplomycin; Prognosis; Treatment Outcome; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 25312685
DOI: 10.1016/j.ejso.2014.07.043 -
The Journal of Antibiotics Jul 1989The uptake of [3H]peplomycin-Cu(II) ([3H]PEP-Cu(II)) into various tumor cell lines was studied. The time course of [3H]PEP-Cu(II) uptake into AH66, AH66F, Ehrlich and...
The uptake of [3H]peplomycin-Cu(II) ([3H]PEP-Cu(II)) into various tumor cell lines was studied. The time course of [3H]PEP-Cu(II) uptake into AH66, AH66F, Ehrlich and P388 cells was biphasic. The first phase of uptake was completed within 5 minutes. The second, slower phase, of uptake into AH66, AH66F and Ehrlich cells increased linearly with incubation time, but that into P388 cells reached a plateau level. In L1210 cells, only the first rapid uptake was observed. The lower uptake into P388 and L1210 cells during the second phase may be related to their insensitivity to PEP. However, the uptake into AH66F cells was higher than that into AH66 cells, although AH66F cells were less sensitive to PEP than AH66 cells. Deamide PEP was detected in intact cells which had taken up [3H]PEP-Cu(II) during 4 hours. This confirmed that PEP-Cu(II) was transported into the cell, the copper removed and PEP metabolized to deamide PEP. [3H]PEP-Cu(II) uptake into AH66 and AH66F cells increased in proportion to the extracellular concentration of drug up to at least 200 micrograms/ml, suggesting that uptake was not mediated by a carrier system. Metabolic inhibitors such as NaN3 and 2,4-dinitrophenol enhanced [3H]PEP-Cu(II) uptake, but did not influence efflux. Uptake was also enhanced by membrane modifiers such as dibucaine and chlorpromazine which increase the fluidity of lipid membranes. The results suggest that PEP-Cu(II) was taken up into tumor cells by passive diffusion, controlled by an energy-dependent cell membrane barrier.
Topics: Animals; Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Ehrlich Tumor; Chlorpromazine; Chromatography, High Pressure Liquid; Colchicine; Dibucaine; Dose-Response Relationship, Drug; Leukemia L1210; Leukemia P388; Liver Neoplasms, Experimental; Peplomycin; Permeability; Time Factors; Tumor Cells, Cultured; Vinblastine
PubMed: 2473972
DOI: 10.7164/antibiotics.42.1163 -
Hinyokika Kiyo. Acta Urologica Japonica Nov 1994During the last 8 years, 70 cases of testicular tumor were treated in our department. Of them 2 cases had brain metastasis. Case 1; A 37-year-old male was admitted with... (Review)
Review
During the last 8 years, 70 cases of testicular tumor were treated in our department. Of them 2 cases had brain metastasis. Case 1; A 37-year-old male was admitted with the chief complaint of cough. Retroperitoneal lymph node and lung metastases were discovered (stage IIIB, pT4aN1M1). Resected right testis was diagnosed as embryonal carcinoma, teratoma and STGC histopathologically. After 3 courses of PVB (cisplatinum, vincristine, bleomycin) chemotherapy right hemiplegia occurred and computerized tomographic (CT) scan revealed brain metastasis. His general condition degraded rapidly and he died of brain herniation 3 months after orchiectomy. Case 2; A 32-year-old male was admitted because of right testicular swelling and lung metastases (stage IIIB, pTiN0M1). Pathological examination revealed embryonal carcinoma, yolk sac tumor and teratoma. After 4 courses of chemotherapy with cisplatinum (CDDP), vincristine, methotrexate, peplomycin, and etoposide all lung metastases were disappeared. A few months later left hemiplegia by brain metastasis appeared suddenly. Four additional courses of high dose chemotherapy and resection of brain metastasis was performed. Complete remission continued for 13 months. The prognosis of testicular tumor with brain metastasis was very poor. During the last 8 years, 21 cases of testicular tumor with brain metastasis were reported in the Japanese literature. A follow-up study of prognosis in the literature was performed and discussed.
Topics: Adult; Brain Neoplasms; Carcinoma, Embryonal; Endodermal Sinus Tumor; Humans; Lung Neoplasms; Male; Prognosis; Teratoma; Testicular Neoplasms
PubMed: 7832076
DOI: No ID Found -
Japanese Journal of Cancer Research :... May 1999We investigated the relationship between manganese superoxide dismutase (Mn-SOD) activity and apoptosis induced by anticancer drugs and radiation. Although the activity...
We investigated the relationship between manganese superoxide dismutase (Mn-SOD) activity and apoptosis induced by anticancer drugs and radiation. Although the activity of copper, zinc-SOD did not differ greatly among 9 squamous cell carcinoma (SCC) cell lines (OSC-1 to OSC-9), the Mn-SOD activity did differ among the cell lines. The Mn-SOD activity was increased by treatments with 5-fluorouracil (5-FU), peplomycin and 137Cs, reaching plateau levels at 12 h after treatment and then decreasing gradually. When OSC-1 and OSC-3, and OSC-2 and OSC-4 were examined as representative cell lines with low and high Mn-SOD activity, respectively, the decrease was more prominent in OSC-1 and OSC-3 than in OSC-2 and OSC-4. The intracellular levels of superoxide and hydrogen peroxide (H2O2) were increased after treatment with the anticancer agents, and the increases were larger in OSC-1 and OSC-3 than in OSC-2 and OSC-4. The decrease of mitochondrial membrane potential (deltapsi(m)) by the anticancer agents was marked in OSC-1 and OSC-3. Correspondingly, the release of cytochrome c, the activation of caspase-3 and the cleavage of poly(ADP-ribose)polymerase were stronger in OSC-3 than in OSC-4. In addition, apoptosis induced by the anticancer agents was prominent in OSC-3, exhibiting a close relationship with the deltapsi(m) and the H2O2 level. These results indicate that Mn-SOD in SCC cells modulates apoptosis induction and the inactivation of Mn-SOD might be a promising strategy for SCC treatment.
Topics: Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Squamous Cell; Cell Survival; Fluorouracil; Gamma Rays; Humans; Hydrogen Peroxide; Mice; Peplomycin; Superoxide Dismutase
PubMed: 10391096
DOI: 10.1111/j.1349-7006.1999.tb00783.x -
International Journal of Experimental... Aug 2001To analyse the mechanism by which a bleomycin derivative, peplomycin (PLM) induces pulmonary fibrosis, we investigated differentiation of rat pulmonary fibroblasts to...
To analyse the mechanism by which a bleomycin derivative, peplomycin (PLM) induces pulmonary fibrosis, we investigated differentiation of rat pulmonary fibroblasts to myofibroblasts (MF). In intraperitoneally PLM (5 mg/kg/day)-injected rats, the peripheries of lungs adjacent to the pleura revealed advanced fibrosis with a small number of alpha-smooth muscle actin (alpha-SMA)-positive MF, which ultrastructurally possessed abundant microfilaments and cellular organelles. In the fibrotic tissue, the expression of alpha-SMA-mRNA was detected by in situ reverse transcription-polymerase (RT-PCR). The message was strong just after a 2-week administration of PLM then decreased thereafter, although fibrosis advanced. When pulmonary fibroblasts were separated from saline-injected rats (N-Fib) and cultivated for 7 days in the presence of 5 mg/mL PLM, alpha-SMA protein was weakly expressed, while the majority of pulmonary fibroblasts separated from PLM-injected rats (P-Fib) became positive for alpha-SMA in 7-day cultivation and the expression of alpha-SMA in P-Fib was strongly increased by cultivation in the presence of PLM and transforming growth factor-beta (TGF-beta), but not basic fibroblast growth factor (bFGF) or platelet-derived growth factor (PDGF), although the cell proliferation was most strongly enhanced by bFGF and only slightly by PLM and TGF-beta. The alpha-SMA-positive cells expressed vimentin, but only weakly expressed desmin. Additionally, P-Fib generated larger amounts of TGF-beta and bFGF than were generated by N-Fib. These results indicate that PLM induces pulmonary fibrosis by differentiating fibroblasts to alpha-SMA-positive MF, and that bFGF and TGF-beta play each critical role in the different phases of PLM-induced pulmonary fibrosis by inducing fibroblast proliferation and transformation, respectively.
Topics: Actins; Animals; Antibiotics, Antineoplastic; Blotting, Northern; Blotting, Western; Cell Culture Techniques; Cell Differentiation; Cell Division; Fibroblast Growth Factor 2; Fibroblasts; Gene Expression Regulation; Male; Peplomycin; Pulmonary Fibrosis; RNA, Messenger; Rats; Rats, Inbred F344; Reverse Transcriptase Polymerase Chain Reaction; Transforming Growth Factor beta
PubMed: 11493347
DOI: 10.1111/j.1365-2613.2001.iep0082-0231-x