-
Journal of Oral Pathology & Medicine :... Jul 2003The therapies for refractory ulcers on the oral mucosa are symptomatic and very unsatisfactory. We hypothesized that application of growth factors might be able to...
BACKGROUND
The therapies for refractory ulcers on the oral mucosa are symptomatic and very unsatisfactory. We hypothesized that application of growth factors might be able to achieve successful remission of the lesion. We evaluated the effects of systemic administration and topical application of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) on impaired wound healing of ulcers in the rabbit gingiva.
METHODS
Almost uniform round ulcers could be created on the gingiva of the rabbits by chemical injury with acetic acid. When the submandibular glands were removed or i.v. injection of cisplatin (CDDP) and peplomycin sulfate was performed before ulcer formation, healing of the ulcers took longer than in untreated rabbits. To ascertain whether or not human EGF and bFGF affect rabbit cells, we first examined the effects of EGF and bFGF on the proliferation of the cells derived from rabbit gingiva. We then applied EGF or bFGF in these impaired healing models.
RESULTS
EGF and bFGF promoted proliferation of the fibroblasts, and EGF also promoted proliferation of the keratinocytes isolated from gingival tissue of rabbits in vitro. Systemic injections of EGF and bFGF in rabbits, which had their submandibular glands removed, and topical application of bFGF accelerated healing of ulcers created in rabbits injected with CDDP and peplomycin sulfate. The ability of bFGF to promote the healing of ulcers was much greater than that of EGF.
CONCLUSION
Basic FGF may be effective for refractory oral mucosal lesions.
Topics: Administration, Topical; Animals; Cell Division; Cisplatin; DNA; Disease Models, Animal; Epidermal Growth Factor; Female; Fibroblast Growth Factor 2; Gingiva; Humans; Injections, Intravenous; Mouth Mucosa; Oral Ulcer; Peplomycin; Rabbits; Submandibular Gland; Wound Healing
PubMed: 12787043
DOI: 10.1034/j.1600-0714.2003.t01-1-00111.x -
Biochemistry Jun 2003The identity of the axial ligand contributed by the drug in hydroperoxide-Co(III)-bleomycin and hydroperoxide-Co(III)-deglycobleomycin has been in doubt. With each...
Identification of the internal axial ligand of HO2-cobalt(III)-bleomycin: 1H[15N] HSQC NMR investigation of bleomycin, deglycobleomycin, and their hydroperoxide-cobalt(III) complexes.
The identity of the axial ligand contributed by the drug in hydroperoxide-Co(III)-bleomycin and hydroperoxide-Co(III)-deglycobleomycin has been in doubt. With each structure, a combination of (1)H[(15)N] HSQC and HMBC and (1)H COSY and NOESY NMR spectroscopy was used to observe and completely assign the nonaromatic (15)N chemical shifts of natural abundance bleomycin in the two hydroperoxide-Co(III) structures. Together with the (15)N assignments from a published 1D (15)N spectrum, the results permitted the assignment of the primary amine nitrogen to an axial ligand position in both structures.
Topics: Bleomycin; Cobalt; Ligands; Magnetic Resonance Spectroscopy; Models, Chemical; Nitrogen; Peplomycin; Protein Binding; Protons; Temperature
PubMed: 12767239
DOI: 10.1021/bi030016c -
Gan To Kagaku Ryoho. Cancer &... Mar 2003The aim of the present study was to examine the usefulness of neoadjuvant intraarterial chemotherapy (NAC) using nedaplatin as key drug to improve the prognosis in case... (Review)
Review
The aim of the present study was to examine the usefulness of neoadjuvant intraarterial chemotherapy (NAC) using nedaplatin as key drug to improve the prognosis in case of advanced cervical cancer. Twenty-five cases of advanced cervical cancer (15 cases of stage II with high risks, 10 of stage III, referred to as the 254-S group) treated by NAC using nedaplatin, mitomycin C and peplomycin were compared with 30 cases (22 cases of stage II with high risks, 8 of stage III, referred to as the CDDP group) treated using cisplatin and mitomycin C which is the conventional regimen, in terms of measurable response, pathological response, rate of lymph node metastasis, cumulative survival rate, side effects and relapse style. According to the evaluation by measurable responses, the response rate was 90% (CR 52%) in the 254-S group and 75% (CR 15%) in the CDDP group. For pathological response of the specimen, the CR rate was 16% in the 254-S group and 23% in the CDDP group. The rate of lymph node metastasis extracted surgically was 33% and 41%, respectively. The cumulative survival rate in the 254-S group was about 10% better than in the CDDP group, but no significant difference was found. Leucopenia of both groups was of the same grade. In the 254-S group, although thrombocytopenia was more critical than in the CDDP group, there was a slight tendency to kidney toxicity. The locoregional recurrence rate was 12% in the 254-S group and 30% in the CDDP group. The distant metastasis rate was 16% and 27%, respectively. Although neoadjuvant intraarterial chemotherapy using nedaplatin as a key drug was useful to improve the prognosis of advanced cervical cancer, measures against recurrence outside the pelvis and individualization of medical treatment were considered to lead to a further improvement of the prognosis.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Female; Humans; Infusions, Intra-Arterial; Lymphatic Metastasis; Middle Aged; Mitomycin; Neoadjuvant Therapy; Organoplatinum Compounds; Peplomycin; Prognosis; Survival Rate; Uterine Cervical Neoplasms
PubMed: 12669397
DOI: No ID Found -
Gynecologic and Obstetric Investigation 2002The evolution of therapy for malignant ovarian germ cell tumors is one of the true success stories in oncology. Treatment outcome has improved greatly thanks to...
The evolution of therapy for malignant ovarian germ cell tumors is one of the true success stories in oncology. Treatment outcome has improved greatly thanks to cisplatin-based combination chemotherapy. According to the well-established treatment guidelines for advanced cases, we treated a case of stage IV undifferentiated germ cell tumor in which we were able to preserve the patient's fertility. We concluded that the PEP regimen is an effective treatment for the patient with metastatic germ cell tumor.
Topics: Adult; Airway Obstruction; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Diagnosis, Differential; Dysgerminoma; Etoposide; Female; Head and Neck Neoplasms; Humans; Neoplasm Staging; Peplomycin; Radionuclide Imaging; Tomography, X-Ray Computed
PubMed: 12566754
DOI: 10.1159/000067716 -
Journal of Biological Inorganic... Jan 2003Binding structures of metal complexes of deglyco-peplomycin (dPEP) on DNA were investigated by comparing dPEP complexes with those of bleomycin (BLM) using DNA fiber EPR...
Binding structures of metal complexes of deglyco-peplomycin (dPEP) on DNA were investigated by comparing dPEP complexes with those of bleomycin (BLM) using DNA fiber EPR spectroscopy. A low spin species of Fe(III)dPEP observed in the DNA pellet changed irreversibly to several high spin species after the fabrication of the DNA fibers. The g values of the high spin species were different from those of Fe(III)BLM. The high spin species could not be nitrosylated reductively to ON-Fe(II)dPEP, suggesting that some nitrogen atoms coordinated to the Fe(III) were displaced on the DNA fibers. On the other hand, O(2)-Co(II)dPEP remained intact on the fibers similarly to O(2)-Co(II)BLM but with an increased randomness in the orientation on the DNA. In contrast to Cu(II)BLM, a considerable amount of Cu(II)dPEP bound almost randomly on B-form DNA fibers. These results indicated that the sugar moiety in peplomycin or bleomycin is playing an important role in enhancing the stability of the metal-binding domain and in the stereospecificity of the binding on DNA.
Topics: Animals; Antibiotics, Antineoplastic; Bleomycin; Copper; DNA; DNA Adducts; Electron Spin Resonance Spectroscopy; Ferrous Compounds; Glucose; Glycosylation; Male; Mannose; Molecular Structure; Nitrogen; Organometallic Compounds; Peplomycin; Salmon; Spermatozoa; Stereoisomerism
PubMed: 12459908
DOI: 10.1007/s00775-002-0398-3 -
APMIS : Acta Pathologica,... Jun 2002The co-existence of an endometrioid adenocarcinoma with an ovarian yolk sac tumor is very rare. Only eight cases have been reported in the English language literature. A... (Comparative Study)
Comparative Study
The co-existence of an endometrioid adenocarcinoma with an ovarian yolk sac tumor is very rare. Only eight cases have been reported in the English language literature. A 54-year-old postmenopausal woman with a 6-month history of progressive abdominal distension was seen at our hospital. MR imaging revealed a large cyst with a solid intramural node. Serum alpha-fetoprotein and CA125 levels were 13143 ng/ml and 170 U/ml, respectively. At laparotomy, a large tumor approximately 20 cm in diameter was found to occupy the abdominal cavity, adhering to the swollen appendix and part of the omentum. Microscopically, foci of endometrioid adenocarcinoma together with a yolk sac tumor component were observed within a large endometriotic cyst. Since the tumor was clinically staged 1c, the patient was given 500 mg of intraperitoneal carboplatin postoperatively, followed by five courses of combination chemotherapy consisting of cisplatin, etoposide and peplomycin at 4-week intervals. The levels of both serum alpha-fetoprotein and CA 125 decreased gradually to normal ranges and remained normal at the most recent follow-up on 29 December, 2001. In contrast to a very poor prognosis of this tumor in previously reported cases, our patient showed no sign of recurrence during a 21-month follow-up period.
Topics: Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Carcinoma, Endometrioid; Endodermal Sinus Tumor; Female; Humans; Immunohistochemistry; Middle Aged; Neoplasms, Multiple Primary; Ovarian Neoplasms; Postmenopause; alpha-Fetoproteins
PubMed: 12193212
DOI: 10.1034/j.1600-0463.2002.100609.x -
Hinyokika Kiyo. Acta Urologica Japonica Jan 2002We report a case of regionally metastatic pure squamous cell carcinoma of the urinary bladder successfully treated with combined radiation and chemotherapy in a...
We report a case of regionally metastatic pure squamous cell carcinoma of the urinary bladder successfully treated with combined radiation and chemotherapy in a 46-year-old man. Clinical staging was T3bN2M0. The patient received 50 Gy external radiation combined with intraarterial and systemic chemotherapy. Pathological complete response was found both in bladder and regional lymph nodes when he underwent radical cystectomy and lymph node dissection. The patient has been alive without evidence of disease for two years postoperatively.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Doxorubicin; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Peplomycin; Radiotherapy Dosage; Urinary Bladder Neoplasms
PubMed: 11868383
DOI: No ID Found -
Journal of Biological Inorganic... Jan 2002X-ray absorption spectroscopy (XAS) is used to study ferrous complexes of a bleomycin (BLM) congener, peplomycin (PEP), and two of its derivatives, iso-peplomycin (ISO)...
X-ray absorption spectroscopy (XAS) is used to study ferrous complexes of a bleomycin (BLM) congener, peplomycin (PEP), and two of its derivatives, iso-peplomycin (ISO) and depyruvamide peplomycin (DP), in which potential axial ligands have been perturbed and removed, respectively. Application of extended X-ray absorption fine structure analysis shows an elongation of the short-distance component of the first coordination sphere in DP and ISO relative to PEP. The XAS pre-edge intensity concomitantly decreases with increased axial perturbation. The short-distance component of PEP is correlated to the Fe-pyrimidine bond and is related to the amount of pi-back-bonding. Thus, the XAS analysis of these complexes provides structural information relevant to their differences in O2 reactivity.
Topics: Anti-Bacterial Agents; Bleomycin; Ferrous Compounds; Iron; Oxygen; Peplomycin; Pyrimidines; Spectrum Analysis; X-Rays
PubMed: 11862552
DOI: 10.1007/s007750100283 -
International Journal of Cancer Nov 2001ROIs and their scavengers are associated with apoptosis induction by anticancer drugs and gamma-rays, but the details have not been clarified. We examined the effect of...
Mn-SOD antisense upregulates in vivo apoptosis of squamous cell carcinoma cells by anticancer drugs and gamma-rays regulating expression of the BCL-2 family proteins, COX-2 and p21.
ROIs and their scavengers are associated with apoptosis induction by anticancer drugs and gamma-rays, but the details have not been clarified. We examined the effect of transfection of Mn-SOD antisense on apoptosis by 5-FU, PLM, CDDP and gamma-rays using nu/nu mice. After inoculation of Mn-SOD antisense-transfected SCC cells into the subcutis of each mouse's back, they slowly multiplied to form tumors sized 1,460 +/- 70 mm(3) at day 60, while control vector-transfected SCC cells rapidly multiplied, with a mean tumor size of 2,330 +/- 220 mm(3). Inversely, mice in the Mn-SOD antisense group survived longer (mean survival duration 94.4 +/- 12.7 days) compared to those in the empty vector group (67.3 +/- 6.8 days). After treatment with 5-FU (5 microg/day), PLM (50 microg/day), CDDP (10 microg/day) and gamma-rays (2 Gy/day), mean survival times were largely prolonged, to 126.3 +/- 22.7, 123.0 +/- 22.1, 136.3 +/- 24.0 and 143.0 +/- 20.8 days, respectively, while mean survival times in the empty vector group were 91.7 +/- 14.8, 85.7 +/- 13.3, 97.5 +/- 16.0 and 100.7 +/- 17.1 days, respectively. Immunohistologically, tumors in the Mn-SOD antisense group revealed additional nick end-labeled cells compared to those in the empty vector group. In comparison, strong expression of Bax, Bak and p21(waf1/cip1) and suppressed expression of Bcl-2, Bcl-X(L) and COX-2 were observed in the Mn-SOD antisense group and the expression pattern of these proteins was the inverse in the empty vector group. The increased expression of these proapoptotic proteins appeared to be p53-independent because p53 protein expression was not increased in the antisense group. These immunohistologic results were supported by Western blotting of each protein. In conclusion, Mn-SOD antisense transfection is advantageous for apoptosis induction of SCC cells by anticancer drugs and gamma-rays through induction of proapoptotic Bcl-2 family proteins and suppression of antiapoptotic protein expression.
Topics: Animals; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Apoptosis; Blotting, Western; Carcinoma, Squamous Cell; Cisplatin; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Cyclooxygenase 2; DNA, Complementary; Fluorouracil; Gamma Rays; Genetic Vectors; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Isoenzymes; Membrane Proteins; Mice; Mice, Nude; Neoplasm Transplantation; Oligonucleotides, Antisense; Peplomycin; Prostaglandin-Endoperoxide Synthases; Proto-Oncogene Proteins c-bcl-2; Reverse Transcriptase Polymerase Chain Reaction; Superoxide Dismutase; Time Factors; Transfection; Tumor Cells, Cultured; Up-Regulation
PubMed: 11745442
DOI: 10.1002/ijc.1513 -
Gynecologic and Obstetric Investigation 2001We presented a case of locally advanced cervical cancer treated by intraarterial infusion chemotherapy, and evaluated the blood flow of uterine arteries before and after...
We presented a case of locally advanced cervical cancer treated by intraarterial infusion chemotherapy, and evaluated the blood flow of uterine arteries before and after chemotherapy by using a transvaginal ultrasonic color Doppler device. Pulsatility index (PI) of each uterine artery increased after first course of chemotherapy compared to that of before chemotherapy. But PI did not change after second course in spite of a significant reduction in tumor size. Blood flow change assessed by Doppler ultrasound may be a limited but useful parameter for the efficacy of neoadjuvant chemotherapy in patients with cervical cancer.
Topics: Antineoplastic Combined Chemotherapy Protocols; Arteries; Chemotherapy, Adjuvant; Cisplatin; Female; Humans; Hysterectomy; Infusions, Intra-Arterial; Lymph Node Excision; Middle Aged; Mitomycin; Peplomycin; Pulsatile Flow; Ultrasonography, Doppler, Color; Uterine Cervical Neoplasms; Uterus
PubMed: 11729345
DOI: 10.1159/000052991