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Japanese Journal of Radiology Jan 2012The aim of this study was to investigate the role of the combined use of customized molds and a high dose rate (HDR) remote afterloading brachytherapy apparatus with a...
PURPOSE
The aim of this study was to investigate the role of the combined use of customized molds and a high dose rate (HDR) remote afterloading brachytherapy apparatus with a (192)Ir microsource in the treatment of superficial oral carcinomas after chemoradiotherapy.
MATERIALS AND METHODS
Nine patients with oral squamous cell carcinoma who were treated using this combined technique were analyzed retrospectively. The primary sites of the tumors were the mouth floor, gingiva, and soft palate. For each patient, a customized mold was fabricated in which 2-3 afterloading catheters were placed for the (192)Ir source. Three to eight fractions of 3 Gy, 5 mm below the mold surface, were given following external radiotherapy of 24-50 Gy/2 Gy combined with chemotherapy (peplomycin or taxotere). The total dose of HDR brachytherapy ranged from 9 to 24 Gy.
RESULTS
The 2-year local control probability was 100% and the 2-year cause-specific survival rate was 100%. No serious complications (i.e., ulcer or bone exposure) have been observed thus far during the follow-up period of 29-120 months.
CONCLUSION
HDR brachytherapy using the mold technique after chemoradiotherapy is a safe and excellent method for selected early and superficial oral cavity cancers.
Topics: Adult; Aged; Aged, 80 and over; Brachytherapy; Carcinoma, Squamous Cell; Catheterization; Chemoradiotherapy; Female; Follow-Up Studies; Humans; Iridium Radioisotopes; Male; Mouth Floor; Mouth Neoplasms; Radiotherapy Dosage; Radiotherapy, Adjuvant; Radiotherapy, Computer-Assisted; Retrospective Studies; Survival Rate
PubMed: 22160650
DOI: 10.1007/s11604-011-0005-z -
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 -
The Journal of Antibiotics Apr 2011¹H-NMR spectra of peplomycin (PEP) recorded at 400 and, for the first time, 900 MHz at 2 °C were examined. All the spin systems in the PEP molecule were identified...
¹H-NMR spectra of peplomycin (PEP) recorded at 400 and, for the first time, 900 MHz at 2 °C were examined. All the spin systems in the PEP molecule were identified through 2D NMR spectroscopy. The use of NMR spectroscopy allowed the unambiguous assignment of 62 protons, generating 47 non-exchangeable and 15 exchangeable signals. The analysis of the signals observed in 2D-NOE spectra indicates that PEP exhibits an extended conformation at 2 °C. A comparison between the solution conformation of apo-PEP and the solution structure of HOO-Co(III)-PEP indicates that the overall structure of apo-PEP is extended in solution, but exhibiting a conformation of the bithiazole (B)-sulfonium (S) unit similar to that of HOO-Co(III)-PEP. The present investigation represents the initial stage of an NMR study of the solution conformation and dynamics of PEP, its derivatives, its metal complexes and the interactions of metallo-PEPs with their target DNA.
Topics: Antibiotics, Antineoplastic; DNA; Magnetic Resonance Spectroscopy; Metals; Peplomycin; Solutions
PubMed: 21326254
DOI: 10.1038/ja.2010.163 -
Histochemistry and Cell Biology Jan 2011Peplomycin (PEP), an anti-tumor antibiotic related structurally to bleomycin, is widely used, especially for squamous cell carcinoma but shows renal toxicity. We...
Peplomycin (PEP), an anti-tumor antibiotic related structurally to bleomycin, is widely used, especially for squamous cell carcinoma but shows renal toxicity. We prepared monoclonal antibodies (mAbs) against N-(γ-maleimidobutyryloxy)succinimide-conjugated PEP. The mAbs were monospecific for PEP, but did not react with bleomycin and other anticancer antibiotics. The mAbs enabled us to develop an immunocytochemical (ICC) method for detecting the uptake of PEP in the rat kidney. Two hours after a single i.v. administration of PEP, ICC revealed immunostaining for PEP in irregularly shaped cytoplasmic granules of the proximal tubules in which the microvilli were also stained. Also, staining occurred in the distal tubules and collecting ducts, in both of which we observed scattered swollen cells, reminiscent of necrotic cells, in which both the nuclei and cytoplasm reacted strongly with the antibody. Twenty-four hours after injection, PEP in the proximal tubules completely vanished, but yet significant amounts of PEP remained in both the distal tubules and collecting ducts. Distribution patterns of PEP in cells of the kidneys resembled, in some ways, those of our recent ICC studies for an organic cation aminoglycoside antibiotic gentamicin. This ICC suggests that PEP taken up in the proximal tubule cells is localized in the lysosomes, and organic cation transporters and bleomycin hydrolase might be involved in entrance and/or disappearance of PEP in this cell type. Furthermore, the distal tubules and collecting ducts may be the sites readily affected by some chemotherapeutic agents.
Topics: Animals; Antibiotics, Antineoplastic; Antibodies, Monoclonal; Enzyme-Linked Immunosorbent Assay; Humans; Immunohistochemistry; Kidney; Male; Mice; Peplomycin; Rats; Rats, Wistar
PubMed: 21153656
DOI: 10.1007/s00418-010-0768-9 -
Journal of UOEH Jun 2010Cutaneous squamous cell carcinoma (SCC) frequently metastasizes to lymph nodes, but metastasis to the spine is rare. We report a case of cutaneous SCC with metastasis to...
Cutaneous squamous cell carcinoma (SCC) frequently metastasizes to lymph nodes, but metastasis to the spine is rare. We report a case of cutaneous SCC with metastasis to a particularly rare region, the thoracic spine, which evolved into a spinal cord compression. In November 2005, a 73-year-old man underwent a resection of a primary tumor and standard inguinal lymphadenectomy for a cutaneous SCC of the right fourth toe, defined as T2N1M1 stage. Over the next 3 years, he was given peplomycin, CAV (cisplatin, adriamycin, and vindesine) therapy and radiotherapy for multiple lymph node metastases. In September 2008, he complained of back pain and urinary retention. Magnetic resonance imaging of the thoracic spine showed the presence of masses in the vertebral body, which compressed the spinal cord. Blood examination revealed an elevated level of serum SCC antigen. After irradiation and chemotherapy, the patient's complaint was relieved and the level of serum SCC antigen concomitantly declined. Spinal metastasis is one of the items to be kept in mind during the follow-up of patients with cutaneous SCC.
Topics: Aged; Carcinoma, Squamous Cell; Combined Modality Therapy; Humans; Lymphatic Metastasis; Male; Skin Neoplasms; Spinal Cord Compression; Spinal Neoplasms; Thoracic Vertebrae; Urinary Retention
PubMed: 20549904
DOI: 10.7888/juoeh.32.155 -
Archives of Gynecology and Obstetrics Nov 2009The management of ovarian cancer during pregnancy represents a major challenge and requires close multidisciplinary team approach.
BACKGROUND
The management of ovarian cancer during pregnancy represents a major challenge and requires close multidisciplinary team approach.
CASE
A 35-year-old pregnant woman with a yolk sac tumor underwent left salpingo-oophorectomy at 25 weeks of gestation. Chemotherapy was deferred to the end of the pregnancy owing to concerns for potential fetal risks. Alpha-feto protein level was used to monitor the underlying disease activity. The patient underwent exploratory laparotomy with cesarean section followed by total hysterectomy, omentectomy, right salpingooophorectomy, pelvic, and para-aortic lymphadenectomies at 32 weeks of gestation. She received four postoperative courses of chemotherapy (cisplatin, etoposide, and peplomycin). Currently, mother and child are doing well 6 months after the last chemotherapy cycle.
CONCLUSION
In a case of yolk sac tumor in the second trimester of pregnancy, radical surgery combined with elective caesarian section followed by chemotherapy could achieve remission and rescue of fetus. However, the treatment needs to be individualized as there is lack of evidence.
Topics: Adult; Antineoplastic Agents; Cesarean Section; Endodermal Sinus Tumor; Female; Histocytochemistry; Humans; Hysterectomy; Infant, Newborn; Ovarian Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Trimester, Second; alpha-Fetoproteins
PubMed: 19234710
DOI: 10.1007/s00404-009-0977-4 -
Oral Oncology Sep 2009The presence or absence of metastasis bears an important influence on the prognosis of head and neck cancer patients. Neoadjuvant chemotherapy has become widely employed...
The presence or absence of metastasis bears an important influence on the prognosis of head and neck cancer patients. Neoadjuvant chemotherapy has become widely employed as an initial treatment. However, the actual effectiveness of neoadjuvant chemotherapy on metastasis is still unestablished. Therefore, using an orthotopic implantation model in which cervical lymph node metastasis of oral squamous cell carcinoma can be reproduced, we investigated the inhibitory effect of neoadjuvant chemotherapy on metastasis. A highly invasive and metastatic human oral squamous cell carcinoma cell line, OSC-19 cells, was implanted into the tongues of nude mice. After implantation, the mice were divided into four groups: S (surgery), C+S (preoperative chemotherapy+surgery), S+C (surgery+postoperative chemotherapy), and a control (nontreatment) groups. The treatment (tumor resection or chemotherapy) was started 7 days postimplantation. The effects of each treatment on cervical lymph node metastasis were investigated by examining the rate of lymph node metastasis formation at 28 days postimplantation. In the control group, five of the 11 mice died of cachexia before the end of the experiment. However, all mice in the S, C+S, and S+C groups survived until 28 days after implantation. The cervical lymph node metastasis rates were 81.8% in S, 18.1% in C+S, 63.6% in S+C, and 100% in control groups. Thus, metastasis to the cervical lymph node was markedly inhibited by the combination of neoadjuvant chemotherapy and tumor resection. The findings of this study indicate that neoadjuvant chemotherapy is effective for inhibiting metastasis, and that it is necessary to begin chemotherapy as early as possible to achieve an inhibitory effect on metastasis. Considering these effects, if anticancer drugs are used, better therapeutic results can be expected.
Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Carcinoma, Squamous Cell; Cisplatin; Disease Models, Animal; Female; Humans; Lymphatic Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; Neck; Neoadjuvant Therapy; Peplomycin; Tongue Neoplasms; Treatment Outcome
PubMed: 19200774
DOI: 10.1016/j.oraloncology.2008.12.003 -
Ai Zheng = Aizheng = Chinese Journal of... Sep 2008Cervical adenosquamous carcinoma is a special histological type of cervical carcinoma. Its clinic-pathologic characteristics and prognostic factors have seldom been...
BACKGROUND & OBJECTIVE
Cervical adenosquamous carcinoma is a special histological type of cervical carcinoma. Its clinic-pathologic characteristics and prognostic factors have seldom been reported. This study was to explore the clinic-pathologic characteristics and prognostic factors of cervical adenosquamous carcinoma.
METHODS
Clinical data of 83 pathologically confirmed adenosquamous cervical carcinoma patients in Sun Yat-sen University Cancer Center from Nov. 1982 to May 2006 were analyzed.
RESULTS
The median overall survival (OS) of 83 patients was 47 months and the median disease-free survival was 43 months. The 5-year survival rate was 74.0%, and the recurrence rate (DFS) was 30.1% (25/83). The median OS and DFS were 58 months and 54 months versus 37 months and 21 months in patients with or without lymph node metastasis (P=0.005, P<0.001). The median DFS was 47 months and 16 months for patients with the tumor diameter >4 or < or =4 cm (P=0.015), respectively. Lymph node metastasis was correlated to FIGO stage, tumor diameter and invasion depth. The recurrence rate of patients with ovarian preservation was 33.3% (3/9).
CONCLUSIONS
Lymph node metastasis is an independent risk factor for prognosis in cervical adenosquamous carcinoma. Adjunctive postoperative irradiation would improve the OS and DFS. Tumor diameter greater than 4cm is an independent prognostic risk of DFS. The impact of ovarian preservation on prognosis is unclear.
Topics: Aclarubicin; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Carcinoma, Adenosquamous; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Female; Follow-Up Studies; Humans; Hysterectomy; Lymphatic Metastasis; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Peplomycin; Prognosis; Proportional Hazards Models; Radiotherapy, Adjuvant; Survival Rate; Tumor Burden; Uterine Cervical Neoplasms
PubMed: 18799035
DOI: No ID Found -
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 -
Oncology Reports Jul 2008Minimal optimal surgery without chemotherapy is often performed for patients with ovarian immature teratoma, which frequently occurs in young women who hope for future...
Minimal optimal surgery without chemotherapy is often performed for patients with ovarian immature teratoma, which frequently occurs in young women who hope for future pregnancies. If tumors recur after the operation, anticancer drug chemotherapy is often administered, although few studies have highlighted differences between the recurrent and the primary tumor cells. Therefore, we have established experimental animal models of recurrent ovarian immature teratoma cells after optimal surgery and characterized the anticancer drug sensitivity and antigenicity of the recurrent tumors. Surgically-excised tumor cells of a grade II ovarian immature teratoma were cultured in vitro and transplanted into nude mice to establish stable cell lines. Differential drug sensitivity and antigenicity of the tumor cells were compared between the primary and the nude mouse tumors. Nude mouse tumor cells showed a normal 46XX karyotype. Cultured primary cells showed a remarkably high sensitivity to paclitaxel, docetaxel, adriamycin and pirarubicin, compared to peritoneal cancer cells obtained from a patient with ovarian adenocarcinomatous peritonitis. The drug sensitivity of teratoma cells to 5-fluorouracil, bleomycin or peplomycin was also significantly higher. However, there was no significant difference in sensitivity to platinum drugs between the primary teratoma and the peritoneal adenocarcinoma cells. As for nude mouse tumor cells, sensitivity to 12 anticancer drugs was significantly lower than that of the primary tumor cells, while there was little difference in sensitivity to carboplatin or peplomycin between the primary and nude mouse tumor cells. Flow cytometry showed that the expression of smooth muscle actin (SMA) significantly decreased in nude mouse tumor cells when compared to cultured primary cells. In conclusion, ovarian immature teratomas with normal karyotypes have a malignant potential to recur after minimal surgery. During nude mouse transplantation, SMA-overexpressing cells appeared to be selectively excluded and nude mouse tumor cells were less sensitive to the majority of anticancer drugs than the primary tumor cells. These results indicate that after optimal surgery for ovarian immature teratoma, recurrent cells can be more resistant to anticancer drugs than the primary tumors. Therefore, it is likely that adjuvant chemotherapy lowers the risk of ovarian immature teratomas recurring after optimal surgery. BEP and PBV regimens are frequently given to teratoma patients. However, paclitaxel/carboplatin or docetaxel/carboplatin, which are the most effective chemotherapy treatments for epithelial ovarian cancer patients, are considered to be an alternative regimen, especially in the prevention of reproductive toxicity.
Topics: Adolescent; Animals; Cell Line, Tumor; Drug Screening Assays, Antitumor; Female; Flow Cytometry; Humans; Karyotyping; Mice; Neoplasm Recurrence, Local; Ovarian Neoplasms; Teratoma
PubMed: 18575713
DOI: No ID Found