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1.
OBJECTIVE: To determine prevalence and severity of carboplatin-induced dose-limiting toxicoses in the cat. ANIMALS: 9 healthy, 6- to 7-month-old cats weighing 4.7 (range, 3.0 to 6.5) kg. PROCEDURE: Cats were given a single i.v. bolus of carboplatin at a dosage of 150 (n = 3), 200 (n = 3), or 250 (n = 3) mg/m2 of body surface area. RESULTS: Dose-limiting neutropenia and thrombocytopenia were significant in all cats given carboplatin at 200 or 250 mg/m2. Weight loss, changes in appetite, and evidence of respiratory difficulty, as well as vomiting, diarrhea, or lethargy were not observed at any time during the 28-day period. At a highest dosage (250 mg/m2), the neutrophil nadir (560 +/- 303 neutrophils/microliters) was observed on day 17 and the platelet count nadir (96,500 +/- 11,815 platelets/microliters) was observed on day 14 after carboplatin administration. CONCLUSIONS: Carboplatin appears to be safe and clinically well-tolerated when given i.v. as a single bolus at a dosage of 200 mg/m2 to clinically normal cats. The dose-limiting toxicity of a single i.v. administered bolus is neutropenia. The nadir of a 200 mg/m2 i.v. administered dose occurs on day 17 (1,110 +/- 165 neutrophils/microliters) and neutropenia (< 2,000 neutrophils/microliters) lasts from day 14 through day 25 after carboplatin administration. CLINICAL RELEVANCE: The fatal dose-related pulmonary toxicosis observed in cisplatin-treated cats was inapparent in carboplatin-treated cats. To adequately determine the therapeutic role of carboplatin in tumor-bearing cats, a moderately tolerated dose of carboplatin of 200 mg/m2 given i.v. once every 4 weeks should be considered.  相似文献   

2.
TNP-470 (AGM-1470), a synthetic analog of fumagillin (6-chloroacetyl-carbamoyloxy-4-(1,2-epoxy-1,5-dimethyl- 4-hexenyl)-5-methoxy-1-oxaspiro [2,5] octane 1, has been reported to reduce the supply of nutrients to experimental tumors by inhibiting angiogenesis. In this study, we investigated anti-tumor activity of TNP-470 against human thyroid anaplastic carcinoma with a view to developing a new treatment for this thyroid tumor. A transplantable tumor was established from thyroid anaplastic carcinoma of a 78-year-old woman, as a xenograft in nude mice (BALB/c, nu/nu, male). This transplantable tumor, with chromosomal abnormality was shown to be non-functional in excretory hormones and to preserve morphological characteristics of the original anaplastic tumor tissue. TNP-470 was given at a dose of 50 mg/kg b.w. to nude mice transplanted with human thyroid anaplastic carcinoma by different routes of administration: intratumoral, peritumoral, subcutaneous and intraperitoneal. Intratumoral and peritumoral administration were effective, and especially the TNP-470 administered by the former route completely inhibited tumor growth. Immunohistochemical analysis using anti-factor VIII antibody revealed the density of microvessels to be significantly decreased by local administration of TNP-470 (intratumoral administration, 7.8 +/- 2.9/mm2, control, 27.0 +/- 6.3/mm2; peritumoral administration, 9.7 +/- 2.6/mm2, control, 21.1 +/- 5.1/mm2). Our findings suggested the possibility of clinical application of TNP-470 to control the growth of human anaplastic thyroid carcinoma.  相似文献   

3.
PURPOSE: To examine all basal cell carcinomas of the eyelid diagnosed in Iceland during a 25-year period, paying special attention to the surgical margins of excision in relation to recurrence. Based on the results a simple, clinically relevant method of classifying the surgical margin is proposed. METHODS: All histologically proven basal cell cancer specimens from eyelids were reviewed retrospectively. The surgical excision margins were classified as radical, marginal or intralesional. RESULTS: Recurrence risk was low when the tumor had a surgical margin described as radical or marginal. The recurrence rate was 38% when the margin was intralesional. CONCLUSION: By assessing the surgical margins by this method, which is easy to apply, better understanding between the pathologist and the surgeon may be achieved.  相似文献   

4.
The objective of this study is to evaluate the significance of intratumoral blood flow in ovarian cancer. Forty-seven patients with histologically proved ovarian cancer underwent transvaginal gray scale sonography, and color and Doppler sonography before surgery. Intratumoral blood flow velocity waveforms obtained from architecture within the tumor were recorded, and resistive index and peak systolic velocity were calculated. Neither resistive index values nor peak systolic velocity values differed significantly among the histological diagnoses, regardless of stage (including metastatic tumor) or morphologic classification of tumor. These results suggest that intratumoral blood flow analysis in ovarian cancer cannot provide information on individual tumor characteristics.  相似文献   

5.
Intratumoral injection of 90Y microspheres is a potential alternative in the treatment of primary liver tumor. However, complicated preparation and lack of a gamma ray for imaging are the disadvantages of 90Y. In this study, we used 188Re, a generator-produced radioisotope with 155-keV gamma ray emission, to label microspheres. After intratumoral injection of 188Re microspheres into rats with hepatoma, biodistributions and survival times were analyzed. METHODS: Twelve male rats with hepatoma were killed at 1, 24 and 48 hr (4 rats at each time point) after intratumoral injection of approximately 7.4 MBq 188Re microspheres. Samples of various organs were obtained and used to calculate the tissue concentrations. In addition, 30 male rats bearing hepatoma were divided into two groups (15 rats in each group) to evaluate survival time. Group 1 received intratumoral injection of 37 MBq 188Re microspheres, whereas Group 2 served as the control group and received an intratumoral injection of 0.1 ml normal saline only. Survival time was calculated from the day of injection to 2 mo after treatment. RESULTS: Radioactivity in the tumor was very high throughout. Biological half-time was 170.8 hr. Radioactivity in the lung was 1.78% injected dose (i.d.)/g at 1 hr but declined rapidly over time. The concentration in the urine was approximately 6.14% i.d./ml after the first hour and rapidly declined thereafter. The concentrations of radioactivity in other organs, such as normal liver, muscle, spleen, bone, testis and whole blood, were quite low throughout the study. Twelve of 15 (80%) of rats survived over 60 days after intratumoral injection of 188Re microspheres, whereas only 4 of 15 (26.7%) survived more than 60 days after injection of normal saline only. The difference between the groups was significant (p < 0.05). CONCLUSION: Rhenium-188 offers cost-effectiveness, on-site availability, short half-life, energetic beta particle, emission of gamma photons for imaging, easy preparation, easy clinical administration and apparent lack of radiation leakage from the treated tumor. Direct intratumoral injection of 188Re microspheres is extremely attractive as a clinical therapeutic alternative in hepatoma patients.  相似文献   

6.
OBJECTIVE: To analyze the expression of cathepsin (cath)-D and pro-cath-L in squamous cell carcinoma of the vulva and to determine whether those proteases have prognostic significance. STUDY DESIGN: Seventy-eight carcinomas were evaluated for tumor type, grade, inflammation and vascular space involvement. Formalin-fixed, paraffin-embedded tissue was stained for cath-D and pro-cath-L. Distribution, intensity and number of stained cells were examined and analyzed by the chi 2 test and receiver operator characteristic curves. RESULTS: Cath-D and pro-cath-L staining showed different distribution patterns. Cath-D expression at the tumor border was associated with development of recurrence (P = .018). Lymph node involvement was dependent on the staining patterns of cath-D and pro-cath-L. The number of pro-cath-L-positive cells correlated with the development of recurrence (P < .01). CONCLUSION: Protease expression of cath-D and pro-cath-L is localized in different tumor areas. The different staining patterns are associated with lymph node involvement and development of recurrence. The number of pro-cath-L-positive cells may be useful for predicting tumor recurrence.  相似文献   

7.
BACKGROUND: Squamous cell carcinomas of the head and neck (SCCHN), unlike normal mucosal squamous epithelial cells, overexpress epidermal growth factor receptor (EGFR) messenger RNA and protein. EGFR protein is required to sustain the proliferation of SCCHN cells in vitro. To determine whether EGFR expression contributes to tumor growth, we investigated the effect of suppressing EGFR expression in tumor xenografts through in situ expression of antisense oligonucleotides. METHODS: Intratumoral cationic liposome-mediated gene transfer was used to deliver plasmids capable of expressing sense or antisense EGFR sequences into human head and neck tumors, which were grown as subcutaneous xenografts in nude mice. The oligonucleotides were expressed under the control of the U6 RNA promoter. RESULTS: Direct inoculation of the EGFR antisense (but not the corresponding sense) plasmid construct into established SCCHN xenografts resulted in inhibition of tumor growth, suppression of EGFR protein expression, and an increased rate of apoptosis (programmed cell death). Sustained antitumor effects were observed for up to 2 weeks after the treatments were discontinued. CONCLUSION: These results suggest that interference with EGFR expression, using an antisense-based gene therapy approach, may be an effective means of treating EGFR-overexpressing tumors, including SCCHN.  相似文献   

8.
BACKGROUND: Although the anticancer effects of progesterone therapy for patients with endometrial carcinoma are widely acknowledged, a detailed assessment of the resultant morphologic alterations in tumor tissue kinetics has hitherto been lacking. METHODS: Biopsy and hysterectomy specimens of 14 endometrial carcinomas (endometrioid-type) before and during progesterone therapy were studied to clarify changes in apoptosis and cell proliferation and their relation to morphologic alterations. The extent of squamous differentiation within tumor lesions was also examined. RESULTS: In the good-response group, tumor cells took on characteristics of normal endometrial gland cells in the secretory phase. A positive correlation between reduction in the mitotic index and the degree of morphologic alterations during hormone therapy was observed, but the frequency of apoptotic cells did not vary. In both the good-response and poor-response groups, development or enlargement of squamous areas was observed, in comparison with the initial biopsy specimens. CONCLUSIONS: These results suggest that prolonged progesterone administration can suppress cell proliferation in endometrial carcinomas through tumor cell differentiation without altering apoptosis, resulting in a shift in tissue kinetics toward a relative predominance of cell deletion. In addition, increases in the occurrence of squamous areas within tumors do not always appear to be related to treatment efficacy.  相似文献   

9.
In the ICD-9 system, carcinomas of the nasal vestibule are classified together with carcinomas in the nasal cavity. As a rule, however, they are squamous cell carcinomas derived from the skin, and thus prognosis is better than in the case of squamous cell carcinomas derived from the mucosa of the nasal cavity. The article highlights essential features of brachytherapy. The authors present a critical assessment of the criteria for staging, and describe a specific patient material. Based on clinical experience and theoretical considerations, brachytherapy alone is recommended for T1-3 N0 tumours. In the case of T4 tumours external radiation therapy and brachytherapy combined is recommended for the primary tumour, with prophylactical irradiation towards regional lymph nodes.  相似文献   

10.
BACKGROUND: Malignant neoplasms of the paranasal sinuses are estimated at 3 to 5% of all head and neck malignant neoplasms. More than 50% of the cases are classified as squamous cell or anaplastic undifferentiated carcinomas. Extremely rare are small cell carcinomas localized in the paranasal sinuses. METHOD AND PATIENT: A 60-year-old male patient was seen in February 1996 in our ENT Department with unspecific pain on the left maxillary sinus and alveolar ridge. Anterior rhinoscopy revealed an extended tumor on the left nasal fossa; histopathological examination showed a small cell carcinoma. No other primary tumors or metastases were detected in extended staging. Due to the extended paranasal tumor as well as the histopathological findings, the patient was given induction chemotherapy followed by radiation therapy. RESULTS: To date (4/97), we achieved partial remission without any clinical complaints. CONCLUSIONS: The therapeutical result is comparable to other therapeutical regimens.  相似文献   

11.
Inverted papillomas in the nose and/or paranasal sinuses exhibit a high recurrence rate, and an association with malignancy. Early diagnosis and aggressive surgical therapy are thus essential. Seventeen cases of inverted papilloma seen at Saitama Cancer Center over a 17-year period were reviewed. Common presenting symptoms, the primary papilloma sites and the results of surgical treatment were as follows. 1) Almost all patients complained of nasal obstruction. The usefulness of nasal biopsy of the tumor was confirmed, with 12 cases being diagnosed as having inverted papilloma pre-operatively. Inverted papilloma without squamous cell carcinoma caused osseous thinning, but did not destroy the bone. 2) It was found that the primary site of the papilloma involved the lateral wall of the nasal cavity. Lateral Rhinotomy was therefore recommended as a standard treatment. 3) The recurrence rate was 1/12 after Lateral Rhinotomy. Two cases had complaints associated with the Lateral Rhinotomy, nasolacrimal duct stenosis, and a scar in the median corner of eye. 4) Only one case had concomitant squamous cell carcinoma in the nose and maxillary sinus. This patient received chemo therapy, radiation therapy and finally maxillectomy, but the inverted papilloma recurred several times. Six years later, squamous cell carcinoma recurred and lead to this patient's death.  相似文献   

12.
OBJECTIVES: Tumor suppressor gene mutations in both p53 and PTEN/MMAC1 genomic DNA have been detected in many types of cancer. The purpose of this study was to investigate the presence and importance of PTEN/MMAC1 mutations in squamous cell carcinomas. METHODS: Exons of each gene were amplified after polymerase chain reaction (PCR) using genomic DNA derived from cell lines of squamous cell carcinoma of the head and neck (SCCHN) and snap-frozen biopsy specimens from primary established head and neck tumors. The amplified and purified DNA was then sequenced directly. RESULT: As anticipated, point mutations of the p53 gene were found in 80% of cell lines examined. A single base mutation in codon 151 was found in six of 10 cell lines studied. PTEN/MMAC1 gene mutations were found in neither the cell lines tested nor the tumor biopsy samples. CONCLUSION: This study, as well as a large volume of data, confirms that mutations of the p53 gene are frequent events in head and neck cancer cell lines. Although PTEN/MMAC1 gene mutations have been found in a variety of carcinomas, this gene was not found to be mutated in SCCHN cell lines or in primary squamous cell carcinomas of the head and neck. This information is useful for further studies of mutations in these cell lines.  相似文献   

13.
Although it is well-known that cancers show intratumoral phenotypic heterogeneity, genotypic studies have been scarce. Using comparative genomic hybridization and laser scanning cytometric analyses, we investigated intratumoral cytogenetic heterogeneity in 21 surgically removed gliomas including 11 glioblastomas (GBMs), 8 anaplastic astrocytomas (AAs) and 2 low-grade astrocytomas. Comparative genomic hybridization analysis revealed gain or amplification of 7p in 63%, gain of 7q in 73%, loss of 9p in 53%, loss of 10p in 47%, loss of 10q in 47%, loss of 13q in 53%, and loss of 22q in 37% of high-grade astrocytomas. Because these aberrations were region-independent within the same tumor, they did not contribute to intratumoral cytogenetic heterogeneity. Such heterogeneity was due to cytogenetic changes other than the above region-independent aberrations. Intratumoral cytogenetic heterogeneity was detected in 8 of 11 GBMs, 4 of 8 AAs, and none of the 2 low-grade astrocytomas. These observations suggest that cytogenetic changes at chromosomes 7, 9p, 10, 13, and 22 are primary events in high-grade astrocytomas and that subsequent cytogenetic changes involving increases in copy number provide intratumoral heterogeneity. DNA aneuploidy was detected by laser scanning cytometry in 5 of 11 GBMs and 1 of 8 AAs. All tumors with DNA aneuploidy exhibited intratumoral cytogenetic heterogeneity, and there was a significant correlation between DNA aneuploidy and intratumoral cytogenetic heterogeneity. These results support the notion that cytogenetic heterogeneity results from genetic instability within a tumor.  相似文献   

14.
The oil bodies of plant seeds contain a triacylglycerol matrix surrounded by a monolayer of phospholipids embedded with alkaline proteins termed oleosins. Two distinct oleosins are present in the oil bodies of diverse angiosperms, and classified as high and low Mr isoforms according to their relative molecular masses in each species. In sesame oil bodies, besides the two ubiquitous oleosin isoforms (17 and 15 kDa), an additional minor oleosin (15.5 kDa) was revealed on Tricine SDS-PAGE. A full-length cDNA fragment was cloned, sequenced and deduced to be a putative oleosin of 15,446 Da. The gene was constructed in a fusion or non-fusion vector and then over-expressed with different efficiency in Escherichia coli. All three oleosins purified from sesame oil bodies were subjected to immunoassaying using antibodies raised against the over-expressed oleosin. The results confirmed that this gene encodes the sesame 15.5 kDa oleosin. Sequence comparisons with other known oleosins revealed that sesame 15.5 kDa oleosin does not represent a new oleosin isoform class but may have been derived through gene duplication and truncation of sesame 17 kDa oleosin, and possesses the minimal structure of the high Mr oleosin isoform. A conserved amphipathic alpha-helix is predicted in sesame 15.5 kDa oleosin, which may imply a potential biological function associated with this isoform.  相似文献   

15.
BACKGROUND: The lithium salt of gamma-linolenic acid (Li-GLA) is growth inhibitory to pancreatic cancer cells in vitro and is reported to prolong the survival of patients with pancreatic cancer. The effect of Li-GLA on the growth of human pancreatic carcinoma in vivo is not known. In this study the effect of parenterally administered Li-GLA on the growth of human pancreatic carcinoma in nude mice was tested. METHODS: Pancreatic tumours were produced in nude mice by subcutaneous implantation of MIA PaCa-2 cells. This cell line is sensitive to Li-GLA in vitro. Mice were randomly treated with intraperitoneal, intravenous or intratumoral Li-GLA. Each group also had controls. RESULTS: Both intravenous and intraperitoneal administration of Li-GLA had no significant effect on tumour growth or tumour phospholipid fatty acid composition. Intratumoral administration of Li-GLA was, however, associated with a significant antitumour effect. CONCLUSION: Within the limitations of this tumour model, the benefit seen with intravenous Li-GLA in patients with pancreatic carcinoma cannot be explained by tumour growth inhibition. Local administration appears to be more effective than intravenous or intraperitoneal therapy.  相似文献   

16.
PURPOSE: To determine the appropriate radiation therapy and chemotherapy for primary lymphoma of the nasal cavity to improve the local control and survival rates. MATERIALS AND METHODS: Of the 25 adult patients with stage IE nasal lymphoma, nine underwent local radiation therapy alone and 16 underwent radiation therapy and chemotherapy (intravenous infusion). Radiation doses to the involved area were 22-54 Gy (median dose, 49 Gy). RESULTS: The 5- and 10-year cause-specific survival rates were 91% and 73%, respectively. The 5- and 10-year disease-free survival rates were 83% and 59%, respectively. Eight patients developed recurrent disease: six at the local site, one in the cervical nodes, and one in the small intestine. Five of the six patients with local recurrence received less than 50 Gy. Four of the six patients developed recurrent disease in the treated area; the other two patients developed marginal recurrences. Prognostic factors such as age, sex, maximum tumor size, and lactate dehydrogenase level were of limited value. CONCLUSION: The most common recurrence site was the local site. To improve the local control rate, the involved area should be treated with high-dose radiation therapy. The clinical results did not demonstrate the usefulness of combination chemotherapy for stage IE nasal lymphoma.  相似文献   

17.
Papillary carcinomas of the uterine cervix with transitional or squamous differentiation are rare tumors that often resemble transitional cell carcinomas of the urinary tract. We reviewed 32 such cases of papillary cervical carcinoma and divided them into three groups: 1) predominantly (> 90%) squamous (nine cases), 2) mixed squamous and transitional (16 cases), and 3) predominantly transitional (seven cases). Overall, the patients ranged in age from 22 to 93 years (mean 50), and the most common clinical presentation was abnormal bleeding (15 patients) and an abnormal Papanicolaou smear (nine patients). The tumors ranged in size from 0.7 to 6.0 cm (mean 3.0). All cases demonstrated a papillary architecture with fibrovascular cores lined by a multilayered, atypical epithelium resembling a high-grade squamous intraepithelial lesion of the cervix. Underlying superficial to deep stromal invasion was seen in 18 of 20 cases (90%); in the remaining 12 cases, the specimen was too superficial to assess invasion. Eighteen (86%) of the 21 cases examined immunohistochemically demonstrated immunoreactivity for cytokeratin 7, whereas only two of the 21 (9.5%) showed positivity for cytokeratin 20. Of the 12 women for whom follow-up information was available, three were treated by simple hysterectomy, two underwent radical hysterectomy, one was treated with radiation alone, and one with combination chemotherapy and radiotherapy. Three patients died of disease (two in the squamous group and one transitional) within an average of 13 months after diagnosis. Local recurrence developed in two women, and one of these, a vaginal recurrence, occurred 12 years after the original diagnosis. Based on the above findings, we believe that these tumors are a clinicopathologically distinct, homogeneous group that display a morphologic spectrum. Nevertheless, because some tumors may show a purely squamous or purely transitional appearance, we propose retaining the above three separate designations for these tumors with the understanding that there is often a substantial degree of subjectivity in deciding whether a tumor is squamous or transitional. The most distinctive, objective, and easily recognizable feature of these tumors is their surface papillary architecture rather than their superficial resemblance to transitional cell carcinomas of the urinary tract, and we emphasize the need to distinguish these potentially aggressive malignant tumors from the far more common and benign papillary lesions of the cervix.  相似文献   

18.
The carcinogenic effects of diisopropanolinitrosamine (DIPN) were tested in Sprague-Dawley rats and were then compared with results produced earlier by the same substance in Syrian hamsters. In addition to the similarities, several differences were noted; for example, DIPN caused pancreatic tumors in all the hamsters, but only 1 pancreatic tumor was observed among the 150 rats. Administration of DIPN to rats led to the development of neoplasms in the nasal and paranasal cavities, lungs, thyroid gland, esophagus, liver, and kidneys. The highest tumor incidence in rats was in the nasal cavities. Almost all the pulmonary neoplasms were malignant and were usually squamous cell carcinomas. We found a 15.4-50% incidence of malignant tumors of the thyroid gland; we also noted that thyroid neoplasms occurred at almost the same rate (36.4-50%) in the groups given 1/5, 1/10, and 1/20 the median lethal dose.  相似文献   

19.
Three hundred cases of primary neoplasms involving the nasal cavity or paranasal sinuses were found among the reports of 12,300 microscopically confirmed neoplasms. The multispecies data were compiled from abstracts of medical records by 13 colleges of veterinary medicine in the United States and Canada from 1964 to 1973. Significant numbers of neoplasms were observed in dogs, horses, and cats. Intranasal neoplasms were more frequent than those of the paranasal sinuses in dogs and cats. Only cats had a sex difference in the occurrence of nasal neoplasms, with a male predilection. The frequency of neoplasms of the nasal cavity and paranasal sinuses increased with age in all species examined. A clear relationship could not be established between nose length and of intranasal neoplasms. Of the tumors, 80% were malignant in dogs, 68% in horses, and 91% in cats. Detailed review of medical records in a subset of 49 dogs with neoplasms of the nasal passage and paranasal sinuses revealed major clinical signs of nasal and ocular discharge, facial deformity, and stertorous breathing. Median duration of signs prior to diagnosis was 3 months and 95% of the dogs had been given treatment prior to definitive diagnosis. All 49 tumors were malignant; 27 were classified histologically as carcinomas and 22 were sarcomas. Nineteen dogs were treated, using surgery alone or in combination with radiation therapy. Median survival duration was 5 months (mean 6.7 mo).  相似文献   

20.
A phase II study was conducted to evaluate the activity of paclitaxel and carboplatin in advanced head and neck cancer. Twenty-four patients with measurable locoregional squamous cell carcinoma and metastatic disease were entered. All had been heavily pretreated with radiotherapy, surgery and chemotherapy and were at second recurrence or disease progression when they entered the trial. Patients received Paclitaxel 200 mg/m2 with carboplatin 7 AUC once every 3 weeks with premedication with dexamethasone and diphenyldramine and ranitidine. Twenty-three patients were evaluable for response. Four patients (17%) achieved a complete response and 5 (22%) a partial response for an overall response rate of 39%. Duration of response was 3-9 months. Toxicity was tolerable. Four patients showed Grade III (WHO) and 6 Grade II neutropenia. Nineteen (79%) of patients who received more than two courses of chemotherapy presented neurotoxicity. The combination of paclitaxel and carboplatin was effective in heavily pretreated patients with squamous cell carcinoma of the head and neck.  相似文献   

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