RESUMEN
PURPOSE OF INVESTIGATION: The study aimed to determine whether malignant transformation of mature cystic teratoma (MCT) can be preoperatively predicted by presenting two cases of MCT with malignant transformation and comparing their clinical factors with those of benign MCT encountered at around the same time. MATERIALS AND METHODS: Age, maximum tumor diameter, tumor marker levels (serum squamous cell carcinoma (SCC) and carbohydrate antigen (CA) 19-9, the presence of solid tumor masses, and the presence or absence of contrast enhancement in pelvic magnetic resonance imaging (MRI) were investigated in two cases of MCT with malignant transformation and 76 cases of benign MCT in which surgery was performed and a pathological diagnosis given by the department from 2004 to 2010. RESULTS: The mean ages of the two cases with malignant transformation and the cases of benign MCT were 42.5 years and 34.2 years, respectively. The mean maximum diameter of the two tumors with malignant transformation and the cases of benign MCT were 130 mm and 73.6 mm, respectively. The mean serum levels of SCC in the two cases with malignant transformation and the cases of benign MCT were 31.5 ng/ml and 0.92 ng/ml, respectively. Contrast enhancement and the presence of solid masses in images of MCT with malignant transformation were apparent. CONCLUSION: In order to accurately detect malignant transformation of MCT, the authors found it to be important to determine whether tumors larger than 100 mm in diameter were present and to check for the presence of solid masses enhanced in pelvic MRI examination, as well as to measure at least serum SCC and CA19-9 even in relatively young patients.
Asunto(s)
Transformación Celular Neoplásica , Neoplasias Ováricas/patología , Teratoma/patología , Adulto , Antígenos de Neoplasias/sangre , Antígeno CA-19-9/sangre , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/cirugía , Serpinas/sangre , Teratoma/diagnóstico , Teratoma/cirugíaRESUMEN
BACKGROUND: Small cell carcinoma of the uterine cervix is a rare cervical carcinoma that advances early and is associated with a poor prognosis. We present a case of this disease which invaded the parametrium and metastasized to the pelvic lymph node. The patient underwent postoperative concurrent chemoradiotherapy (CCRT) followed by maintenance chemotherapy and obtained long-term survival. CASE: A 26-year-old patient, who had conceived on two occasions without giving birth and had smoked for ten years, underwent radical hysterectomy with a diagnosis of Stage Ibl cervical carcinoma in December 2006. The patient showed parametrial invasion, and metastasis to the left external iliac node and vaginal stump. With a diagnosis of pT2bN1M0, the patient underwent CCRT with weekly nedaplatin as postoperative therapy. For the maintenance chemotherapy, from May 2007, ten courses of PE therapy (CDDP, 15 mg/body; VP-16, 100 mg/body x 3) were performed. No recurrent signs have been observed for 39 months after the first operation. CONCLUSION: PE therapy may be useful as maintenance therapy, although there are no established treatments for small cell carcinoma of the uterine cervix.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Pequeñas/tratamiento farmacológico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Adulto , Carcinoma de Células Pequeñas/mortalidad , Carcinoma de Células Pequeñas/patología , Cisplatino/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Estadificación de Neoplasias , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patologíaRESUMEN
PURPOSE: Photodynamic therapy (PDT) is a new approach to cancer treatment that utilizes photochemical reactions induced by a combination of an oncophilic photosensitizing agent and laser light. With an aim to apply PDT for intraperitoneal disseminated foci of advanced or recurrent ovarian cancers, the present study was conducted to evaluate the antitumor effect of PDT using a methyl ester of 5-aminolevulinic acid (Methyl-ALA) on various types of human ovarian cancer in a subcutaneous xenograft model in nude mice and to elucidate the mechanism of its antitumor effect. METHODS: HTOA, MCAS, and TOV21G cell lines derived from human ovarian serous, mucinous, and clear cell adenocarcinoma, respectively, were used in this study. The mice in the treatment group and in the control group received an intraperitoneal injection of 250 mg/kg of Methyl-ALA and PBS alone, respectively. PDT was administered by 10 min irradiation using a 150 W halogen light, 3 h after Methyl-ALA or PBS injection. Each mouse received PDT twice a week for 3 weeks. RESULTS: Methyl-ALA-PDT significantly suppressed the growth of HTOA tumors as compared to control, whereas there was no significant effect on the growth of MCAS or TOV21G tumors. Methyl-ALA-PDT significantly increased apoptosis in implanted HTOA tumors as well as cultured cells. Western blot analysis showed that amount of expression of milk fat globule-EGF-factor 8, which binds to apoptotic cells and thereby facilitates their phagocytosis, significantly increased in HTOA tumors receiving Methyl-ALA-PDT, compared with untreated HTOA tumors. In addition, reduced vascular endothelial growth factor and CD34-positive microvessel density were found in solid HTOA tumors treated by Methyl-ALA-PDT, suggesting that the antitumor effect of Methyl-ALA-PDT is due to induction of apoptosis and reduction of angiogenesis. In comparison with HTOA cells, HPLC analysis demonstrated a significantly smaller intracellular amount of protoporphyrin IX (PpIX) in MCAS and TOV21G cells. PpIX is readily converted from Methyl-ALA and elicts photocytotoxicity. CONCLUSION: We conclude that Methyl-ALA-PDT could be an effective treatment in ovarian cancer and should be tested to apply intraperitoneally disseminated micro-foci during surgery.
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Ácido Aminolevulínico/análogos & derivados , Neoplasias Ováricas/tratamiento farmacológico , Fotoquimioterapia/métodos , Adenocarcinoma/tratamiento farmacológico , Ácido Aminolevulínico/uso terapéutico , Animales , Apoptosis , División Celular/efectos de los fármacos , Línea Celular Tumoral , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Ratones Desnudos , Necrosis , Neoplasias Ováricas/patologíaRESUMEN
Few studies report on tissue morphology in recurrence of yolk sac tumor. The case of the recurrence of a yolk sac tumor as a spindle cell sarcoma of the abdominal wall is presented. A 27-year-old woman was referred to our hospital due to suspicion of an ovarian tumor. Right salpingo-oophorectomy, partial omentectomy, and extirpation of disseminated foci as fertility-preserving surgery was done since the intraoperative pathological diagnosis was yolk sac tumor. Final pathological examination showed a germ cell tumor of which yolk sac tumor formed the major component including a small area that appeared to be immature nerve tissue. Although residual tumor was not less than 1 cm, clinical complete remission was reached after the sixth course of BEP regimen. However, the recurrence of a yolk sac tumor as an unclassified spindle cell sarcoma of the abdominal wall was found about two years after the initial surgery. Thereafter, the patient expired due to progression of the intraperitoneal disseminated lesions. The mesenchyme-like component of the yolk sac tumor is characterized by spindle cells originating from epithelial elements, and is likely to give rise to a chemoresistant, diversely differentiated sarcoma. This report suggests that the sarcoma reported in the case here also arose when spindle cells of the mesenchyme-like component underwent sarcomatous change during or after chemotherapy, subsequently relapsed as a chemoresistant tumor, and metastasized.
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Neoplasias Abdominales/patología , Tumor del Seno Endodérmico/patología , Recurrencia Local de Neoplasia/patología , Sarcoma/patología , Neoplasias Abdominales/terapia , Pared Abdominal/patología , Adulto , Tumor del Seno Endodérmico/terapia , Resultado Fatal , Femenino , Humanos , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Sarcoma/terapiaRESUMEN
We examined pharmacokinetics of paclitaxel and carboplatin in a FIGO Stage IIIb ovarian cancer patient with hemodialysis-dependent chronic renal failure. The patient suffered from recurrence of the disease after treatment with optimal debulking surgery and postoperative chemotherapy consisting of cisplatin, epirubicin and cyclophosphamide, and she was treated with combined paclitaxel and carboplatin as second-line chemotherapy. The carboplatin dose was chosen to produce a target area under the concentration/time curve (AUC) of 5.0 microg-min/ml according to a published formula. Four-hour hemodialysis was started 24 hours and 16 hours after the end of carboplatin administration in the first and second courses of the chemotherapy, respectively. Pharmacokinetic studies showed that the AUCs of free platinum were 8.03 and 5.69 microg-min/ml in the first and second courses of the chemotherapy, respectively, suggesting that the AUC of carboplatin is affected by hemodialysis. However, an attenuation pattern of paclitaxel was almost similar between the first and the second courses, indicating that the change in blood concentration of paclitaxel was similar to that of patients with normal renal function. Hematological and nonhematological adverse effects were at an acceptable degree. The evidence suggests that even patients with chronic renal failure can undergo combination chemotherapy of paclitaxel and carboplatin without suffering any severe adverse effects by determining the time to start hemodialysis.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Neoplasias Ováricas/metabolismo , Diálisis Renal , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/farmacocinética , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/farmacocinéticaAsunto(s)
Butirilcolinesterasa/genética , Colitis Ulcerosa/enzimología , Mutación , Complicaciones del Embarazo/enzimología , Adulto , Butirilcolinesterasa/deficiencia , Femenino , Retardo del Crecimiento Fetal/diagnóstico , Retardo del Crecimiento Fetal/enzimología , Edad Gestacional , Humanos , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Polimorfismo Conformacional Retorcido-Simple , Embarazo , Resultado del EmbarazoRESUMEN
This is the first report on a syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) in a patient with recurrent ovarian cancer following carboplatin and paclitaxel administration. A 63-year-old woman received chemotherapy combining carboplatin and paclitaxel for recurrent ovarian serous papillary adenocarcinoma. Four days after the chemotherapy, she suffered decreased mental awareness and lost consciousness. Blood chemistry tests showed serum sodium of 109 mmol/l. Plasma osmolarity was reduced to 232 mOsm/kg while urine osmolarity was high at 430 mOsm/kg, strongly suggesting the presence of SIADH. Because hyponatremia was not observed in the subsequent cycle of chemotherapy consisting of weekly paclitaxel and cisplatin, carboplatin was thought to be responsible for the condition. Clinicians should be aware of the possibility that carboplatin may cause SIADH, and should carefully monitor electrolyte balance after chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Síndrome de Secreción Inadecuada de ADH/diagnóstico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Carboplatino/efectos adversos , Diagnóstico Diferencial , Femenino , Humanos , Síndrome de Secreción Inadecuada de ADH/sangre , Síndrome de Secreción Inadecuada de ADH/inducido químicamente , Persona de Mediana Edad , Paclitaxel/efectos adversosRESUMEN
Expression of cyclooxygenase (COX)-2 plays a key role in tumorigenesis and development and peroxisome proliferator-activated receptor gamma (PPARgamma) has been implicated in the control of COX-2 expression in some tissues. The aim of this study is to investigate (1) whether expression of COX-2 and PPARgamma is associated with ovarian carcinogenesis and progression of ovarian tumours and (2) whether COX-2 expression is controlled through ligand-mediated activation of PPARgamma in ovarian carcinoma cells. For this purpose, the presence of COX-2 and PPARgamma was immunohistochemically examined in 71 epithelial ovarian carcinomas, 18 borderline tumours and 23 benign tumours and the levels of COX-2 and PPARgamma proteins were determined by enzyme immunoassay in four benign tumours, three borderline tumours and 12 carcinomas. The frequency of COX-2 and PPARgamma detection was significantly increased and decreased as lesions progressed to carcinoma, respectively. The COX-2 protein was not detected in the three borderline tumours, whereas PPARgamma protein was detected in all of them. COX-2 protein was detected in eight of the 12 carcinomas, whereas PPARgamma protein was detected in only two cases. In addition, PPARgamma protein was not detected in all of the eight carcinomas in which COX-2 protein was detected, suggesting that expression of PPARgamma and COX-2 was in a reciprocal relationship. Furthermore, in cultured ovarian carcinoma cells, Western blot revealed that PPARgamma and COX-2 expression was regulated conversely as a result of stimulation by 15-deoxy-Delta(12, 14) PGJ(2) (15-PGJ(2)), a PPARgamma activator. In addition, 15d-PGJ(2) suppressed tumour necrosis factor-alpha-induced-COX-2 expression, confirming the reciprocal correlation between COX-2 and PPARgamma. From these results, it was suggested that PPARgamma activation might suppress COX-2 expression via the nuclear factor-kappaB pathway in the ovarian carcinoma cells and that low expression of PPARgamma and high expression of COX-2 might be involved in carcinogenesis and progression of ovarian tumours.
Asunto(s)
Adenocarcinoma/enzimología , Adenocarcinoma/patología , Transformación Celular Neoplásica , Cistadenocarcinoma Mucinoso/enzimología , Cistadenocarcinoma Mucinoso/patología , Regulación Neoplásica de la Expresión Génica , Isoenzimas/biosíntesis , Neoplasias Ováricas/enzimología , Neoplasias Ováricas/patología , Prostaglandina-Endoperóxido Sintasas/biosíntesis , Factores de Transcripción/farmacología , Adenocarcinoma/genética , Adulto , Anciano , Ciclooxigenasa 2 , Cistadenocarcinoma Mucinoso/genética , Proteínas de Unión al ADN , Femenino , Perfilación de la Expresión Génica , Humanos , Técnicas para Inmunoenzimas , Inmunohistoquímica , Ligandos , Proteínas de la Membrana , Microcuerpos , Persona de Mediana Edad , FN-kappa B/farmacología , Proteínas Nucleares , Neoplasias Ováricas/genética , Lesiones Precancerosas , Receptores Citoplasmáticos y Nucleares , Proteínas Represoras , Estudios Retrospectivos , Células Tumorales Cultivadas , Dedos de ZincRESUMEN
We present a patient with adenocarcinoma of the endometrial type mixed with a clear cell component (AMC) that metastasized to the vagina and one of the pelvic lymph nodes. She underwent a radical hysterectomy and pelvic and paraaortic lymphadenectomy, and then received postoperative adjuvant chemotherapy. Histologic features of the endometrial tumor included clear cell adenocarcinoma with an approximate 10% extent to endometrioid adenocarcinoma. On the other hand, histologic examination on the vaginal tumor predominatly showed clear cell adenocarcinoma and also revealed endometrioid adenocarcinoma to a very small extent, suggesting metastasis to the vagina from AMC. On immunohistochemical examination, expression of vascular endothelial growth factor (VEGF)-A, VEGF-C and VEGF-D was apparently stronger in the component of clear cell adenocarcinoma than in that of endometrioid adenocarcinoma. She has been a disease-free survivor for 26 months. Interestingly, locations of endometrial and vaginal lesions were consistent with the sites of an intrauterine device and ring pessary insertion, respectively.
Asunto(s)
Adenocarcinoma de Células Claras/secundario , Neoplasias Endometriales/patología , Neoplasias Vaginales/secundario , Adenocarcinoma de Células Claras/patología , Adenocarcinoma de Células Claras/cirugía , Anciano , Femenino , Humanos , Histerectomía , Escisión del Ganglio Linfático , Metástasis Linfática , Pelvis , Neoplasias Vaginales/patología , Neoplasias Vaginales/cirugíaAsunto(s)
Neumonía en Organización Criptogénica/diagnóstico , Complicaciones del Embarazo/diagnóstico , Adulto , Biopsia , Lavado Broncoalveolar , Broncoscopía , Cesárea , Neumonía en Organización Criptogénica/diagnóstico por imagen , Neumonía en Organización Criptogénica/patología , Diagnóstico Diferencial , Femenino , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Embarazo , Complicaciones del Embarazo/diagnóstico por imagen , Complicaciones del Embarazo/patología , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVES: In this study, we investigated the antiproliferative effect and telomerase activity of melatonin with or without cis-diamminedichloroplatinum (CDDP) on CDDP-sensitive HTOA cells and CDDP-resistant OVCAR-3 cells of cultured human ovarian cancer. METHODS: HTOA cells and OVCAR-3 cells were cultured in RPMI-1640 at 37 degrees C with 5% CO(2) for 132 h. To examine the antiproliferative effect of melatonin, cells were cultured with or without melatonin (10(-12)-10(-6) M) and thereafter counted in a 96-well microplate using the alamarBlue assay. To examine the effect of melatonin and CDDP, cells were divided into group A (intermittent CDDP, 0.5 microg/ml), group B (intermittent CDDP + melatonin), and group C (sequential (12-h interval) CDDP/melatonin) and thereafter counted in a 96-well microplate using the alamarBlue assay. In different series, cells were cultured and treated with either ethanol, melatonin, CDDP, or CDDP + melatonin. After harvest, telomerase activity was semiquantified with a fluorescence-based telomeric repeat amplification protocol (F-TRAP). RESULTS: (1) Melatonin produced no antiproliferative effect on both types of ovarian cancer cells. (2) Melatonin 10(-6) M induced the antiproliferative effect in groups B and C compared with group A in the HTOA cell line. (3) Melatonin 10(-9) M produced the antiproliferative effect in groups B and C compared with group A in the OVCAR-3 cell line. (4) Telomerase activity in the HTOA cell line did not change but, in the OVCAR-3 cell line, was significantly lower in the CDDP + melatonin group compared with the ethanol and CDDP groups. CONCLUSIONS: Melatonin enhanced CDDP sensitivity in two ovarian cancer cell lines. Thus, melatonin may improve ovarian cancer chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Cisplatino/farmacología , Melatonina/farmacología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , División Celular/efectos de los fármacos , Cisplatino/administración & dosificación , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Femenino , Humanos , Melatonina/administración & dosificación , Neoplasias Ováricas/enzimología , Telomerasa/metabolismo , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
The antitumor ribonucleoside analogue 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd), synthesized in 1995, has strong antitumor activity. In mouse mammary tumor FM3A cells, ECyd was rapidly phosphorylated to ECyd-triphosphate (ECTP) as the final product, strongly inhibiting RNA synthesis. The ultimate metabolite of ECyd, ECTP, is stable in cultured FM3A cells with a half-life of 21 hr; ECyd is on a "closed" metabolic pathway to ECTP. Deaminated ECyd derivatives were minor metabolites in the cells treated with Ecyd; therefore cytidine forms probably were not converted to uridine forms at the nucleoside or nucleotide stage. The characteristics of ECyd may be important for the antitumor activity. RNA polymerase in the nucleus was inhibited competitively by ECTP; the ki value was 21 nM. ECyd induced DNA and 28S ribosomal RNA fragnetations. The cleavage pattern of rRNA resembled in that mediated by RNase L. The results suggested that RNase L related mechanisms might be involved in the antitumor activity of ECyd.
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Antineoplásicos/farmacología , Citidina/análogos & derivados , Citidina/farmacología , Animales , Antineoplásicos/química , Apoptosis , Citidina/química , Endorribonucleasas/metabolismo , Ratones , Modelos Biológicos , ARN/biosíntesis , ARN Ribosómico/metabolismo , Células Tumorales CultivadasRESUMEN
BACKGROUND: International Federation of Gynecology and Obstetrics Stage I ovarian carcinoma, which has the worst prognosis among all types of gynecologic carcinoma, has a high cure rate as has been reported, but early diagnosis is difficult and to the authors' knowledge screening methods have not been established. Since 1989, the authors have performed transvaginal ultrasonography (TVS) as a form of screening for ovarian carcinoma. The purpose of the current study was to summarize and evaluate screening results for the last 10 years with respect to ovarian carcinoma diagnosis and risk factors. METHODS: Primary screening by TVS was performed in asymptomatic women who participated in annual uterine cervical carcinoma screening. Four scanning sections by TVS were established and all sonograms were recorded. Women with abnormal sonograms (a mass > 30 mm in greatest dimension or a mass with a mixed pattern) received secondary screening and closer examination with a tumor marker and an imaging diagnostic examination. Laparotomy was conducted on all masses with a greatest dimension of >/= 60 mm or on suspected malignant masses. Subject information-related risk factors also were recorded. RESULTS: Subjects were 183,034 women who participated in primary screening. Of these women, 51,550 were undergoing screening for the first time. The time required for primary screening was 1 minute per subject. Secondary screening was required for 5309 participants (10.3%) and surgery was performed on 324 participants. Twenty-two primary tumors and 2 metastatic tumors were detected for a diagnostic rate of 0.047%. Of the 22 primary tumors, 17 (77.3%) were classified as Stage I carcinoma, with tumor markers positive only for 5 (29.4%). The percentage of the total number of Stage I ovarian carcinoma cases increased after the induction of screening from 29.7% to 58.8%. CONCLUSIONS: These results are significant in that 77.3% of the primary ovarian carcinomas found during the current screening were of curable Stage I. Increased use of TVS screening for ovarian carcinoma may increase the chance for early diagnosis and decrease the mortality of the disease.
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Tamizaje Masivo , Neoplasias Ováricas/diagnóstico por imagen , Adulto , Anciano , Femenino , Humanos , Laparotomía , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/cirugía , Pronóstico , Estudios Prospectivos , Factores de Riesgo , UltrasonografíaRESUMEN
Although chemotherapy is indispensable for the treatment of ovarian cancer, secondary acute leukemia has become increasingly important as one of the most unfavorable late effects according to widespread long-term chemotherapy. We report a patient suffering from acute nonlymphocytic leukemia (ANLL) 3 years after treatment for stage IV ovarian cancer began.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cistadenocarcinoma Mucinoso/tratamiento farmacológico , Leucemia Mieloide Aguda/inducido químicamente , Neoplasias Ováricas/tratamiento farmacológico , Antibióticos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos Alquilantes/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Médula Ósea/patología , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Cistadenocarcinoma Mucinoso/secundario , Cistadenocarcinoma Mucinoso/cirugía , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Femenino , Humanos , Idarrubicina/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Persona de Mediana Edad , Mitoxantrona/uso terapéutico , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Prednisolona/uso terapéutico , Inducción de Remisión/métodos , ReoperaciónRESUMEN
OBJECTIVE: The aim of this study has been to evaluate the clinical significance of expression of VEGF and its receptors, Flt-1, KDR, and Flt-4, in endometrial carcinomas. METHODS: Specimens of endometrial carcinomas from 86 patients were investigated immunohistochemically using respective specific antibodies. Additionally, samples from 14 patients with complex atypical endometrial hyperplasia (AEH) and 15 patients with normal endometria were also examined. Immunohistochemical assessment was classified as negative, weakly positive, and strongly positive according to staining intensity and the percentage of positive cells. RESULTS: In positive cases, VEGF and its receptors were usually expressed homogeneously in the cytoplasms of cells in the endometrial carcimona, similar to the staining intensity of endothelial cells of stromal microvessels adjacent to carcinoma nests. The overall positive rates in the 86 carcinoma specimens were 66% for VEGF, 51% for Flt-1, 38% for KDR, and 57% for Flt-4. Their expressions in endometrial carcinoma tissues were high with significance or with borderline significance, compared to those in samples of complex AEH or normal endometria. Survival curves determined by the Kaplan-Meier method and univariate analysis showed VEGF, Flt-1, and Flt-4 overexpression to be related to poor prognosis of patients with endometrial carcinomas. However, multivariate analysis revealed that Flt-4 overexpression correlated independently with poor survival, similar to a value for myometrial invasion at one-half or more and that for retroperitoneal lymph node metastasis, whereas VEGF and Flt-1 overexpression did not. CONCLUSION: Flt-4 overexpression might be a promising prognostic indicator for survival of a patient with endometrial carcinoma.
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Biomarcadores de Tumor/biosíntesis , Carcinoma/metabolismo , Neoplasias Endometriales/metabolismo , Factores de Crecimiento Endotelial/biosíntesis , Linfocinas/biosíntesis , Neovascularización Patológica , Receptores de Factores de Crecimiento/biosíntesis , Adulto , Carcinoma/patología , Neoplasias Endometriales/patología , Endotelio Vascular , Femenino , Humanos , Inmunohistoquímica , Pronóstico , Análisis de Supervivencia , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
Metastasis of gastric cancer to the uterine cervix is rare, and a case of metastasis to the uterine cervix from early gastric cancer has never before been reported. We here present a patient who underwent a gastrectomy due to asymptomatic early gastric cancer found by chance and who subsequently suffered from a solitary metastasis to the uterine cervix from the primary early gastric cancer. Similar to Krukenberg tumors of the ovary, lymphatic dissemination is regarded as the route of metastasis from the stomach to the uterine cervix. We surmise that the present metastasis occurred through the lymphatic channel because lymph vessel permeations were found in both the primary lesion of the stomach and the metastatic lesion of the uterine cervix.
Asunto(s)
Adenocarcinoma/secundario , Neoplasias Gástricas/patología , Neoplasias del Cuello Uterino/secundario , Adenocarcinoma/patología , Adulto , Femenino , Humanos , Neoplasias Gástricas/cirugíaRESUMEN
We investigated the molecular mechanisms of cell death induced by 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd, TAS-106: Figure 1), a potent inhibitor of RNA synthesis, using mouse mammary tumor FM3A cells and human fibrosarcoma HT1080 cells. ECyd induced the characteristics of apoptosis on these cells, such as morphological changes, DNA fragmentations and caspase-3-like protease activation. General caspases inhibitor (Z-Asp-CH2-DCB) inhibited cell death. Interestingly, we also found that ECyd induced rRNA fragmentation with the size of 3.2, 2.8 and 1.5 kb, and which might be caused by inhibition of RNA synthesis. rRNA fragmentation was mainly occurred in D8 domain of 28 S rRNA, and the end of 5'-terminal sequence of 1.5 kb fragment was C3220pC3221p or C3221pG3222p, that was identical to the recognition sequence of RNase L. Furthermore, the fragmentation patterns of rRNA digested with RNase L resembled that of ECyd treated cells in shape. These results indicate that antitumor mechanisms of ECyd are involved in activation of RNase L. rRNA fragmentation may be one of the death events as a result of inhibition of RNA synthesis and play an important role in the antitumor activity of ECyd.
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Citidina/análogos & derivados , Citidina/farmacología , Inhibidores de la Síntesis del Ácido Nucleico/farmacología , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Endorribonucleasas/metabolismo , Activación Enzimática/efectos de los fármacos , Humanos , Ratones , ARN Neoplásico/metabolismo , ARN Ribosómico/metabolismo , Células Tumorales CultivadasRESUMEN
OBJECTIVES: To clarify the expression of multi-drug-resistant (MDR) markers, GST-pi, c-Jun, P-glycoprotein (Pgp), and MDR-associated protein (MRP) in epithelial ovarian cancer, and to determine whether their expression is predictive of chemotherapy response and patient prognosis. METHODS: Specimens of 58 epithelial ovarian cancer cases obtained at initial surgery were studied immunohistochemically using antibodies. RESULTS: Overall positive rates in the 58 specimens were 58.6% for GST-pi, 44.8% for c-Jun, 27.6% for Pgp, and 22.4% for MRP. The 5-year disease-free survival rate was 26.0% for patients with MRP-positive tumors and 75.2% for those with MRP-negative tumors. The prognosis for those with MRP-positive tumors was significantly poorer (p < 0.05). Patients with GST-pi-positive tumors had a significantly worse prognosis than those with GST-pi-negative tumors (51.9% vs 79.2%, p < 0.05). Multivariate analysis showed that residual tumors 2 cm or larger and MRP expression were independent prognostic factors for chemotherapy resistance. The relative risk of chemotherapy resistance in a patient with a residual tumor 2 cm or larger, positive MRP, and positive GST-pi was 10.6 times greater than the risk in a patient without these factors. CONCLUSION: MRP and GST-pi expression might be potential predictors of the response to standard chemotherapy in epithelial ovarian cancer. Their expression also might contribute to individualizing clinical trials of postoperative chemotherapy.
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Genes MDR/genética , Proteínas de Neoplasias/análisis , Neoplasias Ováricas/mortalidad , Antineoplásicos/uso terapéutico , Biomarcadores , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Japón/epidemiología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Valor Predictivo de las Pruebas , Estudios RetrospectivosAsunto(s)
Alcaligenes/enzimología , Desoxirribonucleasas de Localización Especificada Tipo II/metabolismo , Secuencia de Bases , ADN/metabolismo , Desoxirribonucleasas de Localización Especificada Tipo II/aislamiento & purificación , Concentración de Iones de Hidrógeno , Magnesio/metabolismo , Datos de Secuencia Molecular , Sodio/metabolismo , TemperaturaRESUMEN
The effect of ONO-3307 (4-sulfamoyl phenyl-4-guanidinobenzoate methanesulfonate), a new protease inhibitor, was studied on various proteases in vitro and in an experimental thrombosis model in vivo. ONO-3307 competitively inhibited trypsin, thrombin, plasma kallikrein, plasmin, pancreatic kallikrein and chymotrypsin; and their Ki values were 0.048 microM, 0.18 microM, 0.29 microM, 0.31 microM, 3.6 microM and 47 microM, respectively. In addition, ONO-3307 inhibited both elastase release from N-formyl-Met-Leu-Phe (fMLP)-stimulated leukocytes and tissue thromboplastin release from endotoxin-stimulated leukocytes. To examine the effects of ONO-3307 on disseminated intravascular coagulation (DIC), we developed an experimental thrombosis model. ONO-3307 (10 mg/kg/hr) completely inhibited the deposition of radioactive fibrin in kidney and lung. Gabexate mesilate (50 mg/kg/hr) was also effective in this model, but the effect of nafamostat mesilate was unclear. These results indicate that ONO-3307 exhibits a wide range of inhibitory effects on various proteases, and ONO-3307 may be useful for the treatment of protease-mediated diseases such as thrombosis and DIC.