RESUMO
We previously reported that introduction of the wild-type p53 gene into human cancer cells with deleted p53 enhanced apoptosis induced by chemotherapy [Fujiwara et al. (1994) Cancer Res 54:2287]. This suggests that p53 status could be a potent determinant of the therapeutic efficacy of DNA-damaging cancer therapy. We analyzed 24 patients with gastric or colorectal cancer for p53 mutations and apoptotic changes in surgical specimens. Out of 11 patients with gastric cancer, 3 were treated with chemotherapeutic drugs before resection; 5 of 13 patients with colorectal cancer had 30 Gy radiation prior to surgery. p53 mutations were detected in 4 cases of gastric cancer (36.4%) and in 6 cases of colorectal cancer (46.2%) by immunohistochemical staining. The preoperative DNA-damaging therapies increased the number of apoptotic cells in wild-type-p53-expressing tumors; tumors with mutant p53, however, significantly showed fewer apoptotic cells compared with those expressing wild-type p53. The p53-inducible WAF1/CIP1 protein was immunohistochemically observed in wild-type-p53-containing tumors, whereas mutant-p53-expressing tumors expressed no detectable WAF1/CIP1. Taken together, we conclude that p53 mutations are associated with the poor response of chemotherapy and radiotherapy.
Assuntos
Neoplasias do Colo/genética , Neoplasias do Colo/terapia , Genes p53 , Tolerância a Radiação , Neoplasias Retais/genética , Neoplasias Retais/terapia , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Apoptose/efeitos da radiação , Neoplasias do Colo/patologia , Terapia Combinada , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/análise , DNA de Neoplasias/análise , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias Retais/patologia , Neoplasias Gástricas/patologia , Proteína Supressora de Tumor p53/análiseRESUMO
Cancer spread along the needle tract following fine needle biopsy is reported to be a rare complication. We report a case of subcutaneous implantation of hepatocellular carcinoma (HCC) following ultrasonically (US)-guided fine needle liver biopsy. The patient, a 53-year-old male was found to have a HCC at the medial segment of the liver confirmed by fine needle biopsy. Three year and four months after segmentectomy, the patient felt a subcutaneous growing lump at the previous biopsy site. The tumor was resected and confirmed histologically as HCC. We herein document other reports of such an occurrence following fine needle biopsy of HCC in Japan and consider this problem in liver biopsies.
Assuntos
Carcinoma Hepatocelular/etiologia , Neoplasias Hepáticas/etiologia , Biópsia por Agulha/efeitos adversos , Carcinoma Hepatocelular/diagnóstico , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND/AIMS: This is a comparative study of the relationship between. MATERIAL AND METHODS: Serum levels of circulating intercellular adhesion molecule-1 (cICAM-1) were measured by ELISA assay in four patients with chronic hepatitis (CH), 16 with liver cirrhosis (LC), 38 with hepatocellular carcinoma (HCC), and in nine healthy controls. RESULTS: No significant difference in cICAM-1 levels was observed between LC and HCC. The cICAM-1 level in HCC did not correlate with tumor markers but correlated well with tumor size. cICAM-1 level in HCC Stage III + IV was significantly higher than that of Stage I, and was higher in HCC with liver metastasis as opposed to HCC without metastasis. Furthermore, the cICAM-1 level of HCC decreased significantly after hepatectomy. CONCLUSION: These findings showed a close relationship between cICAM-1 and the progress of intrahepatic metastasis of HCC, indicating a possibility for using cICAM-1 as a prognostic marker.
Assuntos
Carcinoma Hepatocelular/sangue , Molécula 1 de Adesão Intercelular/sangue , Neoplasias Hepáticas/sangue , Biomarcadores Tumorais/sangue , Doença Crônica , Ensaio de Imunoadsorção Enzimática , Hepatectomia , Hepatite/sangue , Humanos , Cirrose Hepática/sangue , Metástase Neoplásica , PrognósticoRESUMO
Fas antigen (ag) is a cell surface protein known to trigger apoptosis in a variety of cells upon specific antibody binding. On the other hand, Bcl-2 protein, an oncogene product located at the mitochondrial inner surface, prolongs cell survival by blocking apoptosis. In this study we examined the expression of Fas ag and bcl-2 protein in 17 cases of hepatocellular carcinoma (HCC) to determine their role on HCC. By flow cytometric analysis, mean (SD) value of the expression of Fas ag on hepatocytes derived from normal liver, diseased liver (chronic hepatitis or liver cirrhosis) and HCC was 5.8 (4.7)%, 10.3 (6.9)%, and 24.0 (18.2)%, respectively. Fas ag expression on hepatoma cells was significantly greater than normal and diseased liver cells. The expression of Bcl-2 protein in normal liver, diseased liver and HCC was 4.3 (8.5)%, 0.8 (2.5)% and 2.1 (3.4)%, respectively, and the difference was not significant. These results suggest that induction of apoptosis may be a possible therapy against HCC.
Assuntos
Carcinoma Hepatocelular/química , Neoplasias Hepáticas/química , Proteínas Proto-Oncogênicas/análise , Receptor fas/análise , Adulto , Idoso , Apoptose , Carcinoma Hepatocelular/imunologia , Feminino , Humanos , Neoplasias Hepáticas/imunologia , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2RESUMO
To determine whether a relationship exists between DNA ploidy and the prognosis of hepatocellular carcinoma (HCC), flow cytometric DNA analysis was performed in paraffin-embedded specimens obtained from 44 patients with HCC who underwent hepatectomy. There were 26 diploid (59%) and 18 aneuploid (41%) tumors. No correlation was shown between DNA ploidy pattern and patient age, sex, liver cirrhosis, hepatitis B virus antigen and serum alpha-fetoprotein level. The ploidy pattern had no significant correlation with the presence of vascular invasion or intrahepatic metastasis. Only Edmondson's grade was well correlated with the ploidy pattern. We noted a significant correlation between survival rates and the presence of vascular invasion or intrahepatic metastasis (p < 0.05). In contrast, no significant correlation was found between DNA ploidy pattern and the prognosis of HCC. The results of this study indicate that DNA ploidy pattern may not be a useful indicator for the prognosis of HCCs after hepatic resection, unlike the results of gastric and colon cancers.
Assuntos
Carcinoma Hepatocelular/genética , DNA de Neoplasias/análise , Neoplasias Hepáticas/genética , Ploidias , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Feminino , Citometria de Fluxo , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de SobrevidaRESUMO
We report a method of endoscopic retrograde sphincterotomy in patients in whom the optimal viewing of the papilla of Vater is hardly obtained. Percutaneous transhepatic cholangiodrainage (PTCD)-tube is placed under ultrasonographic guidance. PTCD-tube coming out of the papilla of Vater is observed by the endoscope and the guide wire inside the shpincterotome is inserted into the PTCD-tube. Sphincterotome is advanced into the common bile duct by the guidance of the guide wire and PTCD-tube. Sphincterotomy is performed in a usual fashion. Two patients with previous history of gastrectomy underwent this procedure with successful results. This method should be tried when usual method of EST is difficult and unsuccessful.
Assuntos
Ampola Hepatopancreática/diagnóstico por imagem , Ductos Biliares/diagnóstico por imagem , Esfinterotomia Endoscópica/métodos , Idoso , Idoso de 80 Anos ou mais , Colangiografia , Drenagem/métodos , Cálculos Biliares/cirurgia , Gastrectomia , Humanos , Masculino , UltrassonografiaRESUMO
We experienced a patient with traumatic neuroma of the gallbladder with no history of gallbladder surgery or cholelithiasis. A 74-year-old man was referred to our department after a gallbladder tumor was incidentally discovered during a preoperative screening examination for prostate hypertrophy. Ultrasonography, MRI, CT and endoscopic retrograde cholangiography revealed a protuberant lesion of the gallbladder. Laparoscopic cholecystectomy was attempted but adhesion between the liver and duodenum forced us to convert to open laparotomy. Cholecystectomy and adjacent liver tissue resection was performed. Diagnosis was made by frozen histology during operation. It revealed no malignancy. Postoperative pathological examination revealed traumatic neuroma associated with inflammation. To our knowledge, this is the first reported case of gallbladder neuroma without a history of gallstones or surgery in the English and Japanese literature since 1980. This traumatic neuroma should be considered in a differential diagnosis in treating gallbladder neoplasm, even in the absence of an operative history or cholelithiasis.
Assuntos
Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias Pós-Traumáticas , Neuroma/diagnóstico , Idoso , Colangiografia , Colecistectomia , Colelitíase , Diagnóstico Diferencial , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Neuroma/cirurgia , Hiperplasia Prostática/cirurgiaRESUMO
A persistent problem in orthotopic liver transplantation is primary nonfunction (PNF) of the hepatic allograft. In an attempt to reduce the incidence of graft failure, the feasibility of pretransplant assessment of graft viability was investigated by 31P nuclear magnetic resonance (NMR) spectroscopy. The level of adenosine triphosphate (ATP) was measured as an indicator of liver function by 31P NMR spectroscopy after a 30 min normothermic reperfusion following cold-storage in University of Wisconsin (UW) solution. The mean +/- SD beta-ATP/Pi ratio after preservation for 0, 12, 24 or 48 h was 1.40 +/- 0.34, 0.85 +/- 0.27, 0.64 +/- 0.14 and 0.38 +/- 0.09, respectively. Significance was observed between 12h and 24h and between 12h and 48h of preservation. These results correlated well with the morphological changes in endothelial cells and sinusoidal lining cells examined by transmission electron microscopy. It is suggested strongly that microcirculatory disturbances due to endothelial cell injury impairs the recovery of ATP levels after reperfusion, and that ATP determination by 31P NMR spectroscopy, as a non-invasive modality, may help in the prediction of PNF after liver transplantation.
Assuntos
Trifosfato de Adenosina/metabolismo , Fígado/metabolismo , Soluções para Preservação de Órgãos , Preservação de Órgãos , Adenosina , Alopurinol , Animais , Glutationa , Insulina , Fígado/ultraestrutura , Espectroscopia de Ressonância Magnética , Masculino , Rafinose , Ratos , Ratos WistarRESUMO
A sustained release system for interleukin-2 (IL-2), and IL-2 mini-pellet (IL-2 mp), was developed by fusing IL-2 into a needle shaped collagen. Serum concentration of IL-2 after a single subcutaneous injection of the IL-2 mp into C57BL/6 mice remained elevated longer than after an injection of aqueous IL-2. IL-2 in the serum became undetectable by 6h after a subcutaneous injection of 1 x 10(6) unit of IL-2 in phosphate-buffered saline (PBS). In contrast, after a single subcutaneous injection of IL-2 mp containing the same amount of IL-2, the concentration of IL-2 increased to its maximum at 6h after injection, then began to decrease gradually. IL-2 was detected even on the third day after a single subcutaneous injection of one IL-2 mp. Augmentation of NK activity and generation of IL-2 activated killer cells were observed in the spleen from day 1--day 3 after a single subcutaneous injection of IL-2 mp into C57BL/6 mice. This activation was not observed following a single subcutaneous injection of the same amount of IL-2 in PBS. Adoptive immunotherapy by a single subcutaneous injection of IL-2 mp followed by intravenous injections of in vitro cultured IL-2 activated killer cells showed better results in decreasing the number of metastases of Lewis lung carcinoma in C57BL/6 mice than immunotherapy using IL-2 solution.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Implantes de Medicamento/farmacocinética , Imunoterapia Adotiva/métodos , Interleucina-2/administração & dosagem , Células Matadoras Ativadas por Linfocina/imunologia , Neoplasias Pulmonares/terapia , Animais , Preparações de Ação Retardada , Modelos Animais de Doenças , Feminino , Interleucina-2/farmacocinética , Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos C57BL , Baço/imunologiaRESUMO
The efficacy of combination chemotherapy for gastric carcinoma has been unsatisfactory, although the prognosis of advanced and recurrent disease has improved with the introduction of cisplatin (CDDP). This study examines the effect of the anti-cancer therapies CDDP, doxorubicin (ADM) and etoposide (VP-16) on the cell cycle and their cytotoxicity against two gastric carcinoma cell lines: MKN-28 (well differentiated) and MKN-45 (poorly differentiated). The treatments have different cytocidal mechanisms, and they were studied in dual combinations. For all combinations studied, cytotoxicity against MKN-45 was higher than against MKN-28. For ADM plus CDDP, or ADM plus VP-16, cytotoxicity was higher in patients pretreated with ADM than other regimens. The highest anti-tumour activity against both cell lines was obtained with ADM followed by CDDP (we have obtained good clinical results with this regimen). Schedule-dependent combined sensitivity testing of anti-cancer agents will be useful for the clinical application of therapies.
Assuntos
Antineoplásicos/farmacologia , Esquema de Medicação , Neoplasias Gástricas/patologia , Antineoplásicos/administração & dosagem , Ciclo Celular/efeitos dos fármacos , Cisplatino/administração & dosagem , Cisplatino/farmacologia , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Etoposídeo/administração & dosagem , Etoposídeo/farmacologia , Humanos , Células Tumorais CultivadasRESUMO
Recently, the treatment for hepatic metastasis has been performed by injection of chemotherapeutic agents via hepatic artery. Although this therapeutic procedure has been contributing to a relatively higher response rate, the resulting increased response has not significantly improved prognosis. So, we assessed the infusion of chemotherapeutic agents via portal vein in rabbits and compared the results with those from arterial infusion. Two weeks after inoculation of VX-2 tumor cells into the liver, subcapsularly, injection of chemotherapeutic agents as well as sampling of the livers was started. The rabbits were allocated into two groups, an arterial infusion group and a portal vein infusion group. They received a single shot of mitomycin C (MMC, 1.7 mg/kg), or 5-fluorouracil (5-FU, 9.5 mg/kg) or cisplatin (CDDP, 1.6 mg/kg) injected by infusion pump for 1 h. The drug concentration into the normal liver and intratumorally was measured by HPLC method for 5-FU and MMC, and by flameless atomic absorption spectrometry for CDDP. Either drug concentration in the liver or tumor did not substantially differ between the two groups. This experiment revealed that portal vein infusion can contribute as much drug concentration intratumorally as by arterial infusion.
Assuntos
Cisplatino/farmacocinética , Fluoruracila/farmacocinética , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Mitomicina/farmacocinética , Animais , Cisplatino/administração & dosagem , Fluoruracila/administração & dosagem , Artéria Hepática , Bombas de Infusão , Infusões Intra-Arteriais , Infusões Intravenosas , Neoplasias Hepáticas Experimentais/metabolismo , Masculino , Mitomicina/administração & dosagem , Veia Porta , CoelhosRESUMO
There have been few effective chemotherapeutic regimens for scirrhous type gastric cancer. Recently, the usefulness of combined cancer agent chemotherapy based on the concept of biochemical modulation has been reported. For example sequential MTX and 5-FU therapy, low-dose CDDP plus 5-FU, and the like. In this paper, we report the usefulness of low-dose CDDP plus 5-FU therapy in combination with pirarubicin (THP) for inoperable scirrhous type gastric cancer. A 32-year-old man who was suffering from scirrhous type gastric cancer with pyloric stenosis was treated with this regimen. Eight weeks after the start of therapy, his gastric capacity and lumen diameter had clearly increased, and he was taking ordinary meals. Ascites had also completely disappeared. CR has now been continued about 7 months. This regimen is considered to be promising for scirrhous type gastric cancers with a poor prognosis.
Assuntos
Adenocarcinoma Esquirroso/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Esquema de Medicação , Fluoruracila/administração & dosagem , Humanos , Infusões Intravenosas , MasculinoRESUMO
In order to evaluate the immune response in cancer patients treated with adjuvant immunochemotherapy, a committee was organized in Japanese research Society for Surgical Cancer Immunology. Skin reactions, subsets of PBL, HLA, immunosuppressor (IAP), Immunoactivity (NK activity and lymphoblastogenesis with PHA), general nutritional condition and performance status were picked up and discussed as to how these reactions influence the prognosis of patients. For example, 395 cases of gastric cancer (excluded stage I, non-chemotherapy and absolute non-curative resection) collected from the committee's hospital were divided into two groups, according to a statistical "cut off point", i.e., more than 5.9g/dl of TP, 4.0g/dl of Alb, and 1500/mm3 of PBL, and values less than these. The five-year survival rate was significantly high in the former group. In the group that kept high counts of these parameters after operation, the 5-year survival rate was significantly high in cases which received immunotherapy. In conclusion, immunoparameters paralleled to the stage of disease and prognosis. When the parameters remained at high levels after operation, the immunotherapy group showed good survival compared to the non-immunotherapy group. Immunotherapy is not valuable in patients with high IAP levels and poor nutritional condition.
Assuntos
Fatores Imunológicos/uso terapêutico , Neoplasias/terapia , Humanos , Neoplasias/imunologia , Neoplasias Gástricas/imunologiaRESUMO
Many BRMs (biological response modifiers) have been used for post-operative immunochemotherapy. And their usefulness were also reported. Nevertheless it is still unknown that which route, how much doses and which timing are the most effective to administer these drugs. We used BRMs intratumorally and preoperatively. To reconfirm the efficacy of intratumoral injection therapy randomized study was performed in gastric carcinoma. Three hundred and ninety-five cases were entered, 199 cases in group A which were treated preoperatively with OK-432 intratumorally and 196 cases in group B which were control, respectively. In the cases which had marked infiltration of lymphoid cells in tumor sites, the two year survival rate of group A was significantly better than that of group B (p less than 0.05). On the study of recurrent forms, the distal lymph node metastasis was markedly decreased in group A. The ratio of metastasis to the distal lymph nodes in group A was 5-10% lesser than that in group B on the each depth of tumor invasion. The ratio of lymph nodes metastasis was almost similar in the each group, but the number of metastatic lymph nodes was significantly reduced in high grade tumor infiltrated cases in group A (p less than 0.005). These results suggest that preoperative endoscopically intratumoral administration of OK-432 suppresses the lymph node metastasis and improves the postoperative survival rate.
Assuntos
Produtos Biológicos/administração & dosagem , Picibanil/administração & dosagem , Neoplasias Gástricas/terapia , Terapia Combinada , Gastroscopia , Humanos , Metástase Linfática , Neoplasias Gástricas/mortalidade , Taxa de SobrevidaAssuntos
Úlcera Duodenal/patologia , Úlcera Gástrica/patologia , Adulto , Envelhecimento , Animais , Gatos , Feminino , Humanos , MasculinoAssuntos
Adenocarcinoma/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dano ao DNA , Neoplasias Retais/genética , Neoplasias Gástricas/genética , Proteína Supressora de Tumor p53/análise , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Adulto , Idoso , Apoptose , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Proteína Supressora de Tumor p53/genéticaRESUMO
A case of surgically confirmed primary malignant fibrous histiocytoma of the liver is presented. A 35-year-old man was admitted to hospital with an epigastric mass. No abnormal laboratory findings, including tumor markers, were detected. Ultrasound and computed tomography showed the main tumor in the left lateral segment and a daughter nodule in the posterior segment of the liver. Arteriography demonstrated a slightly hypervascular mass in the left lateral segment. Histological examination of the resected tumor showed bundles of spindle cells with a focal storiform pattern, which were intermingled with bizarre giant cells, therefore a diagnosis of malignant fibrous histiocytoma was made.
Assuntos
Histiocitoma Fibroso Benigno/patologia , Neoplasias Hepáticas/patologia , Adulto , Biomarcadores Tumorais/análise , Hepatectomia , Histiocitoma Fibroso Benigno/cirurgia , Humanos , Técnicas Imunoenzimáticas , Fígado/patologia , Testes de Função Hepática , Neoplasias Hepáticas/cirurgia , Masculino , Microscopia EletrônicaRESUMO
To investigate, by a multi-institutional randomized trial, the prognostic significance of the augmentation of tumour-infiltrating lymphocytes (TILs) by preoperative intratumoral injection of OK-432 (OK-432 it), a bacterial biological response modifier, in patients with gastric cancer. The 10-year survival and disease-free survival were examined and analysis of the factors showing survival benefit was performed. 370 patients who had undergone curative resection of gastric cancer were enrolled in this study and followed up for 10 years postoperatively. Patients were randomized into either an OK-432 it group or a control group. Ten Klinishe Einheit (KE) of OK-432 was endoscopically injected at 1 to 2 weeks before the operation in the OK-432 it group. Both groups received the same adjuvant chemoimmunotherapy consisting of a bolus injection of mitomycin C (0.4 mg kg(-1) i.v.) and administration of tegafur and OK-432 from postoperative day 14 up to 1 year later. Tegafur (600 mg day(-1)) was given orally and OK-432 (5 KE/2 weeks) was injected intradermally for a maintenance therapy. The TILs grades in resected tumour specimens and presence of metastasis and metastatic pattern in dissected lymph nodes were examined. Multivariate analysis was performed to determine the efficacy of OK-432 it on prognostic factors. All patients were followed up for 10 years. The overall 5- and 10-year survival rates and disease-free survival rates of the OK-432 it group were not significantly higher than those of the control group. However, OK-432 it significantly increased the 5- and 10-year survival rates of patients with stage IIIA + IIIB, moderate lymph node metastasis (pN2), and positive TILs. OK-432 it was most effective at prolonging the survival of patients who had both positive TILs and lymph node metastasis. The OK-432 it group with positive TILs showed a significant decrease in metastatic lymph node frequency and in the number of lymph node micro- metastatic foci when compared to the control group. This study showed that only one time preoperative OK-432 it, particularly when it triggers TILs, is effective for reduction of regional lymph node metastasis. OK-432 it probably acts partly by eliminating micro-metastatic foci in lymph nodes. Preoperative intratumoral injection of OK-432 is technically very easy and has no serious adverse effects, so it is a promising form of neoadjuvant immunotherapy for advanced gastric cancer.