RESUMO
Activation of the angiogenic process occurs during tumorigenesis, as does disturbance of cell proliferation and apoptosis. Seeking a potential correlation, we investigated tumor cell apoptosis, proliferation, and angiogenesis in the adenoma-carcinoma sequence of colorectal carcinogenesis using an in situ apoptosis detection kit and MIB-1 and anti-CD34 antibodies in 27 adenomas with low dysplasia, 17 adenomas with high dysplasia, and 26 carcinomas in adenoma, as well as assessed p53 and bcl-2 expressions. The results showed that the potential for apoptosis was augmented, paralleling the increment of proliferation, in adenomas with low dysplasia but diminished when adenomas progressed from low dysplasia to high dysplasia and cancer. A gradual increment of microvessel density was observed during the progression with an increase during transition from low dysplasia to high dysplasia and cancer. Correlation coefficient test showed an inverse correlation between apoptotic index and microvessel density when all of the lesions were taken into account. No apparent impact of aberrant p53 on angiogenesis or bcl-2 on apoptosis was observed in this study. These results suggest that the angiogenesis initiates during transition from low dysplasia to high dysplasia and cancer, which may, in turn, contribute to the reduction of tumor cell apoptosis during colorectal carcinogenesis.
Assuntos
Apoptose , Neoplasias Colorretais/irrigação sanguínea , Neoplasias Colorretais/patologia , Neovascularização Patológica/patologia , Adenocarcinoma/irrigação sanguínea , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenoma/irrigação sanguínea , Adenoma/metabolismo , Adenoma/patologia , Idoso , Divisão Celular/genética , Neoplasias Colorretais/metabolismo , Feminino , Humanos , Mucosa Intestinal/irrigação sanguínea , Mucosa Intestinal/patologia , Intestino Grosso/irrigação sanguínea , Intestino Grosso/patologia , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteína Supressora de Tumor p53/biossínteseRESUMO
To investigate the relationship between tumor angiogenesis and the expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/dThdPase) and between patients' survival and the expression of PD-ECGF/ dThdPase in human gastric carcinoma tissues, we performed immunohistochemical studies with anti-PD-ECGF/dThdPase and anti-CD34 monoclonal antibodies. Out of 154 gastric carcinoma tissue samples, 61 (40%) were evaluated as PD-ECGF/ dThdPase-positive. The expression of PD-ECGF/dThdPase was significantly associated with the intratumoral microvessel counts (P < 0.0001) and the incidence of hematogenous metastasis (P < 0.05). Intratumoral vessel counts were significantly correlated with overall survival of 154 patients (P < 0.000001). Cox proportional hazards model showed that tumor vasculature was an independent and strong prognostic variable. However, the prevalence of the expression of PD-ECGF did not associate the overall survival. We suggest that expression of PD-ECGF/dThdPase plays a role in the promotion of angiogenesis in human gastric carcinomas, without any definite influence on patient's survival.
Assuntos
Adenocarcinoma/enzimologia , Neovascularização Patológica/fisiopatologia , Fator de Crescimento Derivado de Plaquetas/metabolismo , Neoplasias Gástricas/enzimologia , Timidina Fosforilase/metabolismo , Adenocarcinoma/irrigação sanguínea , Idoso , Western Blotting , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/irrigação sanguínea , Análise de SobrevidaRESUMO
It is occasionally difficult to differentiate between multiple primary and metastatic tumors in case of multiple carcinomas. p53 gene mutation pattern by PCR-SSCP and a clonality analysis on the human androgen receptor gene (HUMARA) in multiple tumors were used to distinguish whether carcinomas were multiple primary tumors or a metastasis. Three female patients with multiple carcinomas, who had undergone surgical resection, were selected for these analyses as typical candidates from 11 cases tested. In the first case with bilateral breast cancer the combined analyses were performed on DNA extracted from tumor portions in paraffin sections of each tumor sample and the results indicated that the carcinomas consisted of a primary carcinoma and metastatic tumors. The carcinomas in the second patient consisted of multiple primary carcinomas and the tumors in the third patient consisted of two independent primary carcinomas with different clonal origins. Thus a combination of p53 gene mutation analysis and clonality analysis on HUMARA provided useful, reliable evidence which can help in discriminating multiple primary tumors from metastatic tumors.
Assuntos
Genes p53/genética , Metástase Neoplásica/genética , Neoplasias Primárias Múltiplas/genética , Receptores Androgênicos/genética , Idoso , Células Clonais , Análise Mutacional de DNA , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Metástase Neoplásica/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Proteína Supressora de Tumor p53/análiseRESUMO
Although small cell carcinoma of the gallbladder is rare, the prognosis of this tumor type is poorer than that of differentiated carcinomas. We report herein the case of a 62-year-old man with small cell carcinoma of the gallbladder. The operative findings showed an unresectable large tumor of the gallbladder and multiple metastases involving the liver and lymph nodes. Pathological findings revealed small sized carcinoma cells, round or oval in shape which displayed a cord-like or solid appearance. Diagnosis was confirmed by ultrastructural study that showed the presence of neurosecretory-type cored granules. He was treated by intraarterial chemotherapy with cisplatin and etoposide. Six months later, abdominal computed tomography scan confirmed loss of the large mass. A complete response to the chemotherapy was noted over a period of six months, suggesting the efficacy of intraarterial chemotherapy for this disease. Fifty-three cases of small cell carcinoma reported in the English literature are reviewed. In most cases, including ours, a radical operation was not indicated and the prognosis was extremely poor, due to the difficulty of early diagnosis and the rapid progression of the disease. Chemotherapy is effective in general and intraarterial chemotherapy performed in the present case may be particularly useful to improve survival.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Pequenas/tratamento farmacológico , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Neoplasias da Vesícula Biliar/tratamento farmacológico , Infusões Intra-Arteriais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Carcinoma de Células Pequenas/patologia , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/secundário , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , RadiografiaRESUMO
Mesenteric cysts are rare intra-abdominal lesions. We present a case of a mesenteric cyst that was discovered by abdominal computed tomography (CT) and excised by retroperitoneoscopic surgery. There have been 10 reports of excision of mesenteric cysts by laparoscopy in the literature, but retroperitoneoscopic resection of such cysts has not been reported. This case suggests that when a mesenteric cyst arises from the ascending or descending colon, the retroperitoneal approach has a lower risk of traumatizing the bowel than does the laparoscopic intra-abdominal approach, and it does not have to compress other intra-abdominal organs.
Assuntos
Laparoscopia/métodos , Cisto Mesentérico/cirurgia , Adulto , Colo/cirurgia , Feminino , Humanos , Espaço RetroperitonealRESUMO
In 173 patients with operable gastric cancer and in 127 patients with colorectal cancer, the relations between thymidine uptake by cancer cells in semi-solid media, their clinico-pathologic features and survival times, were studied. Multivariate analysis using Cox proportional hazard model showed that thymidine uptake is one of the variables most highly correlated with the probability of patient death. Thus, the availability of thymidine uptake information in the perioperative period may be useful for selecting patients who would benefit from more intensive therapy. Thymidine kinase (TK) is the only enzyme by which thymidine is introduced into the DNA metabolism. In 64 specimens, including gastric and colorectal cancers, TK levels in the serum and tumors were measured accordingly. However, there was no correlation between thymidine uptake and the TK levels, suggesting the necessity of measuring thymidine phosphorylase activity as well.
Assuntos
Neoplasias do Colo/mortalidade , Neoplasias Gástricas/mortalidade , Timidina , Idoso , Neoplasias do Colo/enzimologia , Neoplasias do Colo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Timidina/farmacocinética , Timidina Quinase/metabolismo , Timidina Fosforilase/metabolismo , Células Tumorais CultivadasRESUMO
A 68-year-old female underwent radical mastectomy for left breast cancer in April, 1995. She was treated with conventional combination chemotherapy (CEF) before and after surgery as an adjuvant therapy. She was treated with oral tamoxifen (TAM) and/or medroxyprogesterone (MPA) and doxifluridine daily after surgery. In May, 1998, she was found to have developed a subcutaneous tumor of the head and skull-bone, and a meningeal metastasis. We treated her with 80 mg docetaxel (TXT) one time with radiation (total dose 50 Gy), and with 70 mg two times. After the combination therapy, she achieved partial remissions of the metastases and a decrease in serum CEA. Adverse reactions to TXT were grade 3 alopecia, grade 3 to 4 neutropenia, grade 2 to 3 stomatitis, and grade 2 diarrhea. All were tolerable and reversible. The combination therapy of radiation and TXT may be a good strategy for recurrent breast cancer.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias da Mama/patologia , Paclitaxel/análogos & derivados , Radiossensibilizantes/administração & dosagem , Neoplasias Cutâneas/secundário , Neoplasias Cranianas/secundário , Taxoides , Idoso , Neoplasias da Mama/cirurgia , Terapia Combinada , Docetaxel , Feminino , Humanos , Mastectomia Radical , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/secundário , Paclitaxel/administração & dosagem , Dosagem Radioterapêutica , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/radioterapia , Neoplasias Cranianas/tratamento farmacológico , Neoplasias Cranianas/radioterapiaRESUMO
Drug resistance in chemotherapy is a significant problem in the treatment of gastric carcinomas as well as other malignant tumors. Multidrug resistant cells frequently overexpress the 170 kDa P-glycoprotein (P-gp). Twenty-four fresh tumor specimens of gastric carcinoma were assessed by flow cytometric detection of P-gp using monoclonal antibody C219. Eight patients were P-gp positive. Differentiated gastric carcinomas contained significantly higher concentrations of P-gp positive. Incidence of P-gp positive case was high in advanced stage. Sixteen cases received in vitro chemosensitivity test assessed by thymidine incorporation assay (TIA). Seven of 9 multidrug resistant cases by TIA were P-gp positive, and all of 7 non-multidrug resistance were negative. Expression of P-gp and multidrug resistance were closely correlated (p < 0.01). Also, in 89 patients with operable gastric carcinoma, the relationship between multidrug resistance by TIA and their clinicopathologic features as well as their survival lengths were examined. Thirty-one of 89 specimens from gastric carcinoma patients were multidrug resistant by TIA. Patients with multidrug resistant group had a significantly poorer cumulative survival rate than non-multidrug resistant cases (p < 0.01). The multivariated analyses showed that multidrug resistance analyzed is useful indicator for prognosis (p < 0.1). We suggest that multidrug resistance cases or P-gp-positive cases of gastric carcinoma are highly malignant, and these determinations are clinically useful.