RESUMO
This paper describes a new surgical technique and our clinical experience with video-assisted endoscopic total glandectomy via a middle axillary incision followed by immediate reconstruction with latissimus dorsi muscle flap (LDMF) performed in 17 patients with bigger, multiple tumors or extensive ductal spread of breast cancer. The novel techniques in this procedure are as follows: (1) By securing patients in a semi-lateral position and suspending the upper extremity, either supine or semi-lateral position can be easily achieved by simply rotating the operating table, resulting in a wider working space from the axillary to hip area. (2) By applying a retractor for skin flap traction, endoscopic glandectomy and reconstruction become safe and reliable. As a result, the mean number and size of tumors were 1.2 and 4.12 cm, respectively. Surgical margins of all the cases were pathologically negative and there were no recurrences observed during 14 months follow-up to date. Esthetic results have been satisfactory and the surgical wounds were not visible from the front in any case. Compared to mastectomy, this procedure shows the same therapeutic results, but offers a greater esthetic and psychological advantage to all the patients.
Assuntos
Neoplasias da Mama/cirurgia , Excisão de Linfonodo/métodos , Mamoplastia/métodos , Cirurgia Vídeoassistida/métodos , Neoplasias da Mama/patologia , Endoscopia/métodos , Endoscopia/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Excisão de Linfonodo/instrumentação , Excisão de Linfonodo/estatística & dados numéricos , Mamoplastia/instrumentação , Mamoplastia/estatística & dados numéricos , Pessoa de Meia-Idade , Cirurgia Vídeoassistida/instrumentação , Cirurgia Vídeoassistida/estatística & dados numéricosRESUMO
Breast conservation surgery has become a standard operation as a minimally invasive surgery for breast cancer in Japan. Now sentinel lymph node biopsy (SLNB), day surgery, and endoscopy assisted surgery are being introduced as more minimally invasive surgeries for breast cancer. When blue dye and/or isotope are injected into the peri-tumoral breast gland, the sentinel lymph nodes (SLN) can be detected easily, and node negative patients can be selected with certainty. When no metastasis is found in SLN by frozen section, T1N0 breast cancer patients can be treated without lymph node dissection. Using this technique, day surgery for patients who have clinically node-negative small breast cancer (less than 1.5 cm in diameter) is performed under local anesthesia. We have developed an endoscopy assisted conservation surgery for breast cancer. Using endoscopy, partial or total glandectomy with radical axillary lymph node dissection is performed via a 5 cm skin incision on the middle axillary line. When the amount of glandectomy is over one third, we perform immediate reconstruction using the latissimus dorsi. These minimally invasive surgeries for breast cancer will result in a better quality of life for breast cancer patients.
Assuntos
Neoplasias da Mama/cirurgia , Mastectomia Segmentar/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Adulto , Idoso , Procedimentos Cirúrgicos Ambulatórios , Neoplasias da Mama/patologia , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Pessoa de Meia-Idade , Biópsia de Linfonodo Sentinela/métodosRESUMO
To determine the possible contribution of apoptosis in the pathogenesis of acute lung injury (ALI), we investigated Fas antigen (Fas), Fas ligand (FasL), perforin, granzyme A, and granzyme B expressions in a murine model of ALI after intratracheal instillation of Escherichia coli lipopolysaccharide (LPS: 0.3-30 microg) into the left lung. Lung injury, examined by water-to-dry weight ratio and albumin leakage, demonstrated maximal epithelial injury 1 d after 30 microg LPS instillation. Expressions of the proapoptosis molecules' mRNA were dose-dependently up-regulated, with maximal expression in the early phase in the instilled lung and most apparent 1 d after LPS instillation. Negligible mRNA expression of proapoptosis molecules was observed in noninstilled lungs. The terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL) demonstrated positive signals in neutrophils and macrophages as well as in alveolar wall cells of the instilled lung 1 d after LPS instillation. Immunohistochemistry demonstrated that Fas was up-regulated in alveolar and inflammatory cells and FasL-positive inflammatory cells migrated into the air spaces in the LPS-instilled lung. Intratracheal administration of P2 antibody, which is an anti-Fas blocking antibody, attenuated the lung injury after 30 microg LPS instillation without attenuating mRNA expressions of proapoptosis molecules and neutrophil accumulation in the lung. In contrast, concanamycin A, which inhibits the function of perforin, did not alter the outcome after LPS instillation. These results indicate that the Fas/FasL system could be important in the pathogenesis of LPS-induced ALI, and proper regulation of the FasL/Fas system might be important for potential treatment of ARDS.
Assuntos
Antígenos de Superfície/fisiologia , Apoptose , Imunoglobulinas/fisiologia , Glicoproteínas de Membrana/fisiologia , Neuropeptídeos/fisiologia , Alvéolos Pulmonares/patologia , Receptores do Fator de Necrose Tumoral , Síndrome do Desconforto Respiratório/patologia , Animais , Proteína Ligante Fas , Lipopolissacarídeos/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos ICR , Síndrome do Desconforto Respiratório/induzido quimicamente , Receptor fasRESUMO
E2F is a family of transcription factors which regulates cell cycle and apoptosis of mammalian cells. E2F-1-3 localize in the nucleus, and preferentially bind pRb, while E2F-4 and 5 have no nuclear localization signal and preferentially bind p107/p130. E2F-6 suppresses the transcriptional activity of other E2F proteins. DP-1 and 2 are heterodimeric partners of each E2F protein. Using tetracycline-responsive promoters, here we compared the effects of ectopic expression of E2F-1, DP-1 and E2F-4 on cell cycle progression and apoptosis in Chinese hamster cell lines. We found that E2F-4, as well as DP-1 and E2F-1, induced growth arrest and caspase-dependent apoptosis. E2F-4 did not have a marked effect on cell cycle progression, while E2F-1 induced DNA synthesis of resting cells and DP-1 arrested cells in G1. Ectopic expression of E2F-4 did not activate E2F-dependent transcription. Our results suggest that expression of E2F-4 at elevated levels induces growth arrest and apoptosis of mammalian cells through a mechanism distinct from E2F-1 and DP-1.
Assuntos
Apoptose/fisiologia , Proteínas de Transporte , Caspases/fisiologia , Proteínas de Ciclo Celular , Proteínas de Ligação a DNA/fisiologia , Fatores de Transcrição/fisiologia , Animais , Células CHO , Ciclo Celular/fisiologia , Cricetinae , Cricetulus , Replicação do DNA/fisiologia , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/genética , Fatores de Transcrição E2F , Fator de Transcrição E2F1 , Fator de Transcrição E2F4 , Fator de Transcrição E2F6 , Regulação da Expressão Gênica/efeitos dos fármacos , Regiões Promotoras Genéticas , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/fisiologia , Proteína 1 de Ligação ao Retinoblastoma , Tetraciclina/farmacologia , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Ativação Transcricional , TransfecçãoAssuntos
Citotoxicidade Celular Dependente de Anticorpos , Caspases/metabolismo , Serina Endopeptidases/metabolismo , Transplante Heterólogo/imunologia , Animais , Citotoxicidade Celular Dependente de Anticorpos/efeitos dos fármacos , Linhagem Celular , Granzimas , Humanos , Rim , Inibidores de Serina Proteinase/farmacologia , SuínosAssuntos
Citotoxicidade Celular Dependente de Anticorpos , Apoptose/imunologia , Genes bcl-2 , Glicoproteínas de Membrana/imunologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Serina Endopeptidases/metabolismo , Receptor fas/imunologia , Animais , Anticorpos Heterófilos/imunologia , Linhagem Celular , Proteína Ligante Fas , Humanos , Rim , Camundongos , Perforina , Proteínas Citotóxicas Formadoras de Poros , Suínos , Linfócitos T Citotóxicos/imunologia , TransfecçãoRESUMO
A bacterium, strain NM 5-3, isolated from soil exhibited the highest cyclo(Gly-Leu) (CGL)-hydrolyzing activity and was identified as Agrobacterium radiobacter. The reaction products from CGL were dipeptides (Leu-Gly and Gly-Leu) and amino acids (Leu and Gly). Inhibitors for the dipeptidase of this strain did not inhibit the hydrolysis of CGL to dipeptides, indicating that two distinct enzymes, CGLase and a dipeptidase, were involved in its hydrolysis. The activities of these two enzymes were separated by anion-exchange column chromatography. The results indicated that strain NM5-3 hydrolyzed CGL via the dipeptides to the corresponding amino acids. The CGLase fraction was found to catalyze the hydrolysis of cyclo(Gly-D-Leu), cyclo(Gly-Gly), cyclo(L-Ala-Gly), and cyclo(D-Ala-Gly). On the other hand, the dipeptidase fraction exhibited L-specific substrate specificity.
Assuntos
Citotoxicidade Celular Dependente de Anticorpos , Glicoproteínas de Membrana/imunologia , Transplante Heterólogo/imunologia , Animais , Células Cultivadas , Proteína Ligante Fas , Regulação da Expressão Gênica/imunologia , Humanos , Interleucina-2/farmacologia , Células Matadoras Ativadas por Linfocina/imunologia , Glicoproteínas de Membrana/genética , Metaloendopeptidases/antagonistas & inibidores , Inibidores de Proteases/farmacologia , Proteínas Recombinantes/imunologia , Suínos , TransfecçãoAssuntos
Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Coração/imunologia , Imunossupressores/uso terapêutico , Propilenoglicóis/uso terapêutico , Transplante Heterólogo/imunologia , Animais , Anticorpos Heterófilos/sangue , Terapia Combinada , Cricetinae , Cloridrato de Fingolimode , Sobrevivência de Enxerto/imunologia , Guanidinas/uso terapêutico , Transplante de Coração/patologia , Terapia de Imunossupressão/métodos , Teste de Cultura Mista de Linfócitos , Ratos , Ratos Endogâmicos Lew , Esfingosina/análogos & derivados , Baço/imunologia , Esplenectomia , Transplante Heterólogo/patologiaAssuntos
Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Transplante de Rim , Doadores Vivos , Adulto , Feminino , Hepacivirus/isolamento & purificação , Hepatite C/transmissão , Humanos , Transplante de Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Viral/genética , RNA Viral/isolamento & purificaçãoAssuntos
Hiperinsulinismo/prevenção & controle , Transplante de Pâncreas , Tiazolidinedionas , Animais , Cromanos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Masculino , Sistema Porta/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Ratos , Ratos Endogâmicos Lew , Tiazóis/uso terapêutico , TroglitazonaRESUMO
In order to clarify the role of natural killer (NK) cells in delayed xenograft rejection (DXR) of discordant xenotransplantation, we used in vitro xenogeneic combination of human NK cells and pig kidney target cells (PK15), and investigated the mechanism of xenogeneic cytotoxicity caused by human NK cells. In the presence of decomplemented human serum or human IgG, freshly isolated human peripheral blood lymphocytes (PBLs) caused both membrane (51Cr release) and DNA (3H release) damage on PK15. In contrast, only membrane damage was detected in the presence of normal human serum. To clarify the participation of perforin/granzymescell mediated cytotoxicity (P/G-CMC), when EGTA or concanamycin B (CMB) was added to the cytotoxicity assays, both cytotoxicities were completely inhibited by these drugs in a dose-dependent manner. In terms of the involvement of Fas/FasL-based cytotoxicity (F-CMC), while the cytotoxicity assays were performed in the presence of antagonistic anti-human FasL mAb, this antibody was not able to block the cytotoxicity. From these results, it is concluded that xenogeneic cytotoxicity is due to NK cell dependent ADCC (antibody-dependent cell-mediated cytotoxicity), and their effector mechanism can cause apoptosis on target cells via P/G-CMC.
Assuntos
Apoptose/imunologia , Citotoxicidade Imunológica , Transplante Heterólogo/efeitos adversos , Transplante Heterólogo/imunologia , Animais , Citotoxicidade Celular Dependente de Anticorpos , Linhagem Celular , Proteína Ligante Fas , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/imunologia , Humanos , Técnicas In Vitro , Células Matadoras Naturais/imunologia , Glicoproteínas de Membrana/metabolismo , Perforina , Proteínas Citotóxicas Formadoras de Poros , Suínos , Receptor fas/metabolismoAssuntos
Sobrevivência de Enxerto/fisiologia , Transplante de Coração/fisiologia , Imunossupressores/uso terapêutico , Glicoproteínas de Membrana/genética , Propilenoglicóis/uso terapêutico , Serina Endopeptidases/genética , Transcrição Gênica/efeitos dos fármacos , Animais , Primers do DNA , Cloridrato de Fingolimode , Sobrevivência de Enxerto/efeitos dos fármacos , Granzimas , Transplante de Coração/imunologia , Imunossupressores/farmacologia , Perforina , Reação em Cadeia da Polimerase , Proteínas Citotóxicas Formadoras de Poros , Propilenoglicóis/farmacologia , RNA Mensageiro/genética , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Esfingosina/análogos & derivados , Linfócitos T Citotóxicos/imunologia , Transplante HomólogoAssuntos
Apoptose/fisiologia , Caspases , Cisteína Endopeptidases/metabolismo , Imunossupressores/farmacologia , Linfoma/imunologia , Propilenoglicóis/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caspase 1 , Caspase 2 , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/patologia , Relação Dose-Resposta a Droga , Ativação Enzimática , Cloridrato de Fingolimode , Cinética , Linfoma/enzimologia , Linfoma/patologia , Camundongos , Proteínas/metabolismo , Esfingosina/análogos & derivados , Células Tumorais CultivadasAssuntos
Citotoxicidade Celular Dependente de Anticorpos , Linfócitos/imunologia , Glicoproteínas de Membrana/fisiologia , Transplante Heterólogo/imunologia , Receptor fas/fisiologia , Animais , Antígenos Heterófilos/imunologia , Apoptose , Células Clonais , Dano ao DNA , Proteína Ligante Fas , Humanos , Glicoproteínas de Membrana/genética , Camundongos , Proteínas Recombinantes/biossíntese , Suínos , Transfecção , Receptor fas/genéticaRESUMO
A 64-year-old female who was diagnosed with an amylase-producing tumor of unknown origin was treated by hyperthermochemotherapy. The patient was admitted with a complaint of abdominal fullness due to ascites. Laboratory examination showed high levels of serum amylase and tumor markers, including CA15-3, CA 125 and CA 72-4. Laparotomy showed peritoneal dissemination with histological findings of adenocarcinoma of unknown origin. After laparotomy, she was given hyperthermia combined with chemotherapy using carboplatin (CBDCA), mitomycin C (MMC) and doxifluridine (5'-DFUR). Hyperthermia (13.56 MHz radiofrequency for 40-50 min) was performed a total of six times within one and a half months. The total doses of CBDCA and MMC were 450 mg and 24 mg, respectively, and 600 mg of 5'-DFUR was orally administered every day. By these combined treatments, ascites disappeared and serum levels of amylase and all tumor markers were decreased and normalized. MRI and echo examination also showed complete disappearance of peritoneal metastasis. Two and a half years after the treatment, the patient is alive without any evidence of recurrence, which suggests that this combined therapy is one of the useful modalities for peritoneal dissemination as well as an inoperable tumor itself.