RESUMO
Numerical simulation and experimental investigation of laser-MIG hybrid angle-welding low-carbon 1.5-mm-thin SPCC steel sheets are presented in this work. The transient simulation analysis provides an access to the thermal-fluid phenomena prediction by employing a hybrid three-dimensional heat source model. Special attention is paid to the melt dynamic behaviors within the triangular molten pool affected by the Marangoni convection. The simulation results show that the temperature and its gradient distribution are symmetrical with respect to the laser beam, which is validated well by the experimental study. The microstructure of the welded joints was analyzed by scanning electron microscopy and transmission electron microscopy. The results show that the cross-section microstructures of welded joint are mainly composed of the weld zone, narrow heat-affected zone, and substrate. The semielliptic-like molten pool shape is consistent with that of the simulated results. The finer microstructure in the weld bead results from the rapid cooling rate of laser welding confirmed by the FEM calculation. The columnar and equiaxed dendrites are formed in the peripheral and central region of the molten pool, which is beneficial for the improvement of the microhardness.
RESUMO
AIMS: This study aimed to strengthen the reducing equivalent generation in Klebsiella pneumoniae for improving 1,3-propanediol (PDO) production. METHODS AND RESULTS: Disruption of the arcA gene activated the transcription levels of the TCA cycle genes and thus increased the NADH/NAD+ ratio by 54·2%, leading to the improved PDO titre and yield per cell from 16·1 g l-1 and 4·0 g gDCW-1 to 18·8 g l-1 and 6·4 g gDCW-1 respectively. Further ldhA gene deletion eliminated lactate accumulation and promoted the PDO titre to 19·9 g l-1 . Finally, the glucose effect was weakened by deleting the crr gene to enhance the co-utilization of glucose and glycerol, resulting in the increased PDO production to 23·8 g l-1 with the glycerol conversion rate of 59·5%. The PDO titre in bioreactor was promoted from 61·2 to 78·1 g l-1 . CONCLUSIONS: Deletions of the arcA and the crr genes showed positive effects on the TCA cycle activity and the co-utilization of glucose and glycerol, leading to the strengthened reducing equivalent generation and the improved PDO titre by 47·8% in shaker. The PDO titre in the bioreactor was enhanced to 78·1 g l-1 . SIGNIFICANCE AND IMPACT OF THE STUDY: This study provided novel information on generating reducing equivalent for the PDO biosynthesis by strengthening the TCA cycle and weakening the glucose effect in K. pneumoniae.
Assuntos
Proteínas de Bactérias/genética , Ciclo do Ácido Cítrico , Glucose/metabolismo , Klebsiella pneumoniae/genética , Propilenoglicóis/metabolismo , Proteínas de Bactérias/metabolismo , Reatores Biológicos , Glicerol/metabolismo , Klebsiella pneumoniae/metabolismo , Ácido Láctico/metabolismoRESUMO
As we learn more about the etiology and cancer risks associated with Lynch syndrome (LS), the phenotypic spectrum of this condition and its genotype-phenotype correlations are being elucidated. We report a patient with past history of multiple cancers including colon and kidney cancer, and recently diagnosed with jejunal adenocarcinoma. The patient had microsatellite instability and immunohistochemistry (MSI/IHC) testing performed on his small bowel cancer in order to evaluate his risk for LS. The MSI/IHC results on his tumor tissue were reported as abnormal and subsequent blood draw revealed the presence of a germline MSH6 mismatch repair gene mutation. This case highlights the phenotypic variability of LS and complications it may present in evaluation for diagnosis and appropriate surveillance and management recommendations. To our knowledge, this is the first report of MSI/IHC being done on small bowel cancer to evaluate for this condition and subsequently confirmed via molecular analysis.
Assuntos
Adenocarcinoma/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias do Jejuno/genética , Adenocarcinoma/patologia , Idoso , Carcinoma de Células Renais/patologia , Proteínas de Ligação a DNA/genética , Mutação em Linhagem Germinativa , Humanos , Imuno-Histoquímica , Neoplasias do Jejuno/patologia , Neoplasias Renais/patologia , Masculino , Instabilidade de Microssatélites , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/genética , LinhagemRESUMO
Apicomplexan parasites of the genus Eimeria are the major causative agent of avian coccidiosis, leading to high economic losses in the poultry industry. Recent results show that Eimeria tenella harbours an apicoplast organelle, and that a key biosynthetic enzyme, enoyl reductase, is located in this organelle. In related parasites, enoyl reductase is one component of a type II fatty acid synthase (FAS) and has proven to be an attractive target for antimicrobial compounds. We cloned and expressed the mature form of E. tenella enoyl reductase (EtENR) for biochemical and structural studies. Recombinant EtENR exhibits NADH-dependent enoyl reductase activity and is inhibited by triclosan with an IC50 value of 60 nm. The crystal structure of EtENR reveals overall similarity with other ENR enzymes; however, the active site of EtENR is unoccupied, a state rarely observed in other ENR structures. Furthermore, the position of the central beta-sheet appears to block NADH binding and would require significant movement to allow NADH binding, a feature not previously seen in the ENR family. We analysed the E. tenella genomic database for orthologues of well-characterized bacterial and apicomplexan FAS enzymes and identified 6 additional genes, suggesting that E. tenella contains a type II FAS capable of synthesizing saturated, but not unsaturated, fatty acids. Interestingly, we also identified sequences that appear to encode multifunctional type I FAS enzymes, a feature also observed in Toxoplasma gondii, highlighting the similarity between these apicomplexan parasites.
Assuntos
Eimeria tenella/enzimologia , Ácidos Graxos Dessaturases/química , Ácidos Graxos Dessaturases/metabolismo , Ácido Graxo Sintase Tipo II/química , Ácido Graxo Sintase Tipo II/metabolismo , Ácido Graxo Sintase Tipo I/metabolismo , Ácidos Graxos/biossíntese , Sequência de Aminoácidos , Animais , Sítios de Ligação , Eimeria tenella/genética , Eimeria tenella/metabolismo , Ácidos Graxos Dessaturases/genética , Modelos Moleculares , Dados de Sequência Molecular , Conformação Proteica , Proteínas RecombinantesRESUMO
Apicomplexan parasites, Eimeria tenella, Plasmodium spp. and Toxoplasma gondii, possess a homologous plastid-like organelle termed the apicoplast, derived from the endosymbiotic enslavement of a photosynthetic alga. However, currently no eimerian nuclear encoded apicoplast targeted proteins have been identified, unlike in Plasmodium spp. and T. gondii. In this study, we demonstrate that nuclear encoded enoyl reductase of E. tenella (EtENR) has a predicted N-terminal bipartite transit sequence, typical of apicoplast-targeted proteins. Using a combination of immunocytochemistry and EM we demonstrate that this fatty acid biosynthesis protein is located in the apicoplast of E. tenella. Using the EtENR as a tool to mark apicoplast development during the Eimeria lifecycle, we demonstrate that nuclear and apicoplast division appear to be independent events, both organelles dividing prior to daughter cell formation, with each daughter cell possessing one to four apicoplasts. We believe this is the first report of multiple apicoplasts present in the infectious stage of an apicomplexan parasite. Furthermore, the microgametes lacked an identifiable apicoplast consistent with maternal inheritance via the macrogamete. It was found that the size of the organelle and the abundance of EtENR varied with developmental stage of the E. tenella lifecycle. The high levels of EtENR protein observed during asexual development and macrogametogony is potentially associated with the increased synthesis of fatty acids required for the rapid formation of numerous merozoites and for the extracellular development and survival of the oocyst. Taken together the data demonstrate that the E. tenella apicoplast participates in type II fatty acid biosynthesis with increased expression of ENR during parasite growth. Apicoplast division results in the simultaneous formation of multiple fragments. The division mechanism is unknown, but is independent of nuclear division and occurs prior to daughter formation.
Assuntos
Eimeria tenella/metabolismo , Ácidos Graxos Dessaturases/metabolismo , Ácido Graxo Sintase Tipo II/metabolismo , Organelas/metabolismo , Sequência de Aminoácidos , Animais , Eimeria tenella/genética , Eimeria tenella/ultraestrutura , Ácidos Graxos Dessaturases/genética , Genes de Protozoários/genética , Genoma de Protozoário/genética , Células Germinativas/crescimento & desenvolvimento , Imuno-Histoquímica/métodos , Estágios do Ciclo de Vida , Merozoítos/ultraestrutura , Microscopia Eletrônica/métodos , Microscopia Imunoeletrônica/métodos , Dados de Sequência Molecular , Organelas/ultraestrutura , Filogenia , Esporozoítos/ultraestruturaRESUMO
We previously reported that 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) forms an interdigitated gel phase in the presence of 1-palmitoyl-sn-glycero-3-phosphocholine (16:0LPC) at concentrations below 30 mol%. In the present investigation, fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH), X-ray diffraction, and differential scanning calorimetry (DSC) were used to investigate the effect of cholesterol on the phase behavior of 16:0LPC/DPPC binary mixtures. At 25 degrees C, 30 mol% 16:0LPC significantly decreases the DPH fluorescence intensity during the transition of DPPC from the L(beta') phase to the L(betaI) phase. However, the addition of cholesterol to 16:0LPC/DPPC mixtures results in a substantial increase in fluorescence intensity. The changes in DPH fluorescence intensity reflect the probe's redistribution from an orientation parallel to the acyl chain to the center of the bilayer, suggesting a bilayer structure transition from interdigitation to noninterdigitation. The normal repeat period of small angle X-ray diffraction patterns can be restored and a reflection appears at 0.42 nm with a broad shoulder around 0.41 nm in wide angle X-ray diffraction patterns when 10 mol% cholesterol is incorporated into 30 mol% 16:0LPC/DPPC vesicles, indicating that the mixtures are in the gel phase (L(beta')). Moreover, DSC results demonstrate that 10 mol% cholesterol is sufficient to significantly decrease the main enthalpy, cooperativity and lipid chain melting of 30 mol% 16:0LPC/DPPC binary mixtures, which are L(betaI), indicating that the transition of the interdigitated phase is more sensitive to cholesterol than that of the noninterdigitated phase. Our data imply that the interdigitated gel phase induced by 16:0LPC is prevented in the presence of 10 mol% cholesterol, but unlike ethanol, an increasing concentration of 16:0LPC is not able to restore the interdigitation structure of the lipid mixtures.
Assuntos
Colesterol/farmacologia , Lisofosfatidilcolinas/química , Lisofosfatidilcolinas/metabolismo , Fosfatidilcolinas/química , Fosfatidilcolinas/metabolismo , 1,2-Dipalmitoilfosfatidilcolina/metabolismo , Varredura Diferencial de Calorimetria , Colesterol/metabolismo , Géis/química , Géis/metabolismo , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Espectrometria de Fluorescência , Temperatura , Difração de Raios XRESUMO
OBJECTIVE: To construct recombinant plasmid with human atrial natriuretic peptide (ANP) gene in fusion form for stable and high level expression of genetic engineering product ANP in E. coli system. METHODS: Plasmids with ANP fusion gene were constructed by PCR and sub-cloning and fusion protein was expressed in E. coli system. High level expression of the fusion genes was enhanced by linking operons in tandem. ANP was released from the fusion protein with thrombin treatment and purified by chromatography. Genetic-engineered ANP was evaluated with the drug production requirement, and produced ANP was tested for its effects of lowering blood pressure and diuresis in vivo and vasodilation in vitro. RESULTS: A series of 4 plasmid pCW111-114, containing 1 to 4 gene operons respectively, were constructed, and the yields of fusion protein were 46%, 54.8%, 56.1% and 60.1% of total cell protein. Fusion protein in the form of inclusion body was isolated and purified, and then treated with thrombin to release ANP. After purification using chromatography columns, at least 3 mg/L culture of ANP with the purity higher than 96% was produced in shaking flask. Primary pharmacological evaluation showed the produced ANP had the effects of blood pressure lowering in vivo and diuresis in vivo and vasodilation in vitro, which was similar to the activity of standard ANP. CONCLUSIONS: By the protocol of fusion gene cloning and expression, the human ANP was produced successfully in E. coli system.
Assuntos
Fator Natriurético Atrial/biossíntese , Animais , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/farmacologia , Escherichia coli/genética , Expressão Gênica , Engenharia Genética , Plasmídeos/genética , Ratos , Ratos Wistar , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/farmacologia , TrombinaRESUMO
OBJECTIVE: For further investigating the diagnostic value of the ECochG in Meniere's disease. METHOD: 112 vertigo patients including Meniere's disease, sudden deafness, cervical vertigo and other vertigo disease, had been done ECochG, glycerol test, audiometry and caloric test. The results were compared with those of normal group. RESULT: In Meniere's disease, the positive rate of abnormal-SP/AP in ECochG was 54.69% and the positive rate of glycerol test was 53.12%. There are no statistics difference (P > 0.05) between this two tests with X analysis. CONCLUSION: We think that the glycerol test and other relative examination are necessary for the diagnosis of Meniere's disease while the-SP/AP > 0.4 ms in the examination of ECochG.
Assuntos
Doença de Meniere/diagnóstico , Vertigem/diagnóstico , Adolescente , Adulto , Idoso , Audiometria de Resposta Evocada , Criança , Cóclea/fisiopatologia , Feminino , Glicerol , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We investigated the behavior of a membrane protein, Ca(2+)-ATPase, in interdigitated phospholipid bilayers. The results showed that Ca(2+)-ATPase does not cause significant alterations in the interdigitation of 16:0 LPC/DPPC (27.0 mol% LPC) vesicles when it is reconstituted with lipids. Intrinsic fluorescence, acrylodan fluorescent adducts, and CD spectra indicated that Ca(2+)-ATPase, when embedded in interdigitated bilayer structures, is more exposed to the hydrophilic environment and has a looser structure than when embedded in non-interdigitated bilayers. The interdigitation of acyl chains induces a rapid loss of enzyme activity. It is suggested that interdigitated bilayer structures may play an important role as negative regulatory factors in physiological functions.
Assuntos
ATPases Transportadoras de Cálcio/metabolismo , Bicamadas Lipídicas/metabolismo , 1,2-Dipalmitoilfosfatidilcolina/química , Animais , Dicroísmo Circular , Polarização de Fluorescência , Proteolipídeos/metabolismo , Coelhos , Retículo Sarcoplasmático/enzimologia , Espectrometria de Fluorescência , TemperaturaRESUMO
Anion transport activity and thermotropic behavior of Band 3 are found to be altered after binding of concanavalin (Con A) to human erythrocyte ghosts and isolated Band 3. At lower Con A concentration, the rate coefficients of anion transport enhance with increasing Con A concentration, while noticeable changes of the largest calorimetric endotherm of human erythrocyte membranes termed the C transition (Band 3) can not be observed. With 50 micrograms/ml of Con A, the rate coefficient of Con A-modified ghosts increases 34.4% in comparison with that of normal ghosts. Binding of Con A in lower concentration to ghosts bring about increase of fluidity of lipid which maybe contribute to increase anion transport via Band 3. At higher Con A concentration, the C transition tend to lower temperature with increase in Con A concentration, the C transition is shifted from 69.25 degrees C to 66.25 degrees C with 2.5 mg/ml Con A. It is suggested that the Con A-modified Band 3 possess a looser structure than normal one.
Assuntos
Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Concanavalina A/farmacologia , Membrana Eritrocítica/efeitos dos fármacos , Proteína 1 de Troca de Ânion do Eritrócito/química , Ânions/metabolismo , Transporte Biológico , Varredura Diferencial de Calorimetria , Membrana Eritrocítica/metabolismo , Polarização de Fluorescência , Humanos , Glicoproteínas de Membrana/química , Oligossacarídeos/química , TemperaturaRESUMO
AIM: This retrospective study was undertaken to analyze the outcome of hepatic resection in hepatocellular carcinomas (HCCs) that shrunk after transcatheter hepatic arterial chemoembolization (TACE) in 65 patients with unresectable HCCs between June 1987 and September 1996. MATERIALS AND METHODS: Among these 65 patients, the median diameter of the tumor was 9.9 cm (5.6-20.0) prior to the first TACE, after 1-6 times of TACE (median 3) the median tumor diameter reduced to 3.7 cm (1.9-12.5) prior to resection. The duration between the last TACE treatment and sequential resection varied from 1 to 9 months (median 2.5). Serum alpha-fetoprotein (AFP) levels were abnormal in 39 out of the 65 patients. In AFP producing HCCs, the AFP level returned to normal (=20 microgram/l) in 14 out of 39 patients (35.9%). Hepatic segmentectomy, multiple hepatic segmentectomy or partial hepatic resection were performed in 61 patients, right hemihepatectomy in 1, left trisegmentectomy in 2, and left hemihepatectomy in 1. RESULTS: Tumor necrosis ranged from 40 to 100% and pathologically and complete tumor necrosis occurred in 11 patients (16.9%). Of 14 patients with AFP levels decreased to normal, 10 still had microscopic living tumor foci. The 1-, 3- and 5-year survival rates of the 65 patients were 80.0, 65.0 and 56.0% respectively. CONCLUSION: TACE treatment can provide a chance of tumor resection for those patients with initially judged unresectable HCCs, and liver resection should be performed when the tumor has shrunk to be resectable, even when the AFP level has returned to normal.
Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Cuidados Paliativos/métodos , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Terapia Combinada , Feminino , Hepatectomia/métodos , Humanos , Testes de Função Hepática , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Resectional therapy has been accepted as the only curative therapy for hepatocellular carcinoma (HCC). Unfortunately, it is estimated that only 10% of HCC are resectable at the time of diagnosis. Cytoreduction and sequential resection offer a new hope for patients with unresectable HCC. Radioimmunotherapy (RIT) is an attractive approach for cytoreduction. We have previously shown that intrahepatic arterial 131I-labelled anti-HCC monoclonal antibody (131I-Hepama-1 mAb) could be used safely in combination with hepatic artery ligation for treatment of unresectable HCC, and encouraging results have been achieved. In this paper, the long-term survival and the prognostic factors in HCC patients treated with radioimmunotherapy will be analysed. Sixty-five patients with surgically verified unresectable HCC were treated with hepatic artery ligation plus hepatic artery cannulation and infusion from 1990 to 1992. Thirty-two patients were enrolled in a phase I-II clinical trial with infusion of 131I-radiolabelled anti-HCC monoclonal antibody (Hepama-1 mAb) via the hepatic artery (the RIT group). Another 33 patients formed the group treated with intrahepatic-arterial chemotherapy (the non-RIT group). T cell subsets were measured in 24 patients and human anti-(murine Ig) antibody (HAMA) were monitored in the RIT group. The 5-year survival rate was significantly higher in the RIT group than in the chemotherapy group, being 28.1% compared to 9.1% (P < 0.05); this was mainly a result of better cytoreduction and a higher sequential resection rate (53.1% compared to 9.1%). Significant prognostic factors in the RIT group included tumour capsule status and the number of tumour nodules. HAMA incidence and CD4+ T lymphocytes influenced short-term, but not long-term survival. It is suggested that intrahepatic-arterial RIT, using 131I-Hepama-1 mAb, combined with hepatic artery ligation might be an effective approach to improve long-term survival in some patients with unresectable HCC, which may successfully be made resectable by intra-arterial infusion of 131I-Hepama-1 mAb.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/radioterapia , Radioisótopos do Iodo/uso terapêutico , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/radioterapia , Radioimunoterapia/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do TratamentoRESUMO
The oxidation reactions of three substrates, p-hydroxybenzoic acid (HBA), p-hydroxyphenylacetic acid, and p-hydroxyphenylpropionic acid, with H2O2 catalysed by hemin were studied. It was significant that only the oxidation product of HBA, di-p,p'-hydroxybenzoic acid, forms a long-lived fluorescent complex with Tb3+. The three substrates themselves do not form fluorescent complexes with Tb3+ although they have chemical structural similarities. Based on this, a novel lanthanide fluorescence system with a coupled reaction was developed. The possible reactive mechanism is discussed. HBA was concluded to be well suited to several types of application from hemin determination to bovine serum albumin labeling.
Assuntos
Fluorimunoensaio/métodos , Hemina , Metais Terras Raras , Catálise , Soroalbumina BovinaRESUMO
In the author's institution, 2254 patients with hepatocellular carcinoma (HCC) have been treated during 1958-1994. The overall 5-year survival increased from 5.4% (1958-1970), to 11.9% (1971-1982), to 46.2% (1983-1984), which correlated well with the increasing proportion of small HCC in the series (2.6%, 12.1%, and 33.4%, respectively); with the increasing percentage of limited resection (3.1%, 32.2%, and 58.3%); with the increasing number of re-resections for recurrence (0, 27, and 114 patients); and with the increasing number of second stage resections (0, 5, and 67 patients). In our institution, surgical approaches that resulted in significantly prolonging survival included: small HCC resection, re-resection, and cytoreduction followed by sequential resection for initially unresectable HCC. Experience in these 3 aspects suggests: (a) Small HCCs are mainly found by screening using AFP and ultrasonography (US) in a high risk population, and limited resection is the best treatment in patients with compensated liver cirrhosis, the 5-year survival after resection being 62.9% (n = 549). (b) Postoperative monitoring using AFP/US every 2-3 months for 5-10 years after curative resection is needed to detect subclinical recurrence. Limited re-resection is indicated for liver recurrence less than 3 nodules, and lung lobectomy is of proven merit to prolong survival for solitary lung metastasis. Re-resection of subclinical recurrence has resulted in a 10-20% further increase in 5-year survival after curative resection. (c) Palliative surgery other than resection such as hepatic artery ligation (HAL) and cannulation with arterial infusion (HAI), cryosurgery, etc. are superior to palliative resection with residual cancer. (d) Cytoreduction and sequential resection have provided hope for localized unresectable HCC, particularly in the right cirrhotic liver. Multimodality combination treatments such as HAL+HAI+radioimmunotherapy/regional radiotherapy are acceptable cytoreductive therapies. Repeated transcatheter hepatic arterial chemoembolization (TACE) is an alternative nonsurgical approach. Sequential resection is important to eradicate residual cancer after cytoreduction. The 5-year survival of 72 patients with cytoreduction and sequential resection for initially unresectable HCC was 62.1% and resulted in improving 5-year survival in the entire series of unresectable HCC over the 3 periods from 0% to 7.4% to 25.7%, respectively. However, multicentric origin and tumor invasiveness are two major targets to be studied in the control of recurrence and metastasis.
Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Previsões , Hepatectomia/tendências , Humanos , Fígado/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Reoperação , Taxa de SobrevidaRESUMO
We have previously demonstrated that syngeneic marrow mixed with H-2 haploidentical marrow transplantation could provide not only protection against graft-versus-host disease (GVHD) but also anti-leukemic (GVL) effects in mice. In the present studies, we report clinical observations using autologous marrow mixed with HLA-haploidentical allogeneic marrow transplantation for treatment of patients with malignant blood diseases. Sixteen cases, including 12 with acute leukemia and four with advanced malignant lymphoma, were treated by autologous marrow, which was purged in vitro by hyperthemia (42.5 degrees C for 70 min) following incubation for 5 days with interleukin 2 (IL-2) in liquid culture and mixed with HLA haploidentical marrow cells from their sibling or parent. Acute GVHD was not observed in any patient after transplantation. Hematological rescue in the clinical setting was demonstrated in all cases but one who died early from hepatic veno-occlusive disease (VOD). Five cases who were transplanted at the time of CR2 or CR3 and in advanced phase of lymphoma, relapsed 4 to 7 months after transplantation. The relapse rate was 31.3%. None of eight patients who received allogeneic BMT within 2 h after ABMT relapsed with median follow-up of 12 months and two of them died from procedure-related complications. Seven cases are still alive and disease-free with a median follow-up of 12 months. Mixed chimerism was found in 3/6 cases, who had different sex donors, by analysis of sex chromosomes. These results show that mixed transplantation is a safe, effective and new approach to treating patients with malignant tumors. In order to detect the effects of GVL, studies are now in progress in our clinic.
Assuntos
Transplante de Medula Óssea , Neoplasias Hematológicas/terapia , Adulto , Animais , Feminino , Antígenos HLA , Teste de Histocompatibilidade , Humanos , Masculino , Camundongos , Transplante Autólogo , Transplante Homólogo , Resultado do TratamentoRESUMO
The viral proteins E1 and E2 are essential for the replication of the HPV-11 origin. We have now mapped the E1 binding site (E1BS) and show by mutation analysis that the E1BS and an adjoining poly(A)-rich region are necessary for efficient replication of the origin. We have also shown, using suboptimal levels of E1 protein, that enhancement of E1 binding by E2 partially protects the E1BS. Finally, we show that E1 can enhance the binding of E2 even in the absence of the E1BS.
Assuntos
DNA Viral/biossíntese , Proteínas de Ligação a DNA/metabolismo , Papillomaviridae/genética , Origem de Replicação/genética , Proteínas Virais/metabolismo , Sequência de Bases , Sítios de Ligação , Pegada de DNA , DNA Ribossômico/genética , DNA Viral/genética , Humanos , Dados de Sequência Molecular , Mutação , Papillomaviridae/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Sequências Reguladoras de Ácido NucleicoRESUMO
During 1958-1993, 2030 patients with pathologically proven primary liver cancer (PLC) were retrospectively reviewed. Comparison between small PLC (< or = 5 cm, n = 514) and large PLC (> 5 cm, n = 1516) revealed that small PLC had a higher resection rate (92.4% versus 49.1%), lower operative mortality (1.7% versus 5.2%), a higher percentage of single tumour nodules (78.0% versus 53.4%), a higher percentage of well encapsulated tumour (74.5% versus 35.8%) and higher survival rates after resection (5-year, 63.8% versus 36.6%; 10-year, 46.8% versus 28.5%). No significant difference was found between survival following limited resection (n = 440) and lobectomy (n = 34) in patients with small PLC. Re-resection of any subclinical recurrence or solitary pulmonary metastasis after small PLC resection was done in 70 cases. These results indicate that resection is still the modality of choice for treatment of small PLC; limited resection instead of lobectomy was the key to increasing resectability and decreasing operative mortality; re-resection of subclinical recurrence was important to prolong survival further.
Assuntos
Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
The poor prognosis of hepatocellular carcinoma (HCC) was partly a result of the majority of unresectable HCCs in clinical patients. Fortunately, with the progress of regional cancer therapies and multimodality treatment, some of the localized unresectable HCCs were converted to resectable ones. During the period 1960-1994, 72 of the 663 patients with surgically verified unresectable HCCs have been converted to resectable. Successful cytoreduction with median diameter reduced from 10 cm to 5 cm was mainly a result of the triple or double combination treatment with hepatic artery ligation, hepatic artery cannulation with infusion, radioimmunotherapy, and fractionated regional radiotherapy. The interval between the first operation and the sequential resection was 5 months. The operative mortality was 1.4% for sequential resection, and the 5-year survival was 62.1%. Analysis of factor influencing sequential resection rate revealed HCCs that were single nodule, well encapsulated, situated at right lobe or hepatic hilum, associated with micronodular cirrhosis, and treated with triple or double combination modalities had higher sequential resection rate as compared to their counterparts. Analysis of factors influencing survival after sequential resection revealed that HCCs with a solitary tumor confined in one lobe, without tumor embolus, and without residual cancer in specimen of sequential resection, had longer survival. It is suggested that localized unresectable, solitary, well encapsulated, right lobe or hilar HCC, associated with micronodular cirrhosis, will be good candidates for cytoreduction and sequential resection; and HCCs with unilateral involvement, without tumor embolus, and with complete necrosis of tumor after multimodality treatment favored better prognosis.
Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/cirurgia , Terapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , PrognósticoRESUMO
To investigate the clinicopathologic characteristics of primary liver cancer (PLC) in young adults, 77 patients aged 35 or younger were compared with 603 patients older than 35 years during the same period. In the young patients, PLC showed: (1) a low incidence detected at mass survey (young 15.6% vs older 28.7%, P < 0.05); (2) a low level of history of hepatitis (young 36.8% vs older 66.3%, P < 0.01); (3) a high incidence of positivity for hepatitis B surface antigen (HBsAg) (young 79.2% vs older 67.6%, P < 0.05); (4) a relatively low incidence of associated cirrhosis (young 64.9% vs older 90.7%, P < 0.01); (5) larger tumor size (PLC > 5 cm; young 87.0% vs older 73.0%, P < 0.01); and (6) a more advanced stage of the disease according to the TNM classification (stage III; young 29.9% vs older 18.2%, P < 0.05). It is suggested that hepatitis B virus (HBV) may play an important role in the development of PLC without associated liver cirrhosis in young patients. Close periodic surveillance of young adults who are positive for HBsAg is important to detect PLC at an early stage.
Assuntos
Neoplasias Hepáticas/epidemiologia , Adulto , Fatores Etários , Idoso , China/epidemiologia , Feminino , Humanos , Incidência , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
This paper reports the long-term results of multimodality treatment in 1639 patients with pathologically proven primary liver cancer (PLC) over the past three decades. In this series, patients in subclinical stage constituted 23.9% (391/1639), moderate stage 63.0% (1032/1639), and late stage 13.2% (216/1639). There were 381 patients (23.2%) with small PLC (< = 5 cm). The PLC was coexistent with liver cirrhosis in 86.4% (1416/1639). The 5-year survival after resection of PLC was 45.5% for the whole series (n = 896), and 62.7% for patients with a tumor < = 5 cm (n = 345). The 5-year survival after hepatic artery ligation (HAL) and hepatic artery infusion (HAI) (n = 124) was 18.1%, while the 5-year survival after palliative resection (n = 175) was 12.5%. The 5-year survival of 40 patients receiving second-look resection after cytoreduction therapy was 68.4%. Cryosurgery was performed on 107 PLC patients, the 5-year survival being 22.0% for the whole series, and 48.8% for the 32 patients with small PLC. The 5-year recurrence rate after resection was 55.3%. The 5-year survival after reoperation for recurring tumor (n = 90) was 40.8%. It is suggested that surgery remains the modality of choice, and it plays a more important role in the treatment of PLC. The results of palliative surgery (HAL + HAI) seem better than those of palliative resection; combined multimodality treatment and second-look resection, and new surgical techniques might offer hope for unresectable advanced PLC.