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1.
J Cosmet Dermatol ; 19(9): 2421-2427, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31901006

RESUMO

BACKGROUND: Numerous researches have focused on discovering available inhibitors of melanogenesis from natural medicinal plants with stable efficacy and safety to resolve cutaneous hyperpigmentary problems. Melochia corchorifolia Linn. (MC) has been used as folk medicine to treat various diseases. However, the effect of MC on melanogenesis remains unknown. AIM: In this study, we investigated the effect of MC extract on melanogenesis and its underlying mechanisms in B16F10 mouse melanoma cells. METHODS: B16F10 cells were treated with MC extract, and then, cell viability, melanin content, and tyrosinase activity were analyzed. The mRNA and protein expression of tyrosinase and microphthalmia-associated transcription factor (MITF) were evaluated using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. Phosphorylated or total protein levels in MC extract-induced signaling pathways were analyzed by Western blotting. RESULTS: Treatment of B16F10 cells with MC extract inhibited melanin synthesis and intracellular tyrosinase activity in a dose-dependent manner with no cytotoxicity. Protein and mRNA expressions of tyrosinase and MITF were also significantly decreased by MC extract treatment. In addition, phosphorylated level of extracellular signal-regulated kinase (ERK) was obviously increased by MC extract, but AKT pathway was not activated. Inhibited ERK phosphorylation by pretreatment with a selective ERK inhibitor PD98059 significantly reversed the decreased melanin content induced by treatment with MC extract in B16F10 cells. CONCLUSION: MC extract inhibits melanogenesis in B16F10 mouse melanoma cells through suppression of MITF-tyrosinase signaling pathway by ERK activation.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular , Malvaceae/química , Melanoma Experimental , Extratos Vegetais/uso terapêutico , Transdução de Sinais , Animais , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Melaninas , Melanoma Experimental/tratamento farmacológico , Camundongos , Monofenol Mono-Oxigenase/genética , Monofenol Mono-Oxigenase/metabolismo
2.
Oncotarget ; 8(42): 71699-71708, 2017 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-29069739

RESUMO

BACKGROUND: Representative data on the gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) in Asian patients is rare, especially in China. This study aims to create a GEP-NENs profile of Chinese patients. METHODS: This was a hospital-based, nation-wide, and multi-center 10-year (2001-2010) retrospective study which collected GEP-NEN patients' information in tertiary referral hospitals. All 2010 inpatient GEP-NEN cases with confirmed pathology in the selected hospitals were included. The primary GEP-NEN sites were measured and the epidemiological and clinical information of each tumor site were compared. RESULTS: The most common primary sites for GEP-NEN were the pancreas (31.5%) and rectum (29.6%), followed by the cardia (11.6%) and body (15.4%) of stomach. Small intestinal and colonic NENs took up a relatively small proportion of all patients. Pancreatic and rectal NENs, rather than cardiac and gastric body NENs, tended to be found in younger (P<0.001), female (P<0.001), urban (P<0.001) residents with a higher education level (P=0.032) and were also diagnosed at earlier stage (P<0.001) and lower grade (P<0.001). Surgery remained the primary treatment method in all groups. CONCLUSIONS: More studies on the commonality and heterogeneity of GEP-NENs are warranted to improve diagnosis efficiencies and treatment outcomes.

3.
Medicine (Baltimore) ; 95(46): e5393, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27861374

RESUMO

Treatment algorithm has not been established for early gastric cancer with signet ring cell carcinoma (SRC), which has a reported low rate of lymph node metastasis (LNM) similar to differentiated cancer. A cohort of 256 patients with early gastric SRC at our center between January 2002 and December 2015 were retrospectively reviewed. Multivariate logistic regression analysis was used to determine the independent factors of LNM. A nomogram for predicting LNM was constructed and internally validated. Additional external validation was performed using the database from Cancer Institute Ariake Hospital in Tokyo (n = 1273). Clinical performance of the model was assessed by decision analysis of curve. The overall LNM incidence was 12.9% (33/256). The multivariate logistic model identified sex, tumor size, and LVI as covariates associated with LNM. Subsequently, a nomogram consisted of sex, tumor size, and depth of invasion was established. The model showed qualified discrimination ability both in internal validation (area under curve, 0.801; 95% confidence interval [CI], 0.729-0.873) and in external dataset (area under curve, 0.707; 95% CI, 0.657-0.758). Based on the nomogram, treatment algorithm for early gastric SRC was proposed to assist clinicians in making better decisions. We developed a nomogram predicting risk of LNM for early gastric SRC, which should be helpful for patient counseling and surgical decision-making.


Assuntos
Carcinoma de Células em Anel de Sinete , Ressecção Endoscópica de Mucosa/métodos , Gastrectomia/métodos , Linfonodos/patologia , Nomogramas , Medição de Risco/estatística & dados numéricos , Neoplasias Gástricas , Idoso , Algoritmos , Carcinoma de Células em Anel de Sinete/patologia , Carcinoma de Células em Anel de Sinete/cirurgia , China , Tomada de Decisão Clínica/métodos , Feminino , Humanos , Japão , Funções Verossimilhança , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
4.
Biochem Biophys Res Commun ; 477(3): 336-42, 2016 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-27343558

RESUMO

Vasoactive intestinal peptide (VIP), one of the major skin neuropeptides, has been suggested to have active roles in the pathogenesis of inflammatory skin disorders such as atopic dermatitis and psoriasis, which can commonly cause post-inflammatory hyperpigmentation. However, the effect of VIP on melanogenesis remains unknown. In this study, we showed that the melanin contents, tyrosinase activity, and gene expression of tyrosinase and microphthalmia-associated transcription factor (MITF) were significantly increased by treatment with VIP in B16F10 mouse melanoma cells and the stimulatory melanogenic effect was further examined in human epidermal melanocytes (HEMns). In addition, phosphorylated levels of CRE-binding protein (CREB) and protein kinase A (PKA) were markedly increased after VIP treatment, but not p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK), or Akt, indicating the possible PKA-CREB signaling pathway involved in VIP-induced melanogenesis. This result was further verified by the fact that VIP induced increased melanin synthesis, and protein levels of phosphorylated CREB, MITF, tyrosinase were significantly attenuated by H89 (a specific PKA inhibitor). These data suggest that VIP-induced upregulation of tyrosinase through the CREB-MITF signaling pathway plays an important role in finding new treatment strategy for skin inflammatory diseases related pigmentation disorders.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Melaninas/biossíntese , Melanoma Experimental/metabolismo , Fator de Transcrição Associado à Microftalmia/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Transdução de Sinais , Peptídeo Intestinal Vasoativo/farmacologia , Animais , Melanoma Experimental/patologia , Camundongos , Fator de Transcrição Associado à Microftalmia/genética , RNA Mensageiro/genética
5.
Tumour Biol ; 36(11): 8379-87, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26018507

RESUMO

Ubiquitin C-terminal hydrolase-L1 (UCHL1) is a de-ubiquitinating enzyme, which enzymatic activity relies on the C90 site. The function of UCHL1 is controversial in different types of cancer, and its role in gastric cancer progression remains unclear. In this study, immunohistochemistry staining was applied to detect the expression of UCHL1 in primary gastric cancer and liver metastases from gastric cancer. MKN45 and BGC823 cell lines with stable expression of de-ubiquitinase active UCHL1 or inactive UCHL1-variant C90S were established by lentiviral infection. The effect of UCHL1 on cell proliferation was evaluated by MTT and colony formation assays. The abilities of cell migration and invasion were determined by transwell assay. Protein expression levels were determined by Western blot. The results indicated that UCHL1 had a significantly higher positive expression rate in liver metastases from gastric cancer compared with primary gastric cancer. Overexpression of UCHL1 in MKN45 and BGC823 cells promoted cell proliferation, migration, and invasion depending on its de-ubiquitinase activity. UCHL1 activated Akt and Erk1/2, which process also required enzymatic activity and was necessary for mediating cell migration and invasion. These findings demonstrated that UCHL1 promoted cell proliferation, migration, and invasion depending on its de-ubiquitinase activity by activating Akt and Erk1/2, which may account for its higher positive expression rate in liver metastases from gastric cancer. UCHL1 could be a candidate biomarker and a therapeutic target for gastric cancer metastasis.


Assuntos
Neoplasias Hepáticas/genética , Invasividade Neoplásica/genética , Neoplasias Gástricas/genética , Ubiquitina Tiolesterase/biossíntese , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Sistema de Sinalização das MAP Quinases , Masculino , Invasividade Neoplásica/patologia , Metástase Neoplásica , Proteína Oncogênica v-akt/genética , Transdução de Sinais , Neoplasias Gástricas/patologia , Ubiquitina Tiolesterase/genética
6.
J Cancer Res Clin Oncol ; 141(6): 1037-47, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25432142

RESUMO

PURPOSE: Nuclear apoptosis-inducing factor 1 (NAIF1) could induce apoptosis in gastric cancer cells. Previously, we have reported that the expression of NAIF1 protein is down-regulated in gastric cancer tissues compared with the adjacent normal tissues. However, the role of NAIF1 in gastric cancer cells is not fully understood. METHODS: The effects of NAIF1 on cell viability were evaluated by MTT and colony formation assays. The ability of cellular migration and invasion were analyzed by transwell assays. The expression levels of targeted proteins were determined by western blot. The relative RNA expression levels were analyzed using quantitative polymerase chain reaction assays. Xenograft experiment was employed to determine the anti-tumor ability of NAIF1 in vivo. RESULTS: The study demonstrates that transient transfection of NAIF1 in gastric cancer cells BGC823 and MKN45 could inhibit the cell proliferation, migration, and invasion of the two gastric cancer cell lines. The tumor size is smaller in NAIF1-overexpressed MKN45 cell xenograft mice than in unexpressed group. Further in-depth analysis reveals that NAIF1 reduces the expression of MMP2 as well as MMP9, and inhibits the activation of FAK, all of which are key molecules involved in regulating cell migration and invasion. In addition, NAIF1 inhibits the expression of c-Jun N-terminal kinase (JNK) by accelerating its degradation through ubiquitin-proteasome pathway. Meanwhile, NAIF1 reduces the mRNA and protein expression of ERK1/2. CONCLUSIONS: Our study revealed that NAIF1 plays a role in regulating cellular migration and invasion through the MAPK pathways. It could be a therapeutic target for gastric cancer.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Proteínas Nucleares/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Actinas/metabolismo , Animais , Proteínas Reguladoras de Apoptose/farmacologia , Western Blotting , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Progressão da Doença , Quinase 1 de Adesão Focal/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Invasividade Neoplásica , Proteínas Nucleares/farmacologia , Fosforilação , Complexo de Endopeptidases do Proteassoma/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Gástricas/enzimologia , Ubiquitina/metabolismo
7.
Dermatol Surg ; 40(5): 545-52, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24645970

RESUMO

BACKGROUND: Ablative 10,600-nm carbon dioxide (CO2 ) fractional laser treatments have shown favorable outcomes for atrophic acne scars. OBJECTIVE: To compare the efficacy and complications of fractional CO2 laser treatments with different fluences and densities for acne scars. METHODS: Twenty patients were treated using a single session of fractional CO2 laser in Deep FX mode. In Group A (n = 10), half of the face was treated with 20 mJ, density 10% and the other half with 20 mJ, density 20%. In Group B (n = 10), half of the face was treated with 10 mJ, density 10% and the other half with 20 mJ, density 10%. Patients were evaluated at baseline and 3 days, 1 week, 1 month, and 3 months after the procedure. RESULTS: There was no significant difference in efficacy between different laser settings within the groups, although adverse effects were more evident in patients treated with higher densities or fluences. CONCLUSION: Factional CO2 laser treatment using the Deep FX mode may provide a significant efficacy with lower fluence and density with fewer complications than with higher energies for acne scars.


Assuntos
Cicatriz/patologia , Cicatriz/cirurgia , Técnicas Cosméticas , Lasers de Gás/uso terapêutico , Acne Vulgar/complicações , Adulto , Atrofia , Cicatriz/etiologia , Técnicas Cosméticas/efeitos adversos , Face , Feminino , Humanos , Terapia a Laser/efeitos adversos , Terapia a Laser/métodos , Lasers de Gás/efeitos adversos , Masculino , Satisfação do Paciente , Adulto Jovem
8.
Zhonghua Zhong Liu Za Zhi ; 35(4): 292-4, 2013 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-23985259

RESUMO

OBJECTIVE: To analyze the clinical data and prognosis of gastric small cell carcinoma (GSCC), summarize recent progress in diagnosis and therapy of this disease reported in the literature, and to provide the theoretical basis for its appropriate treatment. METHODS: Clinicopathological data of 17 patients with pathologically confirmed GSCC, treated in our hospital between 1999 to 2012, were retrospectively reviewed. RESULTS: There were 16 males and 1 female, ranged from 46 to 75 years (mean 64.6 years). The tumor was located in the gastric cardia in 13 cases, three in the gastric fundus, and one in the gastric body. All the 17 patients received surgery and 10 of them received postoperative adjuvant chemotherapy, one received preoperative adjuvant chemotherapy. Thirteen patients were followed up. Among them, two 1ived for 40 months all along, the other 3 cases died of recurrence and extensive metastasis in 6 month after operation. The median survival was 13.0 months. The median survival of the patients with and without lymph node metastasis were 42 months and 13 months, respectively. The median survival time of stage II and III patients were 24 months and 14 months, respectively. CONCLUSIONS: It is difficult to make a definite diagnosis before or during the operation for GSCC. Radical operation could be done according to other gastric cancers and lymph node dissection could be simplified. Postoperative chemotherapy with the same scheme as lung small cell carcinoma may help to improve the outcome and prolong the survival of the patients.


Assuntos
Carcinoma de Células Pequenas , Neoplasias Gástricas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/cirurgia , Quimioterapia Adjuvante , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Gastrectomia/métodos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Células Neoplásicas Circulantes , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida
9.
Zhonghua Zhong Liu Za Zhi ; 35(4): 305-8, 2013 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-23985262

RESUMO

OBJECTIVE: To summarize and analyze the diagnosis, clinical features and therapy of primary colorectal non-Hodgkin's lymphoma (NHL). METHODS: The clinicopathological data of 52 patients with primary colorectal NHL diagnosed and treated in our department from January 2000 to January 2010 were reviewed and analyzed retrospectively in this study. RESULTS: This group of patients was composed of 45 cases of B cell and 7 T cell lymphomas, including 33 males and 19 females, with a male to female ratio of 1.7:1, and the age at diagnosis was 16 - 74 years old, with a median age of 50 years. The ileocecal region was most frequently involved site, acounted for 48.1%. The common symptoms encountered were abdominal pain (66.7%), diarrhea (15.6%), blood stool (24.4%), and body weight loss (8.9%). All patients were eventually diagnosed by histopathology, and the DLBCL subtype took up 64.4%. Among the 45 cases of B cell subtype, 33 cases (73.3%) were of early stage (IE and IIE confirmed), and the 5-year survival rate was 78.1%, while those of stage IIIE and IVE comprised 26.7%, with a 5-year survival rate of 45.5% (P < 0.05). The 5-year survival rate of all patients was 71.1%. Surgery was employed in 36 cases, and 9 patients received chemotherapy alone. Radical surgery could significantly increase the patients' overall survival rate, as compared with the chemotherapy alone group and palliative surgery group (P < 0.05). CONCLUSIONS: Colorectal non-Hodgkin's lymphoma is a rare malignancy of the gastrointestinal tract. B cell type, male predominance and DLBCL subtype are most encountered manifestations in clinics. Multi-modality management with radical surgical resection of the primary lesion followed by standard chemotherapy, affords better local disease control, and a better survival outcome. Early detection and tailored immunotherapy can obviously prolong the long-term survival time.


Assuntos
Neoplasias Colorretais , Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Humanos , Linfoma de Células B/diagnóstico , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/patologia , Linfoma de Células B/cirurgia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/cirurgia , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/cirurgia , Linfoma de Células T/diagnóstico , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/patologia , Linfoma de Células T/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/uso terapêutico , Estudos Retrospectivos , Terapia de Salvação , Taxa de Sobrevida , Vincristina/uso terapêutico , Adulto Jovem
10.
Cancer Biol Med ; 10(2): 86-91, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23882423

RESUMO

OBJECTIVE: This study aims to explore the clinicopathologic characteristics and prognostic factors of gastric cancer patients with metachronous ovarian metastasis. METHODS: Clinicopathologic data were collected from 63 post-operative gastric cancer patients with metachronous ovarian metastasis. The patients were admitted to the Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College between January 1999 and December 2011. A log-rank test was conducted for survival analysis. Possible prognostic factors that affect survival were examined by univariate analysis. A Cox regression model was used for multivariate analysis. RESULTS: The incidence of ovarian metastasis was 3.4% with a mean age of 45 years. Up to 65.1% of the patients were pre-menopausal. The mean interval between ovarian metastasis and primary cancer was 16 months. Lowly differentiated carcinoma ranked first in the primary gastric cancers. The majority of lesions occurred in the serous membrane (87.3%). The metastatic sites included N2-3 lymph nodes (68.3%), bilateral ovaries (85.7%), and peritoneal membrane (73%). Total resection of metastatic sites was performed (31.7%). The overall median survival was 13.6 months, whereas the overall 1-, 2-, and 3-year survival rates were 52.5%, 22.0%, and 9.8%, respectively. The 5-year survival rate was zero. Univariate analysis showed that the patient prognosis was correlated with metastatic peritoneal seeding, vascular tumor embolus, range of lesion excision, and mode of comprehensive treatment with adjuvant chemotherapy (P<0.05). Multivariate analysis indicated that metastatic peritoneal seeding was an independent prognostic factor for gastric cancer patients with ovarian metastasis (P<0.01). CONCLUSION: Effective control of peritoneal seeding-induced metastasis is important for improving the prognosis of gastric cancer patients with ovarian metastasis.

11.
Zhonghua Wai Ke Za Zhi ; 51(3): 225-9, 2013 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-23859323

RESUMO

OBJECTIVE: To summarize and analyze the clinical feature, therapeutic methods and prognosis of gastric small cell carcinoma (SCC). METHODS: The clinical and pathological data of 41 patients diagnosed of gastric SCC were analyzed in this research. Also, the factors which may potentially affect the patients' survival outcome were evaluated. There were 35 male and 6 female patients. The age at diagnosis was 39-84 years, median age was 62 years. The 31 cases (75.6%) of gastric SCC patients were involved in the upper third of the stomach, 3 cases (7.3%) in the middle, 7 cases (17.1%) in the lower third. RESULTS: The time from the event of symptoms to final confirmation was 1 to 13 months, the median time was 3 months. The longest diameter of tumors was from 2.5 to 15.0 cm, the average was 6.5 cm. The 38 cases (92.7%) chosed surgery as the first treatment, among which 25 cases (61.0%) were performed radical tumor resection, 13 cases (31.7%) went through palliative resection, and 3 cases (7.3%) just employed chemotherapy. The initial II, III, IV stage were 2, 31 and 8 cases, respectively. The overall median survival time was 19 months, median disease free survival time was 11 months, 1-, 2-, 5-years survival rates were 70.7%, 46.3% and 36.6%, respectively. In univariate survival analysis, the tumor size (χ² = 5.565), change of the body weight (χ² = 3.688), type of operation (χ² = 11.747) and relapse or not (χ² = 17.966) were obviously correlaed with the prognosis (P < 0.05). CONCLUSIONS: Gastric SCC is a rare disease of the gastrointestinal tract, the misdiagnosis rate is high, and the prognosis is dismal. Muti-modality management, with radical surgical resection of the primary lesion followed by standard adjuvant-chemotherapy, affords better local disease control and a better survival outcome.


Assuntos
Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Pequenas/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/terapia , Taxa de Sobrevida
12.
Zhonghua Yi Xue Za Zhi ; 92(24): 1677-80, 2012 Jun 26.
Artigo em Chinês | MEDLINE | ID: mdl-22944157

RESUMO

OBJECTIVE: To evaluate the efficacy and safety profile and to explore the role of docetaxel, S-1 plus cisplatin (DCS) or oxaliplatin (DOS) in the treatment of advanced gastric cancer. METHODS: A total of 45 patients with advanced gastric cancer were recruited. They received DCS or DOS at the discretion of investigators. Docetaxel was given intravenously at the dose of 60 mg/m² at d1, S-1 60 mg×m⁻²×d⁻¹ or 80 - 120 mg/d according to individual patient's area of body surface orally from d1 to d14 and cisplatin 30 mg/m² at d1, d2 or oxaliplatin 111 - 127 (median: 117) mg/m ²at d2. Each cycle was for 21 days. RESULTS: Forty-three patients received ≥ 1 complete cycle of DCS/DOS with a median cycle number of 5(range: 1 - 8). Among 42 patients evaluated for efficacy, the outcomes were partial response (n = 28), stable disease (n = 9) and progression (n = 5). The response rate was 66.7%. Progression-free survival (PFS) of 32 patients on chemotherapy alone was 7.1 months and the median overall survival (OS) was not reached. The most common grade 3/4 adverse effects included neutropenia (46.5%), thrombocytopenia (9.3%), vomiting (9.3%), nausea (7.0%) and diarrhea (4.7%). Ten of fourteen patients with advanced unresectable gastric cancer without clinically detectable distant metastases underwent surgical resection after a median of 4 (2-6) cycles of DCS or DOS and 9 (64.3%) had R0 resection. CONCLUSIONS: DCS/DOS is effective for advanced gastric cancer and in the setting of neoadjuvant chemotherapy. And the toxicities of DCS/DOS are manageable.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Adulto , Idoso , Docetaxel , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ácido Oxônico/administração & dosagem , Platina/administração & dosagem , Taxoides/administração & dosagem , Tegafur/administração & dosagem , Resultado do Tratamento
13.
Mol Biol Rep ; 37(5): 2189-98, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19680787

RESUMO

Phosphatidylinositol-4-phosphate 5-kinase-like 1 (PIP5KL1), the forth member of phosphatidylinositol-4-phosphate 5-kinases (PIPKs) type I, acts as a scaffold for localization and activation of PIPKs, which mediates numerous cellular processes. However, the role of PIP5KL1 in the development of human cancer is still lacking. We therefore examined the expression of PIP5KL1 in human normal and cancer tissues by tissue microarrays (TMAs). Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence imaging analysis were used to testify the mRNA and protein levels of PIP5KL1 in human gastric cancer cell line (BGC823). The cell proliferation was investigated with 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay. Both wound healing and transwell migration assay were performed to study the cell migration. The phosphorylation of v-akt murine thymoma viral oncogene homolog 1 (AKT1) was determined by western immunoblot analysis. Immunostaining of gastric cancer tissue microarrays revealed a negative correlation between PIP5KL1 overexpression and gastric cancer in situ. Transient transfection PIP5KL1 induced a significant increase expression at both transcriptional and translational levels and consequent robust inhibition of proliferation (P < 0.05) and migration (P < 0.05) of BGC823 cells. Overexpression of PIP5KL1 markedly inhibited (P < 0.05) serum-induced phosphorylation of AKT1. Taken together, these studies indicate a functional negative correlation between elevated levels of PIP5KL1 and the development of human gastric cancer, suggesting that PIP5KL1 overexpression may suppress gastric cancer formation.


Assuntos
Movimento Celular , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Mucosa Gástrica/enzimologia , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Fosforilação , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Transporte Proteico , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Soro , Neoplasias Gástricas/genética , Frações Subcelulares/enzimologia , Análise Serial de Tecidos , Cicatrização
14.
Ai Zheng ; 25(8): 974-8, 2006 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-16965677

RESUMO

BACKGROUND & OBJECTIVE: Little evidence is known from experimental research for intraoperative hyperthermic intraperitoneal chemotherapy. This study was to investigate the effect of hyperthermic chemotherapy on gastrointestinal cancer cells in vitro and explore the possible factors which may affect this method. METHODS: Gastric cancer cell line MGC-803 and intestinal cancer cell line HCT-116 were chosen. Cells were treated with different drugs, temperatures and duration. Cell viability and growth were measured by MTS-PMS assay. The morphology of the cells was observed under a microscope. RESULTS: Significant synergistic effect was observed when the two cancer cell lines were treated with 5-FU, MMC, DDP and THP in combination with elevated hyperthermia from 41 degrees C to 45 degrees C compared with control group (P<0.01). The strongest effect was achieved at 45 degrees C, which the inhibitory effects of these four drugs were 61.7%, 79.2%, 88.7%, 94.7% on MGC-803 and 76.4%, 78.7%, 77.8%, 91.7 on HCT-1116, respectively. The inhibitory effect demonstrated a time and dose-dependent manner in HCT-116 cells within a certain period of time. The effect revealed a flat curve after 90 min when HCT-116 was treated with 43 centigrade. THP had the strongest effect at any conditions among all tested drugs (P<0.01). Either simple thermotherapy or chemohyperthermia displayed considerable killing effects on cancer cells which were confirmed by microscope observation. And a great deal of dead cells were observed when treated with chemohyperthermia. CONCLUSIONS: DDP or MMC reveals relatively satisfactory antitumor effects with the optimal temperature of 43-45 degrees C. Taken practical application into consideration, 60 min may be selected in clinical use. Synergistic antitumor effects of THP in combination with hyperthermia were prior to 5-FU, DDP or MMC, which deserve further clinical research.


Assuntos
Neoplasias do Colo/patologia , Doxorrubicina/análogos & derivados , Hipertermia Induzida , Neoplasias Gástricas/patologia , Antibióticos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Neoplasias do Colo/terapia , Terapia Combinada , Doxorrubicina/farmacologia , Fluoruracila/farmacologia , Humanos , Mitomicina/farmacologia , Neoplasias Gástricas/terapia
15.
Zhonghua Wei Chang Wai Ke Za Zhi ; 9(4): 291-3, 2006 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-16886105

RESUMO

OBJECTIVE: To investigate the characteristics of metastasis and recurrence following curative resection for colonic carcinoma,and analyze the prognosis. METHODS: The clinicopathological and follow-up data of 310 patients with colon carcinoma undergoing curative resection were analyzed retrospectively. RESULTS: The recurrence rate after curative resection was 23.2% (72/310). The 5-year survival rate was 64.6%. Hepatic metastasis accounted for 38.9% of the cases. Gross classification,histological type, differentiation, lymph node metastasis were correlated with metastasis/recurrence. Univariate analysis revealed that gross classification, histological type, differentiation, lymph node metastasis, blood vessel invasion, TNM Stage, postoperative chemotherapy, portal chemotherapy were prognostic factors. Cox regression analysis revealed that only gross classification, lymph node metastasis, postoperative chemotherapy, portal chemotherapy were independent prognostic factors. CONCLUSIONS: Liver is the most common metastatic site after curative resection for colonic carcinoma. Gross classification, lymph node metastasis, postoperative chemotherapy, and portal chemotherapy are independent prognostic factors.


Assuntos
Neoplasias do Colo/patologia , Metástase Linfática/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos
16.
Ai Zheng ; 25(3): 264-8, 2006 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-16536976

RESUMO

BACKGROUND & OBJECTIVE: p55PIK is one of the regulatory subunits of phosphoinositide-3 kinase (PI3K). The unique 24 amino acids at N-terminal of p55PIK can bind Rb, and their ectopic expression may inhibit cell cycle progression. This study was to observe the effects of ectopic expression of the 24 amino acids at N-terminal of p55PIK (N24p55PIK) on cell proliferation and tumor growth of gastric cancer, and explore possible mechanism. METHODS: Plasmid pEGFPN24 was transfected into gastric cancer cell line MGC803 (MGC803/GFP-N24); pEGFPC1 was transfected into MGC803 cells as control (MGC803/pEGFPC1). Transient expression of GFP-N24 fusion protein was confirmed by Western blot. The growth of cell clones was determined by MTT assay. Effect of N24p55PIK overexpression on cell clonogenic ability was detected by colony formation assay. Tumorigenic capacity of MGC803/GFR-N24 cells was tested by tumorigenicity assay in nude mice. Influence of N24p55PIK on the expression of cell cycle protein Cyclin D1 was analyzed by Western blot. RESULTS: N24p55PIK was efficiently expressed in MGC803 cells, but the level of GFP-N24 fusion protein in MGC803/GFP-N24 cells was much lower than that of GFP in MGC803/pEGFPC1 cells. Compared with MGC803/pEGFPC1 cells, the growth of MGC803/GFP-N24 cells was suppressed and the cell doubling time was prolonged. The volume of MGC803/GFP-N24 cell colonies was smaller than that of MGC803/pEGFPC1 cell colonies. The tumorigenic capacity of MGC803 cells was decreased after transfection of pEGFPN24 in nude mice. The tumor weight and volume were (0.398+/-0.244) g and (408+/-268) mm(3) in MGC803/pEGFPN24 group, and were (0.763+/-0.193) g and (829+/-271) mm(3) in MGC803/pEGFPC1 group (P<0.05). The expression of Cyclin D1 was down-regulated in MGC803/GFP-N24 cells. CONCLUSIONS: Ectopic expression of N24p55PIK might inhibit tumor cell growth both in vitro and in vivo through decreasing the expression of Cyclin D1. The N24 peptide, derived from PI3K regulatory subunit p55PIK, may be a potential drug in antitumor treatment.


Assuntos
Adenocarcinoma Mucinoso/patologia , Proliferação de Células , Ciclina D1/metabolismo , Fosfatidilinositol 3-Quinases/biossíntese , Neoplasias Gástricas/patologia , Adenocarcinoma Mucinoso/metabolismo , Animais , Linhagem Celular Tumoral , Regulação para Baixo , Humanos , Camundongos , Camundongos Nus , Transplante de Neoplasias , Fosfatidilinositol 3-Quinases/genética , Plasmídeos , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Neoplasias Gástricas/metabolismo , Transfecção
17.
Zhonghua Zhong Liu Za Zhi ; 25(2): 175-7, 2003 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-12795848

RESUMO

OBJECTIVE: To evaluate the clinical and prognostic value of peritoneal lavage cytology (PLC) in detecting free cancer cells (FCC). METHODS: PLC of 66 gastric cancer patients being operated was prospectively analyzed to assess the prognostic significance of positive cytological finding and its relation with serosal invasion, lymph node metastasis and stage classification. RESULTS: The overall positive rate of cytology was 36.4% (24/66). These was a closely relation between positive cytology results and serosal invasion (P = 0.025), abdominal lymph node involvement (P < 0.005) and stage classification. Peritoneal recurrence in patients with positive cytological findings was significantly higher than that with negative results (P = 0.006 7). CONCLUSION: Micrometastasis to the abdominal cavity, formed by free cancer cells exfoliated from the tumor, are significantly responsible for peritoneal dissemination. Serosal invasion and metastatic nodes have greater risk for positive cytology and implies poor prognosis. Peritoneal lavage cytology, if practiced in all gastric cancer patients being operated, can predict the operative effect and prognosis, increase the accuracy of clinical stage and provide information for further adjuvant therapy.


Assuntos
Neoplasias Gástricas/patologia , Adulto , Idoso , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Irrigação Terapêutica
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