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1.
PLoS One ; 16(9): e0257019, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34473771

RESUMO

Nuclear factor kappa B (NF-κB) is a transcriptional factor that can be activated by radiotherapy and chemotherapy. The synthetic protease inhibitor nafamostat mesilate (NM) inhibits NF-κB activity and exerts antitumor actions in various types of cancer. In the present study, we hypothesized that NM might enhance the antitumor action of radiotherapy on gallbladder cancer (GBC) cells by inhibiting radiation-induced NF-κB activity. Thus, we investigated the correlation between radiotherapy and NF-κB activity in GBC cells. We assessed the in vitro effects of radiotherapy with or without NM on NF-κB activity, apoptosis of GBC cells (NOZ and OCUG-1), induction of apoptotic cascade, cell cycle progression, and viability of GBC cells using four treatment groups: 1) radiation (5 Gy) alone; 2) NM (80 µg/mL and 40 µg/mL, respectively) alone; 3) combination (radiation and NM); and 4) vehicle (control). The same experiments were performed in vivo using a xenograft GBC mouse model. In vitro, NM inhibited radiation-induced NF-κB activity. Combination treatment significantly attenuated cell viability and increased cell apoptosis and G2/M phase cell cycle arrest compared with those in the other groups for NOZ and OCUG-1 cells. Moreover, combination treatment upregulated the expression of apoptotic proteins compared with that after the other treatments. In vivo, NM improved the antitumor action of radiation and increased the population of Ki-67-positive cells. Overall, NM enhanced the antitumor action of radiotherapy on GBC cells by suppressing radiation-induced NF-κB activity. Thus, the combination of radiotherapy and NM may be useful for the treatment of locally advanced unresectable GBC.

2.
Anticancer Res ; 41(9): 4411-4416, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475062

RESUMO

BACKGROUND/AIM: Detection of hepatocellular carcinoma using intraoperative ultrasonography (IOUS) is indispensable for successful laparoscopic hepatectomy (LH). This study was performed to evaluate patients with intraoperatively unidentified tumours undergoing LH. PATIENTS AND METHODS: Seven patients who underwent LH for hepatocellular carcinoma and whose tumours were not detected using IOUS were included in this study. Clinical features, preoperative imaging, intraoperative imaging, surgical procedures, and pathological findings were evaluated. RESULTS: Using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging, all the tumours were enhanced in the arterial phase and rapidly washed out, becoming hypointense to the remainder of the liver. All tumours except one were <2 cm in size. Severe liver fibrosis was observed in all cases. Tumours that were invisible on preoperative ultrasonography also could not be detected using IOUS or indocyanine green fluorescence imaging. Five patients underwent hepatectomy based on anatomical landmarks and achieved curative resection, whereas curative resection failed in two patients. CONCLUSION: When tumours cannot be identified by IOUS, LH based on anatomical landmarks should be preferred. Importantly, invisible tumours on preoperative ultrasonography may not be identified intraoperatively during LH.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Cirrose Hepática/patologia , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Idoso , Carcinoma Hepatocelular/diagnóstico por imagem , Feminino , Gadolínio DTPA/administração & dosagem , Hepatectomia , Humanos , Verde de Indocianina/administração & dosagem , Laparoscopia , Cirrose Hepática/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Imagem por Ressonância Magnética Intervencionista , Masculino , Pessoa de Meia-Idade , Carga Tumoral , Ultrassonografia de Intervenção
3.
Cancer Sci ; 2021 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-34459070

RESUMO

Although the inhibition of acid ceramidase (AC) is known to induce antitumor effects in various cancers, there are few reports in pancreatic cancer, and the underlying mechanisms remain unclear. Moreover, there is currently no safe administration method of AC inhibitor. Here the effects of gene therapy using siRNA and shRNA for AC inhibition with its mechanisms for pancreatic cancer were investigated. The inhibition of AC by siRNA and shRNA using an adeno-associated virus 8 (AAV8) vector had antiproliferative effects by inducing apoptosis in pancreatic cancer cells and xenograft mouse model. Acid ceramidase inhibition elicits mitochondrial dysfunction, reactive oxygen species accumulation, and manganese superoxide dismutase suppression, resulting in apoptosis of pancreatic cancer cells accompanied by ceramide accumulation. These results elucidated the mechanisms underlying the antitumor effect of AC inhibition in pancreatic cancer cells and suggest the potential of the AAV8 vector to inhibit AC as a therapeutic strategy.

4.
Pancreas ; 50(3): 313-316, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33835961

RESUMO

OBJECTIVES: The aim of this study was to clarify the effectiveness of combination chemotherapy targeting gemcitabine (GEM)-induced nuclear factor kappa B as adjuvant therapy for pancreatic cancer. METHODS: Patients who were planned after curative surgery (residual tumor classification R0 or R1) for pancreatic cancer to receive six cycles of adjuvant chemotherapy of regional arterial infusion of nafamostat mesilate with GEM between June 2011 and April 2017 were enrolled in this single-center, institutional review board-approved phase II trial (UMIN000006163). The Kaplan-Meier method was used to estimate disease-free survival and overall survival. RESULTS: In 32 patients [male/female: 18/14; age: median, 65.5 years (range, 48-77 years); pathological stage (Union for International Cancer Control 8th): IA/IB/IIA/IIB/III, 2/2/9/18/1, respectively] who met the eligibility criteria, the median overall survival and disease-free survival were 36.4 months (95% confidence interval, 31.7-48.3) and 16.4 months (95% confidence interval, 14.3-22.0), respectively. Grade 4 treatment-related hematological toxicities were seen in 5 patients (15.6%) (all neutropenia). One patient developed grade 3 nonhematological toxicities (rash). CONCLUSIONS: Adjuvant chemotherapy with regional arterial infusion of nafamostat mesilate and GEM is safe and has potential as an option in adjuvant setting after curative surgery for pancreatic cancer.

5.
Breast Cancer ; 28(5): 1051-1061, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33840010

RESUMO

BACKGROUND: Oligometastatic breast cancer (OMBC) is characterized by limited metastatic tumor numbers and sites. We have reported a 20-year overall survival (OS) rate and relapse-free rate (RFR) of 34.1% and 27.4%, respectively, in a retrospective analysis of OMBC patients treated with curative intent including a multidisciplinary approach. Metastatic breast cancer (MBC) is generally incurable; however, OMBC might be a potentially curable subset. The previous analysis included isolated locoregional recurrence (ILRR) cases, which differs from distant metastasis in treatment strategies. Therefore, in this study, we excluded ILRR cases and provided an update on clinical outcomes. We also performed a detailed subgroup analysis of OMBC patients by introducing new prognostic variables. METHODS: Data of 73 OMBC patients, including 10 ILRR cases, treated in our institution between 1980 and 2010 were retrospectively analyzed. OMBC was defined as the presence of metastatic lesions in 1-2 organs, < 5 lesions per metastasized organ, and lesion diameter < 5 cm. RESULTS: The median follow-up duration was 151 (range 12-350) months. Twenty-eight (44%) patients received local therapy. Excluding ILRR cases, the OS rates were 28.3% and 18.9% and RFRs were 26.7% at 20 and 25 years, respectively. In multivariate analysis, single-organ involvement and three or fewer metastatic lesions per organ were associated with a longer progression-free and relapse-free interval (RFI). CONCLUSIONS: Relapse-free interval reached a plateau after 20 years at approximately 25% probability. Patients with long-term survival without disease relapse are considered cured. Curative-intent therapy should be considered for OMBC patients, especially those with low tumor volume.

6.
J Gastroenterol ; 56(3): 250-260, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33106918

RESUMO

BACKGROUND: Fibroblast growth factor receptor 2 (FGFR2) rearrangement is expected to be a novel therapeutic target in advanced/recurrent biliary tract cancer (BTC). However, efficient detection and the exact frequency of FGFR2 rearrangements among patients with advanced/recurrent BTC have not been determined, and the clinical characteristics of FGFR2 rearrangement-positive patients have not been fully elucidated. We aimed to determine the frequency of FGFR2 rearrangement-positive patients among those with advanced/recurrent BTC and elucidate their clinicopathological characteristics. METHODS: Paraffin-embedded tumor samples from formalin-fixed surgical or biopsy specimens of patients with advanced/recurrent BTC were analyzed for positivity of FGFR2 rearrangement by fluorescent in situ hybridization (FISH). RNA sequencing was performed on samples from all FISH-positive and part of FISH-negative patients. RESULTS: A total of 445 patients were enrolled. FISH was performed on 423 patients (272 patients with intrahepatic cholangiocarcinoma (ICC), 83 patients with perihilar cholangiocarcinoma (PCC), and 68 patients with other BTC). Twenty-one patients with ICC and four patients with PCC were diagnosed as FGFR2-FISH positive. Twenty-three of the 25 FISH-positive patients (20 ICC and 3 PCC) were recognized as FGFR2 rearrangement positive by targeted RNA sequencing. Younger age (≤ 65 years; p = 0.018) and HCV Ab- and/or HBs Ag-positivity (p = 0.037) were significantly associated with the presence of FGFR2 rearrangement (logistic regression). CONCLUSIONS: FGFR2 rearrangement was identified in ICC and PCC patients, and was associated with younger age and history of hepatitis viral infection.

8.
Int Cancer Conf J ; 9(2): 55-58, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32257754

RESUMO

A 48-year-old male was referred to our hospital for evaluation of motor speech disorders and difficulty in the movement of both the hands. The clinical diagnosis was Trousseau's syndrome due to advanced gallbladder cancer (cT3aN1M0). The patient received anticoagulation therapy and systemic chemotherapy (gemcitabine and cisplatin). Motor speech disorders and difficulty in movement of both hands were recovered. After 2 courses of chemotherapy, the primary tumor developed a massive hepatic invasion and the peripheral blood eosinophils increased gradually. The patient was admitted to our hospital for abdominal distension, fever, right upper quadrant pain, systemic edema, loss of appetite, and general malaise. The peripheral blood eosinophil count was markedly elevated to 45,900/µl (90.3%). The serum level of GM-CSF was high and there was no evidence of leukemia, allergic status and other diseases. The patient was diagnosed as paraneoplastic eosinophilia with advanced gallbladder cancer, which was suspected to produce GM-CSF. The patient received palliative support and died of disseminated intravascular coagulation 15 days after admission. We herein reported a fatal case of gallbladder cancer suspected of producing GM-CSF.

10.
Surgery ; 166(6): 991-996, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31353078

RESUMO

BACKGROUND: Liver metastasis is a common problem after pancreatectomy for pancreatic cancer. In pancreatic cancer cells, nuclear factor-κB is activated constitutively. Nuclear factor-κB activates matrix metalloproteinase-2/9, which plays an important role in cancer metastasis. Because the serine protease inhibitor FUT-175 suppresses nuclear factor-κB, we hypothesized that perioperative treatment with FUT-175 for pancreatic cancer may help to prevent liver metastasis. METHODS: We compared in vitro cell viability, cell invasiveness, nuclear factor-κB signaling, and the expression levels of matrix metalloproteinase signals between the control group (C group) and the FUT-175 group (F group) using the murine pancreatic cancer cells PAN02. In addition, we evaluated the in vivo effect of pretreatment with FUT-175 using an established model of liver metastasis in mice. Metastatic liver lesions were assessed with magnetic resonance imaging. Liver recurrence and overall survival were evaluated. Also, the antimetastatic effect of systemic administration of FUT-175 was examined. RESULTS: FUT-175 did not suppress the cell viability of PAN02 cells at or after 24 hours of treatment (P > .05); however, cell invasion was suppressed in the F group compared with the C group (P < .05). The levels of nuclear factor-κB activation, membrane type-1 (MT-1) matrix metalloproteinase (MMP)/matrix metalloproteinase-14 (MMP-14), and matrix metalloproteinase-2/9 (MMP-2/9) were lower in the F group compared with the C group. In vivo, both disease-free and overall survivals were prolonged in the F group compared with the C group. Systemic administration was also effective in suppressing the number of metastases. CONCLUSION: Perioperative treatment with FUT-175 may help to prevent early liver metastasis after pancreatectomy for pancreatic cancer.


Assuntos
Guanidinas/administração & dosagem , Neoplasias Hepáticas/prevenção & controle , NF-kappa B/antagonistas & inibidores , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Animais , Linhagem Celular Tumoral/transplante , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Intervalo Livre de Doença , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Injeções Intraperitoneais , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Masculino , Metaloproteinases da Matriz/metabolismo , Camundongos , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Assistência Perioperatória/métodos , Transdução de Sinais/efeitos dos fármacos
11.
Surg Case Rep ; 5(1): 103, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31236705

RESUMO

BACKGROUND: Metastatic biliary tract cancer (BTC) has poor prognosis. Recently, patients with metastatic BTC who respond well to systemic chemotherapy can be treated by radical resection or "conversion surgery." CASE PRESENTATION: A 67-year-old male patient was diagnosed with intrahepatic cholangiocarcinoma with para-aortic metastases [cT2N1M1, stage IVB]. He was enrolled in our phase II study for unresectable BTC consisting of cisplatin (25 mg/m2 i.v. for 30 min) followed by gemcitabine (1000 mg/m2 i.v. for 30 min) on days 1 and 8 and oral S-1 on alternate days. After 8 courses of this regimen, marked regression of para-aortic lymph metastases was achieved, and we performed extended left hepatic lobectomy with the caudate lobe, concomitant portal vein resection, and lymph node dissection including the para-aortic region. The patient made a satisfactory recovery and was discharged on postoperative day 25. Histopathological examination revealed more than 50% of the tumor area replaced with fibrosis, and curative resection was achieved (ypT2N1M1, stage IVB, Evans criteria IIb). The patient received adjuvant chemotherapy using S-1 for 12 months and remains well with no evidence of tumor recurrence as of 48 months after surgery. CONCLUSIONS: We herein report a successfully treated case of advanced BTC with para-aortic lymph node metastases by conversion surgery after combination chemotherapy using gemcitabine, cisplatin, and S-1.

13.
Pancreatology ; 19(1): 88-96, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30416041

RESUMO

BACKGROUND/OBJECTIVES: Pancreatic cancer consists of various subpopulations of cells, some of which have aggressive proliferative properties. The molecules responsible for the aggressive proliferation of pancreatic cancer may become molecular targets for the therapies against pancreatic cancer. METHODS: From a human pancreatic cancer cell line, MIA PaCa-2, MIA PaCa-2-A cells with an epithelial morphology and MIA PaCa-2-R cells with a non-epithelial morphology were clonogenically isolated by the limiting dilution method. Gene expression of these subpopulations was analyzed by DNA microarray. Gene knockdown was performed using siRNA. RESULTS: Although the MIA PaCa-2-A and MIA PaCa-2-R cells displayed the same DNA short tandem repeat (STR) pattern identical to that of the parental MIA PaCa-2 cells, the MIA PaCa-2-A cells were more proliferative than the MIA PaCa-2-R cells both in culture and in tumor xenografts generated in immunodeficient mice. Furthermore, the MIA PaCa-2-A cells were more resistant to gemcitabine than the MIA PaCa-2-R cells. DNA microarray analysis revealed a high expression of claudin (CLDN) 7 in the MIA PaCa-2-A cells, as opposed to a low expression in the MIA PaCa-2-R cells. The knockdown of CLDN7 in the MIA PaCa-2-A cells induced a marked inhibition of proliferation. The MIA PaCa-2-A cells in which CLDN7 was knocked down exhibited a decreased expression of phosphorylated extracellular signal-regulated kinase (p-Erk)1/2 and G1 cell cycle arrest. CONCLUSIONS: CLDN7 may be expressed in the rapidly proliferating and dominant cell population in human pancreatic cancer tissues and may be a novel molecular target for the treatment of pancreatic cancer.


Assuntos
Claudinas/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Proliferação de Células , Claudinas/genética , Pontos de Checagem da Fase G1 do Ciclo Celular , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Neoplasias Experimentais , Análise de Sequência com Séries de Oligonucleotídeos , RNA Interferente Pequeno
14.
Cancers (Basel) ; 10(10)2018 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-30336548

RESUMO

Neoadjuvant chemoradiotherapy followed by radical surgery is the standard treatment for patients with locally advanced low rectal cancer. However, several studies have reported that ionizing radiation (IR) activates nuclear factor kappa B (NF-κB) that causes radioresistance and induces matrix metalloproteinase (MMP)-2/-9, which promote tumor migration and invasion. Nafamostat mesilate (FUT175), a synthetic serine protease inhibitor, enhances the chemosensitivity to cytotoxic agents in digestive system cancer cells by inhibiting NF-κB activation. Therefore, we evaluated the combined effect of IR and FUT175 on cell proliferation, migration and invasion of colorectal cancer (CRC) cells. IR-induced upregulation of intranuclear NF-κB, FUT175 counteracted this effect. Moreover, the combination treatment suppressed cell viability and induced apoptosis. Similar effects were also observed in xenograft tumors. In addition, FUT175 prevented the migration and invasion of cancer cells caused by IR by downregulating the enzymatic activity of MMP-2/-9. In conclusion, FUT175 enhances the anti-tumor effect of radiotherapy through downregulation of NF-κB and reduces IR-induced tumor invasiveness by directly inhibiting MMP-2/-9 in CRC cells. Therefore, the use of FUT175 during radiotherapy might improve the efficacy of radiotherapy in patients with CRC.

15.
Ann Gastroenterol Surg ; 2(1): 65-71, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29863120

RESUMO

Pancreatic cancer is often resistant to chemotherapy. We previously showed the efficacy of combination treatment using gemcitabine and nafamostat mesilate (FUT-175) for patients with unresectable pancreatic cancer. However, the mechanisms that affect the sensitivity of FUT-175 are not fully understood. The purpose of the present study was to clarify the mechanism of the sensitivity to FUT-175, with a focus on the activity of glycogen synthase kinase-3ß (GSK-3ß). In vitro, we assessed sensitivity to FUT-175 in human pancreatic cancer cell lines (PANC-1 and MIAPaCa-2) and difference of signaling in these cells by cell proliferation assay, Western blot analysis and microarray. Next, we assessed cell viability, apoptotic signal and nuclear factor-kappa B (NF-κB) activity in response to treatment with FUT-175 alone and in combination with GSK-3 inhibitor or protein phosphatase 2A (PP2A) by cell proliferation assay, Western blot analysis and enzyme-linked immunosorbent assay. Phosphorylated GSK-3ß level was significantly higher in MIAPaCa-2 (high sensitivity cell) than in PANC-1 (low sensitivity cell). Cell viability and NF-κB activity were significantly decreased by addition of GSK-3 inhibitor to FUT-175, and levels of cleaved caspase-8 were increased by inhibition of GSK-3. PP2A inhibitor increased the levels of phosphorylated GSK-3ß and sensitized both cell lines to FUT-175 as measured by cell viability and apoptotic signal. The results indicate that GSK-3ß activity plays a key role in the antitumor effect of FUT-175 in pancreatic cancer cells, and regulation of GSK-3ß by PP2A inhibition could be a novel therapeutic approach for pancreatic cancer.

16.
Oncotarget ; 9(20): 15292-15301, 2018 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-29632644

RESUMO

Introduction: Nuclear factor κB (NF-κB) plays an important role in cancer progression and causes therapeutic resistance to chemotherapy. Pomalidomide, a third-generation immunomodulating drug derived from thalidomide, has been approved for uncontrolled multiple myeloma. We hypothesized that pomalidomide may inhibit the anticancer agent-induced NF-κB activity and enhance chemosensitization of combination chemotherapy with gemcitabine and S1 (Gem/S1) in pancreatic cancer. Methods: In vitro, we assessed NF-κB activity, induction of caspase cascade, cell apoptosis and cell proliferation using human pancreatic cancer cell lines (MIA PaCa-2 and PANC-1). In vivo, we established an orthotopic xenograft mouse model for human pancreatic cancer by injection of PANC-1 cells. At 5 weeks after injection, the animals were randomly divided into four groups and treated with Gem (100 mg/kg) /S1 (10 mg/kg), with oral administration of pomalidomide (0.5 mg/kg), with combination of gemcitabine, S1, and pomalidomide or vehicle only. Results: Although chemotherapeutic agents induced NF-κB activation in pancreatic cancer cells, pomalidomide inhibited anticancer agent-induced NF-κB activation (p < 0.01). Of the four groups tested for the apoptosis-related caspase signals and apoptosis under both in vitro and in vivo conditions, Gem/S1/Pomalidomide group demonstrated the strongest activation of the caspase signals and proapoptotic effect. In Gem/S1/Pomalidomide group, cell proliferation and tumor growth were slower than those in other groups both in vitro and in vivo (p < 0.01). There were no obvious adverse effects except for thrombocytosis by using pomalidomide. Conclusions: Pomalidomide promotes chemosensitization of pancreatic cancer by inhibiting chemotherapeutic agents-induced NF-κB activation.

17.
Oncotarget ; 9(21): 15780-15791, 2018 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-29644009

RESUMO

Background: Chemotherapy with gemcitabine and nab-paclitaxel (gemcitabine/nab-paclitaxel) is recommended for unresectable pancreatic cancer. However, the therapeutic efficacy is attenuated by the antitumor agent-induced activation of nuclear factor-κB (NF-κB). Thalidomide inhibits NF-κB activation, therefore, we hypothesized that pomalidomide, a third-generation IMiD, would also inhibit NF-κB activation and enhance the antitumor effects of gemcitabine/nab-paclitaxel. Methods: In vitro, we assessed NF-κB activity and apoptosis in response to pomalidomide alone, gemcitabine/nab-paclitaxel, or combination of pomalidomide and gemcitabine/nab-paclitaxel in human pancreatic cancer cell lines (PANC-1 and MIA PaCa-2). In vivo, we established orthotopic model and the animals were treated with oral pomalidomide and injection of gemcitabine/nab-paclitaxel. Results: In pomalidomide and gemcitabine/nab-paclitaxel group, gemcitabine/nab-paclitaxel-induced NF-κB activation was inhibited and apoptosis was enhanced in comparison with those in the other groups both in vitro and in vivo. Especially, this study revealed for the first time that pomalidomide enhances p53 on pancreatic cancer cells. The tumor growth in the pomalidomide and gemcitabine/nab-paclitaxel group was significantly slower than that in the gemcitabine/nab-paclitaxel group. Moreover, pomalidomide induced G0/G1 cell cycle arrest and suppressed angiogenesis. Conclusions: Pomalidomide enhanced the antitumor effect of gemcitabine/nab-paclitaxel by inhibition of NF-κB activation. This combination regimen would be a novel strategy for treating pancreatic cancer.

18.
Anticancer Res ; 38(4): 2369-2375, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29599363

RESUMO

BACKGROUND/AIM: Omega-3 fatty acids may improve cancer cachexia, but only in patients with pancreatic and bile duct cancer. Patients with pancreatic cancer commonly suffer from exocrine pancreatic insufficiency, and the ingestion of digestive enzyme supplements may improve absorption. PATIENTS AND METHODS: Racol®, an enteral nutrient formulated with omega-3 fatty acids, was administered to patients with unresectable pancreatic and bile duct cancer. The skeletal muscle mass and blood test data were taken pre-administration and at 4 and 8 weeks after. Patients with pancreatic cancer were given the digestive enzyme supplement LipaCreon® from the fifth week after the start of administration. RESULTS: In all 27 patients, skeletal muscle mass was significantly increased at both 4 and 8 weeks after the start of administration versus pre-administration (p=0.006, p=0.002, respectively). CONCLUSION: Omega-3 fatty acid supplementation in patients with unresectable pancreatic and bile duct cancer may improve cancer cachexia.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias dos Ductos Biliares/dietoterapia , Neoplasias dos Ductos Biliares/tratamento farmacológico , Ácidos Graxos Ômega-3/administração & dosagem , Neoplasias Pancreáticas/dietoterapia , Neoplasias Pancreáticas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Albuminas/administração & dosagem , Neoplasias dos Ductos Biliares/patologia , Caquexia/prevenção & controle , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Suplementos Nutricionais , Combinação de Medicamentos , Ácidos Graxos Ômega-3/farmacologia , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Apoio Nutricional/métodos , Compostos Organoplatínicos/uso terapêutico , Ácido Oxônico/uso terapêutico , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/patologia , Piridinas/uso terapêutico , Tegafur/uso terapêutico
19.
Anticancer Res ; 38(2): 987-992, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29374731

RESUMO

BACKGROUND: The purpose of this study was to evaluate the prognostic index of the preoperative platelet to albumin ratio (PAR) in patients who underwent primary resection for cholangiocarcinoma. PATIENTS AND METHODS: A total of 59 patients were divided into two groups: those with PAR ≥72.6×103 or <72.6×103 according to the area under the receiver operating characteristics curve. RESULTS: PAR was significantly inversely associated with overall (OS) and disease-free (DFS) survival on univariate analysis. PAR showed significance on multivariate analysis for OS (hazard ratio=6.232, 95% confidence interval=1.283-30.279, p=0.023), along with tumor differentiation (p=0.009), nodal involvement (p=0.001), intraoperative blood loss (p=0.001), and serum carcinoembryonic antigen (CEA) (p=0.012). High PAR was also significantly associated poor DFS on multivariate analysis (hazard ratio(HR)=4.422, 95% confidence interval(CI)=1.168-16.732, p=0.029), along with tumor differentiation (p=0.009). CONCLUSION: PAR is a useful prognostic index for OS and DFS in patients with cholangiocarcinoma after primary resection. By accumulating cases prospectively, this new index may be a reference for use before neoadjuvant chemotherapy.


Assuntos
Albuminas/metabolismo , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Plaquetas/patologia , Colangiocarcinoma/patologia , Hepatectomia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/cirurgia , Biomarcadores Tumorais/análise , Colangiocarcinoma/metabolismo , Colangiocarcinoma/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
20.
J Infect Chemother ; 24(4): 298-301, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29174919

RESUMO

Although, gastric cancer is one of the most common cancers worldwide, alpha-fetoprotein (AFP) producing human epidermal growth factor receptor 2 (HER2) positive gastric cancers are rare. AFP producing gastric cancer has a poor prognosis and an appropriate treatment option has not been established to date. A 75-year-old woman with AFP- producing gastric cancer was treated with S-1, an oral fluoropyrimidine derivative, chemotherapy after distal gastrectomy. Recurrence of gastric cancer was observed after 18 months and immunohistochemistry analysis showed AFP and HER2 positive gastric cancer. The patient received combination therapy containing capecitabine, cisplatin, and trastuzumab. Computed tomography scans showed regression of the lymph node metastasis. The patient's quality of life substantially improved after the treatment. Thus, the present case suggests that AFP and HER2 positive gastric cancer can be effectively treated with, capecitabine, cisplatin, and trastuzumab combination therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/tratamento farmacológico , alfa-Fetoproteínas/metabolismo , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Capecitabina/uso terapêutico , Cisplatino/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Metástase Linfática/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Ácido Oxônico/uso terapêutico , Qualidade de Vida , Neoplasias Gástricas/metabolismo , Tegafur/uso terapêutico , Trastuzumab/uso terapêutico , Resultado do Tratamento
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