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1.
Anticancer Res ; 39(10): 5565-5572, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570451

RESUMO

BACKGROUND/AIM: The aim of the study was to evaluate the status of extravasated platelet activation (EPA) surrounding podoplanin (PDPN)-positive cancer-associated fibroblasts (CAFs) in pancreatic cancer stroma by neoadjuvant chemotherapy. PATIENTS AND METHODS: A total of 74 patients were enrolled in this study. We investigated CD42b and PDPN expression in the groups of untreated, gemcitabine (GEM) alone, GEM plus S-1 (GS) and GEM plus nab-paclitaxel (GnP). RESULTS: CD42b expression in surrounding CAFs was observed in 58% patients. CD42b expression was significantly correlated with PDPN expression. CD42b-positive cases were significantly lower in the group treated with GnP than in the untreated group and groups treated with GEM alone or GS. PDPN expression was reduced in the GnP group, as revealed by markedly disorganized collagen and a low density of PDPN-positive fibroblasts. There was a significantly lower CD42b expression and fewer PDPN-positive fibroblasts in the GnP group than in untreated, GEM alone, and GS groups, but there was no significant difference between the latter three groups. CONCLUSION: There is a significant association between EPA and PDPN-positive CAFs in pancreatic cancer stroma. Our data suggest that the GnP regimen decreases EPA through PDPN-positive CAF depletion.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fibroblastos Associados a Câncer/efeitos dos fármacos , Glicoproteínas de Membrana/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Ativação Plaquetária/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminas/uso terapêutico , Fibroblastos Associados a Câncer/metabolismo , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Ácido Oxônico/uso terapêutico , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/metabolismo , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Tegafur/uso terapêutico
2.
Anticancer Res ; 39(10): 5339-5344, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570427

RESUMO

BACKGROUND/AIM: Gemcitabine is standard first-line treatment for patients with advanced pancreatic cancer, however the efficacy is limited. Although acquired drug resistance and side-effects are known to limit efficacy, opposite effects of a drug, which enhance the malignancy of treated cancer, have been observed but are not well understood. The aim of the present study was to determine whether gemcitabine has such opposite effects on the BxPC-3 human pancreatic cancer cell line expressing green fluorescent protein (BxPC-3-GFP) in an orthotopic mouse model. MATERIALS AND METHODS: BxPC-3-GFP tumors grown subcutaneously in nude mice were harvested. Tumor fragments were orthotopically implanted in the tail of the pancreas of nude mice using the technique of surgical orthotopic implantation. The BxPC-3-GFP orthotopic models were divided randomly into three groups: Group 1: untreated control; Group 2: low-dose gemcitabine (weekly intraperitoneal injection at 25 mg/kg for 6 weeks); Group 3: high-dose gemcitabine (weekly intraperitoneal injection at 125 mg/kg for 6 weeks). Each group comprised eight mice. Tumor size, fluorescent area of metastases, and body weight were measured. RESULTS: Low- and high-dose gemcitabine inhibited primary tumor growth in a dose-dependent manner, and to the greatest extent by high-dose gemcitabine compared to the untreated control (p=0.0134). In contrast, the extent of metastasis on the peritoneum was significantly increased by low-dose gemcitabine compared to the untreated control (p=0.0112). The extent of metastasis showed no significant difference between the untreated control and mice treated with high-dose gemcitabine. Body weight of the treated mice was not significantly different from that of the untreated mice. CONCLUSION: The use of very bright GFP expressing of BxPC-3 cells and the orthotopic model demonstrated an unexpected increase in metastasis by low-dose gemcitabine. Future experiments will investigate the mechanism of this phenomenon.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Desoxicitidina/análogos & derivados , Metástase Neoplásica/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desoxicitidina/administração & dosagem , Modelos Animais de Doenças , Proteínas de Fluorescência Verde/metabolismo , Humanos , Camundongos , Camundongos Nus , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Neoplasias Pancreáticas/metabolismo
3.
Anticancer Res ; 39(10): 5369-5374, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570431

RESUMO

BACKGROUND/AIM: Cytokine-induced killer (CIK) cells are ex vivo expanded major histocompatibility complex (MHC)-unrestricted cytotoxic cells with promising effects against a variety of cancer types. Regulatory T-cells (T-reg) have been shown to reduce the effectiveness of CIK cells against tumor cells. Peptide P60 has been shown to inhibit the immunosuppressive functions of T-regs. This study aimed at examining the effect of p60 on CIK cells efficacy against renal and pancreatic cancer cells. MATERIALS AND METHODS: The effect of P60 on CIK cytotoxicity was examined using flow cytometry, WST-8-based cell viability assay and interferon γ (IFNγ) ELISA. RESULTS: P60 treatment resulted in a significant decrease in the viability of renal and pancreatic cancer cell lines co-cultured with CIK cells. No increase in IFNγ secretion from CIK cells was detected following treatment with P60. P60 caused no changes in the distribution of major effector cell populations in CIK cell cultures. CONCLUSION: P60 may potentiate CIK cell cytotoxicity against tumor cells.


Assuntos
Células Matadoras Induzidas por Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Fatores de Transcrição Forkhead/antagonistas & inibidores , Neoplasias Renais/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Peptídeos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura/métodos , Células Matadoras Induzidas por Citocinas/metabolismo , Citotoxicidade Imunológica/efeitos dos fármacos , Humanos , Interferon gama/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Neoplasias Renais/metabolismo , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Neoplasias Pancreáticas/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo
4.
Anticancer Res ; 39(10): 5781-5787, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570482

RESUMO

BACKGROUND: Neoadjuvant chemotherapy (NAC) is established in the treatment of ductal pancreatic adenocarcinoma for downsizing borderline-resectable pancreatic cancer (BRPC) and may affect nodal positivity and rates of R0 resection. This study aimed to identify the impact of NAC on postoperative histopathological parameters with a prognostic relevance. PATIENTS AND METHODS: A one-to-three matched-pair analysis, including an overall total of 132 patients (25% treated with NAC and subsequent resection and 75% undergoing upfront surgery) was performed. Influence of NAC on nodal positivity, lymphatic, vascular and perineural invasion, as well as resection stage and grading, was examined. Furthermore, perioperative complications, in-hospital stay, re-admission rates, mortality, as well as preoperative body mass index and American Association of Anesthesiologist classification scores, were evaluated. RESULTS: Patients treated with NAC significantly less frequently had lymphatic tissue invasion (lymph node invasion: 51.5% vs. 72.7%; p=0.032, and lymphatic vessel invasion 9.4% vs. 55.3%; p=0.0004), whereas vascular and perineural invasion, as well as grading and resection state were not significantly different. Carbohydrate antigen 19-9 regression in correlation with nodal positivity also did not differ, and both groups showed comparable perioperative complication rates. Occurrence and severity of postoperative pancreatic fistula (18.2% vs. 24.3%; p=0.034) were significantly lower in patients who had undergone NAC. CONCLUSION: NAC significantly affects postoperative histopathological tumour stage in BRPC and appears to be a safe treatment option without increased perioperative complications, re-admission, in-hospital stay, or mortality. Further studies are mandatory to underline the suitability of NAC for ductal pancreatic adenocarcinoma subgroups in order to guide clinicians in their daily decision-making comprehensively.


Assuntos
Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno CA-19-9/metabolismo , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/terapia , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias/métodos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/terapia , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos
5.
Anticancer Res ; 39(10): 5821-5830, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570487

RESUMO

BACKGROUND/AIM: The significance of the anatomical variations of proximal jejunal vein [the so-called 1st jejunal vein (J1v)] has been reported from a technical standpoint. The aim of this study was to retrospectively investigate the prognostic impact of the anatomical variations of J1v in the surgical treatment of resectable pancreatic cancer (PC). PATIENTS AND METHODS: A total of 49 patients with resectable PC located in the uncinate process were included in this study. The J1v converging pattern was divided into 2 groups in terms of its relation to the SMA (i.e., the J1v status): i) group D: the J1v travels posterior to the SMA; ii) group V: the J1v travels anterior to the SMA. The associations between the J1v status and surgical outcome were assessed. RESULTS: The 5-year survival rate after resection in group V (35%) was significantly lower than that in group D (70%) (p=0.029), and the J1v status of group V was the only independent negative prognostic factor (HR=5.49; 95% CI=1.69-19.3; p=0.005). CONCLUSION: The J1v converging pattern is a significant prognostic variable in patients with PC located in the uncinate process: the J1v status of group V was significantly associated with impaired survival.


Assuntos
Jejuno/patologia , Neoplasias Pancreáticas/patologia , Veia Porta/patologia , Idoso , Quimiorradioterapia/métodos , Feminino , Humanos , Jejuno/efeitos dos fármacos , Jejuno/efeitos da radiação , Masculino , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias/métodos , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Pâncreas/efeitos da radiação , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/radioterapia , Veia Porta/efeitos dos fármacos , Veia Porta/efeitos da radiação , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
6.
Medicine (Baltimore) ; 98(40): e17443, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577767

RESUMO

RATIONALE: Pancreatic cancer (PC) is considered as one of the deadliest cancers all over the world. Germline and somatic BRCA1/2 mutations have been widely studied in breast and ovarian carcinomas as they have been found to enhance the risk for disease progression. Olaparib, an oral poly(adenosine diphosphate-ribose)polymerase (PARP) inhibitor, has been approved for the treatment strategy of ovarian cancer with any BRCA1/2 mutations. There is a lack of studies which focus on the treatment of other cancer with BRCA-Mutation. PATIENT CONCERNS: This report describes a patient whose presenting complaints were "Physical examination showed that the pancreas was occupied for one month." He initially was diagnosed with stage IV PC based on conventional imaging and pathologic assessment. He had a known germline BRCA 2 mutation, which exhibited a good response to PARP inhibitor therapy. DIAGNOSIS: Through the biopsy histopathological examination, imaging examination, and genetic testing, the patient was diagnosed as metastatic PC with BRCA2 mutation. INTERVENTIONS: He received gemcitabine and albumin-bound paclitaxel chemotherapy from March 15, 2017 to June 30, 2017, and Nivolumab immunotherapy as the maintenance therapy. After serum CA-199 level increased, Olaparib was orally administered from August 17, 2017 to March. After tumor relapsed, he received multiple lines of chemotherapy, including Trametinib Oxaliplatin, S-1, bevacizumab, and irinotecan liposome injection till July 17, 2018. OUTCOMES: We observed the patient had a good progression-free survival (7.4 months); the lesion of the pancreas was classified as partial disease through Olaparib treatment, which indicated significant shrinkage. But it is difficult to conclude whether such therapy could help prolong the overall survival for such patients. LESSONS: The targeted therapy Olaparib showed early signs of potential in treating PC in patients with mutations of the BRCA genes. With emerging therapeutic modalities and next-generation sequencing development, it is increasingly relevant to consider mutation screenings of patients with PC.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Genes BRCA2 , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Adenocarcinoma/genética , Adenocarcinoma/secundário , Idoso , Mutação em Linhagem Germinativa/genética , Humanos , Masculino , Neoplasias Pancreáticas/genética
8.
Gan To Kagaku Ryoho ; 46(9): 1453-1455, 2019 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-31530789

RESUMO

An 80-year-old woman was diagnosed with pancreatic head cancer, and pancreaticoduodenectomy was performed. Twelve months after the operation, chest CT scans showed the presence ofmultiple nodules in both the lungs. Because ofthe potential negative side effects of anti-cancer drugs, the patient underwent chemotherapy with dose-down biweekly adminis- tration ofgemcitabine (1,000mg/day/body≒750mg/m2. Chest CT examination every 2-3 months revealed no rapid increase in multiple tumors. Nineteen months after starting gemcitabine therapy, there was an elevation in tumor marker and a gradual increase in lung metastases. We performed combination chemotherapy with nab-paclitaxel. However, owing to side effects, only 2 courses of nab-paclitaxel were administered, and the therapy was switched to only gemcitabine administration. Later, respiratory distress accompanied by pleural effusion developed, and the patient died of the original disease 27 months after recurrence. Here, we report a case ofan elderly patient with multiple lung metastases ofpancreatic cancer in whom lung metastases were controlled by biweekly dose-down administration of gemcitabine.


Assuntos
Desoxicitidina/análogos & derivados , Neoplasias Pulmonares , Neoplasias Pancreáticas , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia , Paclitaxel , Neoplasias Pancreáticas/tratamento farmacológico
9.
Zhonghua Wai Ke Za Zhi ; 57(9): 691-697, 2019 Sep 01.
Artigo em Chinês | MEDLINE | ID: mdl-31474062

RESUMO

Objectives: To examine the expression of the long coding RNA GSTM3TV2 in pancreatic cancer tissues and to examine its role and mechanism in chemoresistance of pancreatic cancer cells. Methods: The expression of lncRNA GSTM3TV2 in 15 pancreatic cancer specimens and corresponding adjacent to cancer tissue samples diagnosed by Department of Pathology, Peking Union Medical College Hospital was detected by real-time PCR.And the expressions of GSTM3TV2 in pancreatic cancer cell AsPC-1, BxPC-3, MIAPaCa-2, PanC-1, SU86.86, T3M4, and chemoresistant cells AsPC-1/GR and MIAPaCa-2/GR, and human pancreatic nestin-expressing cells hTERT-HPNE were detected. Pancreatic cancer cell lines were transfected with GSTM3TV2-pcDNA3.1(+)in order to get cells with GSTM3TV2 overexpression.GSTM3TV2-siRNA was transfected into pancreatic cancer cells to knock down GSTM3TV2. The cell chemoresistance was measured by CCK-8 and flow cytometry assay when incubated with nab-paclitaxel. At the same time, subcutaneous xenograft tumor models were established in nude mice to observe the effect of GSTM3TV2 on chemoresistance of tumor growth in nude mice.Western blot assay was also performed to detect the molecular mechanism of chemoresistance of GSTM3TV2. Results: Comparing toadjacent tissues(0.084±0.019), GSTM3TV2 expression was significantly upregulated in the pancreatic cancer tissues(0.493±0.084) (t=5.146, P<0.05). GSTM3TV2 expression were higher in the chemotherapy resistance pancreatic cancer cells AsPC-1/GR(210.799±19.788) and MIAPaCa-2/GR(122.408±23.419) than that in the AsPC-1(3.793±0.615) and the MIAPaCa-2(5.179±1.095)(t=21.800,P<0.05;t=-18.490,P<0.05). The results of in vivo experiments showed that the volume of subcutaneously transplanted tumors in the overexpressing GSTM3TV2 group ((1 059.609±102.498)mm(3)) was significantly larger than that in the control group((566.414±81.087) mm(3)) by treated with nab-paclitaxel(t=4.230,P<0.05).Meanwhile, GSTM3TV2 could promote the expression of Cyclin D1, CDK6, Cyclin E1, Vimentin, N-cadherin, ZEB1, Snail and Slug; but decrease cleaved caspase-3, cleaved PARP in pancreatic cancer cells. Conclusions: The expression level of GSTM3TV2 in pancreatic canceris higher than that in paired adjacent tissues. GSTM3TV2 may act as an oncogene to promote chemoresistance in pancreatic cancer through regulation of cell proliferation, apoptosis, and epithelial-mesenchymal transition.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Glutationa Transferase/genética , Oncogenes/genética , Neoplasias Pancreáticas/genética , RNA não Traduzido/genética , Animais , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/genética , Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Nus , Neoplasias Pancreáticas/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto
10.
J Cancer Res Clin Oncol ; 145(11): 2855-2862, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31506738

RESUMO

PURPOSE: The treatment of pancreatic carcinoma remains a challenge as prognosis is poor, even if confined to a single anatomical region. A regional treatment of pancreatic cancer with high drug concentrations at the tumor site may increase response behaviour. Intra-arterial administration of drugs generates homogenous drug distribution throughout the entire tumor volume. METHODS: We report on treatment outcome of 454 patients with advanced pancreatic carcinoma (WHO stage III: 174 patients, WHO stage IV: 280 patients). Patients have been separated to two different treatment protocols. The first group (n = 233 patients) has been treated via angiographically placed celiac axis catheters. The second group (n = 221 patients) had upper abdominal perfusion (UAP) with stopflow balloon catheters in aorta and vena cava. Both groups have been treated with a combination of cisplatin, adriamycin and mitomycin. RESULTS: For stage III pancreatic cancer, median survival rates of 8 and 12 months were reached with IA and UAP treatment, respectively. For stage IV pancreatic cancer, median survival rates of 7 and 8.5 months were reached with IA and UAP treatment, respectively. Resolution of ascites has been reached in all cases by UAP treatment. Toxicity was generally mild, WHO grade I or II, toxicity grade III or IV was only noted in patients with severe systemic pretreatment. The techniques, survival data and detailed results are demonstrated. CONCLUSIONS: Responsiveness of pancreatic cancer to regional chemotherapy is drug exposure dependent. The isolated perfusion procedure is superior to intra-arterial infusion in survival times.


Assuntos
Abdome/irrigação sanguínea , Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Infusões Intra-Arteriais/mortalidade , Neoplasias Pancreáticas/mortalidade , Abdome/cirurgia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
11.
Cancer Treat Rev ; 80: 101895, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31542591

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Recent studies have shown that 4-20% of patients with PDAC have a germline BReast CAncer (gBRCA) genes 1 and 2 mutation (m). Because homologous recombination is impaired in patients with gBRCAm, some reports suggested that these tumors may be more sensitive to platinum compounds. Therefore, this systematic review and meta-analysis focused on benefit of patients with gBRCAm receiving a platinum-based chemotherapy (PtCh) compared with those treated with a non-platinum-based chemotherapy (NPtCh). MATERIAL AND METHODS: The following electronic databases were searched from inception to May 12, 2018: PubMed (MEDLINE), EMBASE, and Cochrane Library. Abstracts from conferences were also reviewed for inclusion. Cohort, case-control and randomized studies of patients with PDAC and gBRCAm were eligible for inclusion if they provided data to compare patients receiving PtCh vs NPtCh. The primary endpoint was overall survival (OS) in the PtCh group vs the NPtCh group in patients with clinical stage III (locally advanced) or IV (metastatic) (CS III-IV) PDAC. RESULTS: Of 112 studies identified, 6 were included (total of 108 patients); of these, 4 provided sufficient data for meta-analysis. Half of the patients were males, with a mean age ranging from 58 to 63 years. The OS in the 85 patients with CS III-IV PDAC was higher in the PtCh group (23.7 vs 12.2 months; mean difference of 10.21 months, 95% confidence interval [CI] 5.05-15.37; P < 0.001; very low quality of evidence). PtCh was associated with a lower mortality (62.3 vs 87.5%; relative risk of 0.80, 95%CI 0.66-0.97; P = 0.021; very low quality of evidence). CONCLUSION: Our study confirmed the hypothesis that patients with CS III-IV gBRCAm preferably benefit from a PtCh compared with NPtCh. However the very low quality of evidence should induce to be careful about the risk of potential biases. The generated hypothesis should be prospectively investigated in homogenous clinical settings.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Genes BRCA1 , Genes BRCA2 , Mutação em Linhagem Germinativa , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Humanos , Compostos Organoplatínicos/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Gan To Kagaku Ryoho ; 46(8): 1259-1263, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31501367

RESUMO

We retrospectively analyzed adverse effects(AEs), overall survival(OS), and progression-free survival(PFS)in 15 consecutive patients treated with FOLFIRINOX as the first-line treatment for recurrent or unresectable pancreatic ductal adenocarcinoma( PDAC)between February 2014 and December 2017 in our hospital. Eleven patients were treated for unresectable PDAC with distant metastases(UR-M), and 4 were treated for locally advanced unresectable PDAC(UR-LA). The median age was 56(range: 40-75)years. Nine patients were male, and 6 were female. The performance status was 0 or 1 in all patients. Tumors were located in the pancreas head in 8 cases and in the body-tail in 7 cases. Grade 5 AEs were observed in 1 case in which liver abscess causing sepsis resulted in mortality. The response rate was 20.0%, and the disease control rate was 66.7%. Two patients underwent conversion surgery after FOLFIRINOX treatment. Seven patients received a nab-paclitaxel plus gemcitabine regimen as second-line treatment. The median OS and PFS were 17.0 and 8.4 months, respectively, and the 1-year survival rate was 66.7%. FOLFIRINOX for recurrent and unresectable PDAC showed relatively good tumor control. However, strict attention is required for severe AEs. Conversion surgery might be effective in patients who are good responders even if they have metastatic disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas , Adulto , Idoso , Carcinoma Ductal Pancreático , Feminino , Fluoruracila , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/tratamento farmacológico , Estudos Retrospectivos
15.
J Surg Oncol ; 120(6): 976-984, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31452208

RESUMO

BACKGROUND AND OBJECTIVES: Conclusive evidence in favor of neoadjuvant therapy for those with non-metastatic pancreatic ductal adenocarcinoma (PDAC) is still lacking. The objective of this study was to evaluate the survival benefit of neoadjuvant therapy vs upfront surgery for patients with non-metastatic PDAC. METHODS: The study involved 565 patients undergoing neoadjuvant therapy or upfront surgery as the primary treatment for PDAC. Propensity score matching was performed between the neoadjuvant therapy group (NAT group) and the upfront surgery group (UFS group) using 20 clinical variables at diagnosis. Overall survival and surgical pathology were compared between the two treatment groups on an intent-to-treat basis. RESULTS: In the matched cohort, the NAT group (n = 91) had a longer median overall survival than the UFS group (n = 91) (23.1 months vs 18.5 months, P = .043). The rate of patients undergoing surgical resection was lower in the NAT group (58% vs 80%, P = .001). Regarding surgical pathology, the NAT group had smaller tumor size (2.8 cm vs 4.0 cm, P = .001), lower incidence of positive surgical margins (8% vs 30%, P < .002), and less lymph node metastasis (45% vs 78%, P < .001). CONCLUSIONS: The strategy of neoadjuvant therapy before surgical resection appears to offer pathologic effect and survival benefit for the patients presenting with non-metastatic PDAC.


Assuntos
Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/mortalidade , Análise de Intenção de Tratamento , Terapia Neoadjuvante/mortalidade , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/mortalidade , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Quimioterapia Adjuvante , Estudos de Coortes , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Pontuação de Propensão , Taxa de Sobrevida , Adulto Jovem
16.
Life Sci ; 233: 116732, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31394125

RESUMO

AIMS: Linderane, an important bioactive compound in Linderae, improved glucose and lipid metabolism in ob/ob mice. However, the effect of linderane on streptozotocin (STZ)-induced oxidative damage in INS-1 cells remains unclear. MAIN METHODS: INS-1 cells were pre-treated with different doses of linderane for 2 h and then treated with 3 mM STZ for 12 h. Cell viability was determined by MTT assay. Cell apoptosis was detected using an Annexin V-FITC Apoptosis Detection Kit. The level of intracellular ROS was determined using dichlorofluorescein-diacetate (DCFH-DA). The activities of insulin secretion, SOD, catalase (CAT) and GPx were measured using ELISA kits. The expression levels of bax, bcl-2, p38, p-p38, nuclear Nrf2 and HO-1 were measured using western blot. KEY FINDINGS: The results showed that STZ-caused inhibitory effects on cell viability and insulin secretion were mitigated by linderane. Furthermore, linderane inhibited apoptosis and oxidative stress in STZ-induced INS-1 cells. Finally, linderane suppressed the activation of p38 MAPK pathway, as well as enhanced the activation of Nrf2 pathway in STZ-induced INS-1 cells. Activation of p38 MAPK pathway or inhibition of Nrf2 significantly reversed the protective effects of linderane against STZ-induced ROS production and cell apoptosis. SIGNIFICANCE: The protective effects of linderane on STZ-induced INS-1 cells might be attributed to the inhibition of p38 MAPK and activation of Nrf2 pathway.


Assuntos
Apoptose/efeitos dos fármacos , Furanos/farmacologia , Insulina/metabolismo , Insulinoma/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Sesquiterpenos/farmacologia , Estreptozocina/toxicidade , Animais , Insulinoma/metabolismo , Insulinoma/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Ratos , Células Tumorais Cultivadas
17.
Anticancer Res ; 39(7): 3493-3498, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262873

RESUMO

BACKGROUND/AIM: Pancreatic cancer is the most lethal cancer of the digestive system. IL-29 is a new member of the IFNλ family and well-known for its strong antiviral activity. However, its direct effect on pancreatic cancer is still unclear. This study was performed to investigate if IL-29 has any direct effect on Pan-48 pancreatic cancer cells. MATERIALS AND METHODS: Clonogenic survival assay, cell proliferation, and caspase-3 activity kits were used to evaluate the effects of IL-29 on cell survival, proliferation, and apoptosis of Pan-48 pancreatic cancer cells. RT-PCR and IHC were subsequently performed to explore IL-29's potential molecular mechanisms. RESULTS: The percentage of colonies of Pan-48 cells was decreased following the addition of IL-29. This was consistent with a decreased optical density (OD) value of cancer cells. Furthermore, the relative caspase-3 activity in cancer cells was increased after the addition of IL-29, indicating increased apoptosis of cancer cells. The anti-proliferative effect of IL-29 on cancer cells correlated with increased expression of the anti-proliferative molecule p21. The pro-apoptotic effect of IL-29 on cancer cells correlated with an increased expression of the pro-apoptotic molecule Bax. CONCLUSION: IL-29 constrains Pan-48 pancreatic cell growth via up-regulation of p21 and Bax. Our study suggests a potential use of IL-29 in immunotherapy for pancreatic cancer treatment.


Assuntos
Antineoplásicos/farmacologia , Inibidor de Quinase Dependente de Ciclina p21/genética , Interleucinas/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Proteína X Associada a bcl-2/genética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , RNA Mensageiro/metabolismo , Regulação para Cima , Proteína X Associada a bcl-2/metabolismo
18.
Medicine (Baltimore) ; 98(30): e16567, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348284

RESUMO

RATIONALE: Multiple myeloma is the second most common hematological malignancy. Extramedullary involvement is one of the indicators of poor prognosis. There is no consensus in treatment options and the efficacy. This article reports a case of multiple myeloma with onset of pancreas involvement. Amyloidosis secondary to multiple myeloma and a partial response to the chemotherapy treatment further emphasized its rarity. PATIENT CONCERNS: In this article, we report a 59-year-old male patient with a chief complaint of fatigue for 8 months and upper abdominal pain for 2 months. DIAGNOSIS: The patients were diagnosed as amyloidosis secondary to multiple myeloma with pancreatic occupying (head-neck junction area) lesion based on laboratory examination and pathology from lymph node puncture and skin biopsy. INTERVENTIONS: An intensive chemotherapy treatment as bortezomib, lenalidomide, dexamethasone, cisplatin, epirubicin, cyclophosphamide, and etoposide was given. Due to intolerance, treatment regimen was further adjusted to bortezomib, lenalidomide, and dexamethasone. OUTCOMES: The patient was 12 months alive. After 4 cycles of chemotherapy, a partial response was achieved and abdominal magnetic resonance imaging suggested a reduced pancreatic occupying lesion. LESSONS: This case demonstrates that pancreatic involvement, digestive system neoplasm, and amyloidosis-related clinical features may be the earliest manifestations of multiple myeloma. For these patients, an intensive chemotherapy regimen may be a possible treatment approach.


Assuntos
Amiloidose/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/patologia , Neoplasias Pancreáticas/secundário , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico
19.
Cancer Treat Rev ; 78: 17-30, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31325788

RESUMO

INTRODUCTION: Immune checkpoint inhibitors, targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and the programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathways have shown remarkable potential in several types of cancer. In this review we summarize published and ongoing studies on checkpoint inhibitors in pancreatic cancer (PC). METHODS: We conducted a systematic literature search using Medline and Embase up to November 2018; additional data from a search on clinicaltrials.gov were included. Endpoints of interest encompassed overall survival (OS), progression free survival (PFS) and response rates. RESULTS: Full-length articles constituted a minority of included records. Furthermore, few patients were enrolled, and only few phase II studies were identified. Disappointing limited activity was demonstrated with single-agent checkpoint inhibitors in PC. A small number of studies on combination therapy showed promise with regards to response. But overall, PC patients treated with checkpoint inhibitors were not shown to elicit improvement in response rates or overall survival. CONCLUSION: Checkpoint inhibition monotherapy has failed to elicit efficacy in patients with pancreatic cancer. Combination regimens including chemotherapy have shown initial promise, but these results need to be verified. Numerous studies on checkpoint inhibition in PC are ongoing.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Genes cdc , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Humanos , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia
20.
Cancer Sci ; 110(10): 3296-3305, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31348600

RESUMO

Tissue factor (TF) is known to be overexpressed in various cancers including pancreatic cancer. The upregulation of TF expression has been observed not only in tumor cells, but also in tumor stromal cells. Because of the potential of TF as a delivery target, several studies investigated the effectiveness of Ab-drug conjugates (ADCs) against TF for cancer therapy. However, it is still unclear whether anti-TF ADC can exert toxicity against both tumor cells and tumor stromal cells. Here, we prepared ADC using a rat anti-mouse TF mAb (clone.1157) and 2 types of in vivo murine pancreatic cancer models, one s.c. and other orthotopic with an abundant tumor stroma. We also compared the feasibility of bis-alkylating conjugation (bisAlk) with that of conventional maleimide-based conjugation (MC). In the s.c. models, anti-TF ADC showed greater antitumor effects than control ADC. The results also indicated that the bisAlk linker might be more suitable than the MC linker for cancer treatments. In the orthotopic model, anti-TF ADC showed greater in vivo efficacy and more extended survival time control ADC. Treatment with anti-TF ADC (20 mg/kg, three times a week) did not affect mouse body weight changes in any in vivo experiment. Furthermore, immunofluorescence staining indicated that anti-TF ADC delivered agents not only to TF-positive tumor cells, but also to TF-positive tumor vascular endothelial cells and other tumor stromal cells. We conclude that anti-TF ADC should be a selective and potent drug for pancreatic cancer therapy.


Assuntos
Alquilantes/química , Antineoplásicos Imunológicos/administração & dosagem , Imunoconjugados/administração & dosagem , Maleimidas/química , Neoplasias Pancreáticas/tratamento farmacológico , Tromboplastina/antagonistas & inibidores , Animais , Antineoplásicos Imunológicos/química , Antineoplásicos Imunológicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Esquema de Medicação , Feminino , Humanos , Imunoconjugados/química , Imunoconjugados/farmacologia , Camundongos , Camundongos Transgênicos , Neoplasias Pancreáticas/metabolismo , Ratos , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Células Estromais/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
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