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1.
BMC Bioinformatics ; 21(Suppl 14): 364, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998700

RESUMO

BACKGROUND: Machine learning has been utilized to predict cancer drug response from multi-omics data generated from sensitivities of cancer cell lines to different therapeutic compounds. Here, we build machine learning models using gene expression data from patients' primary tumor tissues to predict whether a patient will respond positively or negatively to two chemotherapeutics: 5-Fluorouracil and Gemcitabine. RESULTS: We focused on 5-Fluorouracil and Gemcitabine because based on our exclusion criteria, they provide the largest numbers of patients within TCGA. Normalized gene expression data were clustered and used as the input features for the study. We used matching clinical trial data to ascertain the response of these patients via multiple classification methods. Multiple clustering and classification methods were compared for prediction accuracy of drug response. Clara and random forest were found to be the best clustering and classification methods, respectively. The results show our models predict with up to 86% accuracy; despite the study's limitation of sample size. We also found the genes most informative for predicting drug response were enriched in well-known cancer signaling pathways and highlighted their potential significance in chemotherapy prognosis. CONCLUSIONS: Primary tumor gene expression is a good predictor of cancer drug response. Investment in larger datasets containing both patient gene expression and drug response is needed to support future work of machine learning models. Ultimately, such predictive models may aid oncologists with making critical treatment decisions.


Assuntos
Antineoplásicos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Aprendizado de Máquina , Antineoplásicos/uso terapêutico , Área Sob a Curva , Análise por Conglomerados , Bases de Dados Genéticas , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Fluoruracila/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Curva ROC
2.
Medicine (Baltimore) ; 99(39): e22250, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991420

RESUMO

It is unclear whether the use of antibiotics is related to the efficacy of gemcitabine plus nab-paclitaxel (GnP). Therefore, we investigated the association between the use of antibiotics and efficacy of GnP.We conducted a retrospective single center study from January 2014 to December 2018 in Hokkaido University Hospital.Ninety-nine patients were eligible for the study. Thirty-seven used antibiotics (U) and 62 did not use antibiotics (NU) during GnP therapy. In the U group, 15 patients used ß-lactam antibiotics, 21 used new quinolones, and 1 used carbapenem. The median progression-free survival was 5.8 and 2.7 months (hazards ratio [HR] .602, 95% confidence interval [CI] .391-.928, P = .022) and the median overall survival was 11.0 and 8.4 months (HR .768, 95% CI .491-1.202, P = .248) in the U and not use antibiotics groups, respectively. Antibiotic use (HR .489, 95% CI .287-.832, P = .008) and locally advanced pancreatic cancer (HR 1.808, 95% CI 1.051-3.112, P = .032) were independent prognostic factors for progression-free survival.Antibiotic use was associated with a higher efficacy of GnP, and therefore, it may be employed as a novel treatment strategy.


Assuntos
Adenocarcinoma/tratamento farmacológico , Albuminas/uso terapêutico , Antibacterianos/uso terapêutico , Desoxicitidina/análogos & derivados , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos , Protocolos de Quimioterapia Combinada Antineoplásica , Estudos de Casos e Controles , Quimioterapia Adjuvante/métodos , Desoxicitidina/uso terapêutico , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Estudos Retrospectivos
3.
Medicine (Baltimore) ; 99(38): e22329, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957401

RESUMO

RATIONALE: A supernumerary kidney is an extremely rare renal anomaly. Currently, <100 cases are reported in the literature. There are only 2 right unilateral supernumerary kidneys reported in the literature thus far, but no confirmed cases of urothelial carcinoma in supernumerary kidneys. We report a case of a right supernumerary with urothelial carcinoma, which is, to the best of our knowledge, reported for the first time. PATIENT CONCERNS: A 73-year-old female patient presented with intermittent, painless, whole course and gross hematuria for about 3 months. Her physical and laboratory examinations did not reveal any significant findings except positive occult blood in routine urine examination. Contrast-enhanced spiral computed tomography revealed a dysplastic supernumerary kidney under the normal right kidney. DIAGNOSES: The ureteroscopy showed that the ureter was Y-shaped in the middle part. The medial ureter led to a normal kidney. The lateral ureter was just 2 cm and led to a small cavity in which there was a mass whose biopsy showed urothelial carcinoma. The patient was subsequently diagnosed with a right supernumerary kidney with urothelial carcinoma. INTERVENTION: Nephroureterectomy, including the right normal and supernumerary kidneys, and partial cystectomy by laparoscopy were performed after the ureteroscopy. The patient then received 6 cycles of gemcitabine and cisplatin regimen chemotherapy and regular intravesical epirubicin chemotherapy. OUTCOMES: No recurrence or metastasis was found on follow-up computed tomography performed 13 months postoperatively. LESSONS: A supernumerary kidney is an extremely rare renal anomaly. Malignancy can occur in supernumerary kidneys.


Assuntos
Carcinoma de Células de Transição/terapia , Neoplasias Renais/terapia , Rim/anormalidades , Idoso , Antineoplásicos/uso terapêutico , Carcinoma de Células de Transição/diagnóstico por imagem , Carcinoma de Células de Transição/patologia , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Humanos , Rim/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Nefroureterectomia , Ureter/anormalidades
4.
Anticancer Res ; 40(9): 4969-4978, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878785

RESUMO

BACKGROUND/AIM: Traditional Chinese medicine (TCM) Brucea javanica (BJO) has shown anti-proliferation efficacy on human carcinoma cells in vitro. The aim of the present study was to evaluate for the first time the efficacy of BJO combined with the first-line chemotherapeutic drug gemcitabine (GEM) on tumor growth-inhibition and survival in a pancreatic cancer patient-derived orthotopic xenograft (PDOX) mouse model. MATERIALS AND METHODS: The pancreatic cancer tumor fragment originated from a patient at the Hefei First People's Hospital (Anhui, PR China). The surgical specimen was transplanted orthotopically in nude mice using surgical orthotopic implantation (SOI). All mice were randomized and assigned to 5 groups: G1: saline vehicle (0.1ml per mouse, oral, once per day); G2: GEM [100 mg/kg, intraperitoneal (i.p), twice per week]; G3: GEM+BJO [100 mg/kg GEM, i.p, twice per week+1g/kg BJO, oral, once per day (qd)]; G4: BJO (1g/kg, oral, qd). Group 5 and Group 6 were used to observe survival [G5: saline vehicle (0.1ml per mouse, oral, qd), G6: BJO (1g/kg, oral, qd)]. Body weight and tumor volume were measured twice per week. TUNEL staining was used to determine apoptosis. RESULTS: The combination of GEM + BJO resulted in a reduced tumor growth rate (p<0.05) and greater apoptosis (p<0.05) compared to the vehicle control and GEM monotherapy. In addition, the BJO-treated group showed a statistically significant increase in survival compared to the vehicle control (p<0.05). CONCLUSION: BJO is a promising non-toxic TCM to effectively treat pancreatic cancer, both as monotherapy and in combination with first-line GEM therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Brucea/química , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Desoxicitidina/uso terapêutico , Sinergismo Farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Humanos , Camundongos , Camundongos Nus , Neoplasias Pancreáticas/patologia , Óleos Vegetais/uso terapêutico , Análise de Sobrevida , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Medicine (Baltimore) ; 99(34): e21936, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846862

RESUMO

RATIONALE: IgG4-related disease (IgG4-RD) is a systemic disease that can involve various organs and is characterized by the infiltrations of IgG4-positive plasma cells and lymphocytes, fibrosis, and elevated serum IgG4 levels. IgG4-related sclerosing cholangitis (IgG4-RSC) is a subtype of IgG4-RD. No certain relationship between IgG4-RSC and cholangiocarcinoma has been established as yet, and there have been few reports of the simultaneous diagnosis of IgG4-RSC and cholangiocarcinoma. PATIENT CONCERNS: A 76-year-old male visited our gastroenterology department due to the recent occurrence of pruritus and jaundice. DIAGNOSIS: Computed tomography (CT) scan showed ductal wall swelling and enhancement from both intrahepatic duct confluence to the common bile duct, upper biliary dilatation, and accompanying autoimmune pancreatitis (a sub type of IgG4-RD). Biopsy of the distal common bile duct by endoscopic retrograde cholangiopancreatography (ERCP) resulted in a diagnosis of IgG4-RSC. Subsequently, adenocarcinoma was identified by repeated cytology of bile juice. Finally, Klatskin tumor type IIIA and IgG4-RSC were concurrently diagnosed. INTERVENTIONS: IgG4-RSC was treated with steroid and Klatskin tumors by gemcitabine + cisplatin chemotherapy. OUTCOMES: The jaundice had improved and CT showed substantial improvement of the intrahepatic duct dilatation. LESSONS: IgG4-RSC and cholangiocarcinoma are easily confused, but their treatments are quite different, and thus, care must be taken during diagnosis. Furthermore, these 2 diseases may co-exist. Therefore, even if IgG4-RSC is diagnosed first, the possibility of accompanying cholangiocarcinoma should be thoroughly investigated.


Assuntos
Colangiocarcinoma/complicações , Colangite Esclerosante/patologia , Imunoglobulina G/imunologia , Tumor de Klatskin/complicações , Tumor de Klatskin/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Colangiocarcinoma/patologia , Colangiopancreatografia Retrógrada Endoscópica , Colangite Esclerosante/diagnóstico por imagem , Colangite Esclerosante/tratamento farmacológico , Cisplatino/uso terapêutico , Ducto Colédoco/patologia , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Diagnóstico Diferencial , Humanos , Doença Relacionada a Imunoglobulina G4/patologia , Icterícia/diagnóstico , Icterícia/etiologia , Tumor de Klatskin/classificação , Tumor de Klatskin/tratamento farmacológico , Masculino , Prurido/diagnóstico , Prurido/etiologia , Esteroides/uso terapêutico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
6.
Medicine (Baltimore) ; 99(28): e21041, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664114

RESUMO

BACKGROUND: Many research has indicated that some Chinese herb injections (CHIs) might be beneficial in combination with chemotherapy, however, with inconsistent results. Hence, the purpose of this network meta-analysis is to evaluate different CHIs plus cisplatin and gemcitabine (GP) with GP alone in terms of clinical efficacy and safety for treating patients with advanced NSCLC. METHODS: A comprehensive systematic search of clinical randomized controlled trials (RCTs) published in the PubMed, Embase, Web of Science (ISI), Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang Database and China Biological Medicine Database (CBM) databases will be conducted to identify eligible studies up to the date of May 2020. The primary outcome measures objective response rate and adverse reactions (nausea and vomiting, leukopenia). The secondary outcome measures median survival time (MST), disease control rate, and quality of life. The methodological qualities, including the risk of bias, will be evaluated using the Cochrane risk of bias assessment tool, while confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The network meta-analysis will be performed using WinBUGS 14 and Stata 15.1 software. RESULTS: Based on the current evidence, the potential rank of the efficacy and safety of CHIs plus GP chemotherapy for advanced NSCLC will be assessed, and a prioritization regimen will be summarized. CONCLUSION: Evidence from this systematic review could be useful for patients, clinical practitioners, and guideline-makers to select an optimum proposal of CHIs plus GP for advanced NSCLC. ETHICS AND DISSEMINATION: It is not necessary for ethical approval because it is based on published studies. The protocol will be disseminated in a peer-reviewed journal or presented at a topic-related conference. PROSPERO REGISTRATION NUMBER: CRD42020167142.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Projetos de Pesquisa , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Medicamentos de Ervas Chinesas/administração & dosagem , Humanos , Metanálise em Rede , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida
7.
Anticancer Res ; 40(7): 3659-3667, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620605

RESUMO

BACKGROUND/AIM: FOLFIRINOX [fluorouracil (5-FU), irinotecan, oxaliplatin] and gemcitabine plus nab-paclitaxel are standard treatments for patients with pancreatic ductal adenocarcinoma (PDAC). Despite efficacy rates of less than 32%, evidence is lacking to guide the use of one drug over the other. Herein, we compared the sensitivity of patient-derived PDAC cell lines to each of these regimens. MATERIALS AND METHODS: Changes in the growth of 19 low-passage patient-derived PDAC cell lines were evaluated in response to treatment with FOLFIRINOX and gemcitabine plus paclitaxel (Gem-Pac). RESULTS: Six cell lines exhibited optimal sensitivity (high EMax and low GI50) to FOLFIRINOX and three cell lines exhibited optimal sensitivity to Gem-Pac. Several cell lines that were optimally sensitive to one drug regimen exhibited very poor response to the other. CONCLUSION: Further characterization of cancer cells exhibiting preferential sensitivity to each of these regimens may allow the identification of biomarkers to guide the selection of appropriate chemotherapy for a given patient.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Desoxicitidina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oxaliplatina/uso terapêutico
8.
Anticancer Res ; 40(7): 4011-4015, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620645

RESUMO

BACKGROUND/AIM: The aim of this monocentric study was to evaluate the efficacy and tolerability of a polychemotherapy regimen based on gemcitabine, docetaxel, capecitabine, cisplatin (PDGX) as second-line for advanced pancreatic cancer after FOLFIRINOX. PATIENTS AND METHODS: Patients received FOLFIRINOX as first-line regimen were retrospectively identified between January 2016 and January 2019. After disease progression or unacceptable toxicity, patients eligible for second-line therapy were treated in our center by PDGX. RESULTS: During this period, 18 patients received PDGX regimen as second-line therapy. Main grade 3 toxicities were hematologic, which required dose adaptation in 14/18 patients. No toxic death was observed. Median second-line progression-free survival (PFS) and overall survival (OS) were 2,91 and 5,3 months, respectively. Total OS from the initiation of first-line was and 11,9 months. CONCLUSION: Second-line PDGX regimen after FOLFIRINOX failure is feasible, with notable toxicity profile and is associated with poor clinical outcomes.


Assuntos
Adenocarcinoma/tratamento farmacológico , Capecitabina/uso terapêutico , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Docetaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/mortalidade , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/efeitos adversos , Cisplatino/efeitos adversos , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Docetaxel/efeitos adversos , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/mortalidade , Resultado do Tratamento
9.
Int J Clin Oncol ; 25(10): 1835-1843, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32535711

RESUMO

BACKGROUND: A family/personal history of breast, ovarian, or pancreatic cancer is a useful predictive marker for response to platinum-based chemotherapy in treating patients with pancreatic cancer. These cancers, and prostate cancer, are known as BRCA-related malignancies. We evaluated the efficacy of gemcitabine plus oxaliplatin (GEMOX) in patients with metastatic pancreatic cancer with a family/personal history of these cancers. METHODS: Chemotherapy-naïve patients with metastatic pancreatic cancer with a family history of pancreatic/breast/ovarian/prostate cancer or a personal history of breast/ovarian/prostate cancer were included. Patients received fixed dose-rate gemcitabine (1000 mg/m2) and oxaliplatin (100 mg/m2) every 2 weeks. The primary endpoint was 1-year survival, and the threshold and expected values were set at 30 and 50%, respectively. The target sample size was determined to be 43, with a one-sided alpha value of 5% and power of 80%. A total of 45 patients were enrolled. RESULTS: Among the first 43 enrolled patients, the 1-year survival rate was 27.9% [90% confidence interval (CI) 17.0-41.3], which did not meet the primary endpoint. Median overall survival, progression-free survival, and response rates were 7.6 months (95% CI 6.0-10.7), 4.0 months (95% CI 2.0-4.6), and 26.7% (95% CI 14.6-41.9), respectively, in all registered patients. The GEMOX regimen was generally tolerated; the most common grade three or higher adverse events were hematological toxicities. CONCLUSION: GEMOX did not show the expected efficacy in patients with metastatic pancreatic cancer with a family or personal history of pancreatic/breast/ovarian/prostate cancer. Selection of GEMOX based on family/personal history is not recommended. TRIAL REGISTRATION NUMBER: UMIN000017894.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Neoplasias da Mama , Desoxicitidina/uso terapêutico , Feminino , Humanos , Masculino , Anamnese , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Neoplasias Ovarianas , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Intervalo Livre de Progressão , Neoplasias da Próstata , Taxa de Sobrevida , Resultado do Tratamento
10.
Zhongguo Zhen Jiu ; 40(6): 596-600, 2020 Jun 12.
Artigo em Chinês | MEDLINE | ID: mdl-32538008

RESUMO

OBJECTIVE: To observe the prevention effect of transcutaneous electrical acupoint stimulation (TEAS) for chemotherapy-related myelosuppression in non-small cell lung cancer. METHODS: A total of 102 patients with non-small cell lung cancer who received initial chemotherapy were randomly divided into a conventional group, a medication group and a TEAS group, 34 cases in each one. The conventional group was treated with chemotherapy of gemcitabine combined with cisplatin and given routine care. On the basis of conventional group's treatment, the medication group was given Diyu Shengbai tablets before chemotherapy, 2-3 tablets each time, 3 times a day. In the TEAS group, on the basis of conventional group's treatment, TEAS was applied at Dazhui (GV 14), Geshu (BL 17), Hegu (LI 4), Zusanli (ST 36) and Sanyinjiao (SP 6) on day 1, 2, 3, 5, 8, 14, 21 and 28 of chemotherapy. The treatment was given 30 min each time and once a day. In the three groups, the treatment for 28 days was as one course and one course of treatment was required. The changes of leukocytes, platelets, erythrocyte, hemoglobin indexes in patients of the three groups were observed one day before chemotherapy and on day 5, 8, 11, 14, 21 and 28 of chemotherapy. The comfort situation of patients was observed one day before chemotherapy and on the 5th, 11th and 21st day of chemotherapy. RESULTS: Compared with before chemotherapy, the leukocyte counts of three groups were decreased at various time points after chemotherapy (P<0.05). Compared with the conventional group, the leukocyte counts were higher on day 8 and 14 in the TEAS group and on day 14 in the medication group (P<0.05). Compared with before chemotherapy, the platelet count decreased on the day 5, 8, 11 and 14 of chemotherapy in the conventional group (P<0.05), and the platelet counts all decreased at each time point after chemotherapy in the medication group (P<0.05). The platelet counts of the TEAS group on day 5, 8, 11 and 14 of chemotherapy were higher than those of the conventional group (P<0.05), and the platelet counts of the TEAS group on day 5, 8, 11 and 21 of chemotherapy were higher than those of the medication group (P<0.05). Compared with the conventional group, the comfort situation scores of the TEAS group were higher on the 5th and 11th days of chemotherapy (P<0.05). CONCLUSION: Transcutaneous electrical acupoint stimulation can prevent chemotherapy-induced myelosuppression (leukocyte, platelets) in patients with non-small cell lung cancer and improve patient comfort situation.


Assuntos
Medula Óssea/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/terapia , Estimulação Elétrica Nervosa Transcutânea , Pontos de Acupuntura , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos
11.
Medicine (Baltimore) ; 99(22): e20499, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481467

RESUMO

INTRODUCTION: Primary transitional cell carcinoma (TCC) of the fallopian tube is an extremely rare tumor. PATIENT CONCERNS: A 79-year-old woman presenting with vaginal discharge. DIAGNOSIS: Pelvic magnetic resonance imaging revealed a predominantly solid mass with a lobulated contour, measuring 5.5 cm × 4.6 cm, in the left ovary. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. Pathological analysis revealed a high-grade TCC, measuring 7.5 cm × 4 cm, in the left fallopian tube (International Federation of Gynecology and Obstetrics stage IIB). INTERVENTION: Forty-three months postoperation, recurrence was diagnosed as peritoneal metastasis. The patient underwent 6 cycles of palliative chemotherapy consisting of cisplatin and gemcitabine, the recommended regimen for TCC of the urinary tract. OUTCOME: The patient has survived for 27 months without recurrence after palliative chemotherapy, 76 months after diagnosis. CONCLUSION: It is rare that primary TCC of the fallopian tube responds to a urinary tract treatment regimen for TCC, even when followed up for an extended period. More research is warranted to determine which treatment regimen will benefit patients the most.


Assuntos
Carcinoma de Células de Transição/diagnóstico por imagem , Carcinoma de Células de Transição/cirurgia , Neoplasias das Tubas Uterinas/diagnóstico por imagem , Neoplasias das Tubas Uterinas/cirurgia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/patologia , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Histerectomia , Imagem por Ressonância Magnética , Recidiva Local de Neoplasia/tratamento farmacológico , Cuidados Paliativos , Salpingo-Ooforectomia
13.
Cancer Control ; 27(1): 1073274820915947, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32268796

RESUMO

Lymphatic metastasis is a major determinant of the outcome of resected pancreatic cancer. Gemcitabine-based adjuvant chemotherapy can improve the outcome of resected pancreatic cancer. However, the efficacy of gemcitabine against pancreatic cancer stratified by nodal involvement is unclear. In this study, patients who had undergone curative resection of pancreatic adenocarcinoma (612 cases) were included. The efficacy of adjuvant gemcitabine-based regimen, stratified by nodal status (negative, positive) or N substage (N0, no nodal involvement; N1, 1-3-node involvement; N2, ≥4-node involvement), was examined. Both the node-negative (hazard ratio [HR] = 0.62, 95% confidence interval [CI], 0.44-0.87, P = .006) and node-positive subgroups (HR = 0.45, 95% CI, 0.33-0.62, P < .001) benefited from gemcitabine-based adjuvant chemotherapy. Patients with N0 (ie, the node-negative subgroup) or N1 (HR = 0.36, 95% CI, 0.25-0.52, P < .001) disease benefited from gemcitabine-based chemotherapy. However, patients with N2 tumors (HR = 0.95, 95% CI, 0.50-1.78, P = .867) had poor response to gemcitabine-based treatment. Therefore, we postulate that resected pancreatic cancer with N2 node involvement is refractory to gemcitabine-based adjuvant chemotherapy. A more intensive adjuvant regimen may be required for N2 subgroup patients.


Assuntos
Quimioterapia Adjuvante/métodos , Desoxicitidina/análogos & derivados , Linfonodos/efeitos dos fármacos , Metástase Linfática/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade
14.
Int J Clin Pract ; 74(7): e13510, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32279393

RESUMO

BACKGROUND: Gemcitabine has been proved to be effective in many advanced cancer. However, almost all trials failed to demonstrate the response rate of gemcitabine-based combination schedules on oesophageal cancer (EC). METHODS: A systematic meta-analysis of randomised clinical trials (RCTs) was performed to investigate the efficacy of gemcitabine-based combination chemotherapy in EC treatment. Clinical trials were collected during the period ranging from January 2000 to November 2018 by searching different databases. Odds-ratios (ORs) of response rate (RR), disease control rate (DCR) and grade 3-4 toxicity rates (TRs) were extracted as presented in retrieved studies. RESULTS: Fourteen trials (1024 patients) were selected for the final analysis. The results showed that RR and DCR of gemcitabine-based combination chemotherapy demonstrated a significant advantage for non-gemcitabine therapy (OR for RR: 1.51; 95% CI: 1.16-1.96; P = .002; OR for DCR: 1.66; 95% CI: 1.19-2.32, P = .003). Toxicities of gemcitabine-based combination chemotherapy on gastrointestinal tract (OR, 0.39; 95% CI: 0.24-0.63, P = .0001) were less frequent compared to that of the non-gemcitabine therapy. CONCLUSION: The improvements of gemcitabine-based combination chemotherapy on RR, CDR and reduction of gastrointestinal tract, hepatic and renal for EC patients suggests that the combined chemotherapy based on gemcitabine could be a potential treatment options for advanced EC.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Neoplasias Esofágicas/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Administração Intravesical , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/uso terapêutico , Progressão da Doença , Esquema de Medicação , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Am J Clin Oncol ; 43(6): 435-441, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32251119

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma is a largely incurable cancer. Surgical resection remains the only potential option for cure. Even in surgically resectable patients, only about 10% to 20% are long-term survivors. Emerging data suggest a role for neoadjuvant therapy to target occult micrometastatic disease. AIM: To report our institutional experience with a novel neoadjuvant chemoradiation (CRT) regimen in resectable and borderline resectable pancreatic cancer. MATERIALS AND METHODS: Patients were treated with 2 cycles of induction chemotherapy with FOLFOX and then received CRT with gemcitabine and intensity-modulated radiotherapy (IMRT). RESULTS: From April 2014 to June 2017, 24 patients were enrolled. Eighteen patients were borderline resectable and 6 patients were resectable. All patients received induction chemotherapy with FOLFOX. Thirteen patients underwent pancreatectomy after CRT with a resection rate of 62%. R0 resection achieved in 11 patients (84.6%) and 2 patients had R1 resection (15.4%). For patients who underwent resection, the median progression-free survival (PFS) was 31 months, 1-year PFS rate was 69.2% (95% confidence interval [CI], 0.48-0.99), and 2-year PFS rate was 51.9% (95% CI, 0.3-0.89). Median overall survival (OS) was 34.8 months (95% CI, 1.045 to infinity), 1-year OS rate was 91.7% (95% CI, 0.77-1.0), and 2-year OS rate was 75% (95% CI, 0.54-1.0). Median CA 19-9 at screening for patients who underwent surgery was 659 (range, 18 to 2154), which decreased to 146.9 (range, 18 to 462) after CRT before resection. CONCLUSION: Neoadjuvant therapy for borderline resectable and resectable pancreatic ductal adenocarcinoma with CRT facilitated R0 resection in 84% patients who underwent surgery.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/terapia , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/terapia , Radioterapia de Intensidade Modulada , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/cirurgia , Quimiorradioterapia , Desoxicitidina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Quimioterapia de Indução , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Compostos Organoplatínicos/uso terapêutico , Neoplasias Pancreáticas/cirurgia
16.
Microb Cell Fact ; 19(1): 75, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32204699

RESUMO

Resistance to therapy is one of the major factors that contribute to dismal survival statistics in pancreatic cancer. While there are many tumor intrinsic and tumor microenvironment driven factors that contribute to therapy resistance, whether pre-existing metabolic diseases like type 2 diabetes (T2D) contribute to this has remained understudied. It is well accepted that hyperglycemia associated with type 2 diabetes changes the gut microbiome. Further, hyperglycemia also enriches for a "stem-like" population within the tumor. In the current study, we observed that in a T2D mouse model, the microbiome changed significantly as the hyperglycemia developed in these animals. Our results further showed that, tumors implanted in the T2D mice responded poorly to gemcitabine/paclitaxel (Gem/Pac) standard of care compared to those in the control group. A metabolomic reconstruction of the WGS of the gut microbiota further revealed that an enrichment of bacterial population involved in drug metabolism in the T2D group. Additionally, we also observed an increase in the CD133+ tumor cells population in the T2D model. These observations indicated that in an animal model for T2D, microbial dysbiosis is associated with increased resistance to chemotherapeutic compounds.


Assuntos
Diabetes Mellitus Tipo 2/microbiologia , Resistencia a Medicamentos Antineoplásicos , Disbiose/microbiologia , Hiperglicemia/microbiologia , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Microbioma Gastrointestinal , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/microbiologia
17.
BMC Cancer ; 20(1): 203, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164564

RESUMO

BACKGROUND: The current study aimed to evaluate the outcomes of patients with unresectable non-metastatic locally advanced pancreatic adenocarcinoma (LAPA) who did not benefit from resection considering the treatment strategy in the clinical settings. METHODS: Between 2010 and 2017, a total of 234 patients underwent induction chemotherapy for LAPA that could not be treated with surgery. After oncologic restaging, continuous chemotherapy or chemoradiation (CRT) was decided for patients without metastatic disease. The Kaplan-Meier method was used to determine overall survival (OS), and the Wilcoxon test to compare survival curves. Multivariate analysis was performed using the stepwise logistic regression method. RESULTS: FOLFIRINOX was the most common induction regimen (168 patients, 72%), with a median of 6 chemotherapy cycles and resulted in higher OS, compared to gemcitabine (19 vs. 16 months, hazard ratio (HR) = 1.2, 95% confidence interval: 0.86-1.6, P = .03). However, no difference was observed after adjusting for age (≤75 years) and performance status score (0-1). At restaging, 187 patients (80%) had non-metastatic disease: CRT was administered to 126 patients (67%) while chemotherapy was continued in 61 (33%). Patients who received CRT had characteristics comparable to those who continued with chemotherapy, with similar OS. They also had longer progression-free survival (median 13.3 vs. 9.6 months, HR = 1.38, 95% confidence interval: 1-1.9, P < .01) and limited short-term treatment-related toxicity. CONCLUSIONS: The median survival of patients who could not undergo surgery was 19 months. Hence, CRT should not be eliminated as a treatment option and may be useful as a part of optimised sequential chemotherapy for both local and metastatic disease.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Desoxicitidina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Estudos Prospectivos , Análise de Sobrevida , Resultado do Tratamento
18.
JAMA Netw Open ; 3(3): e200452, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32134464

RESUMO

Importance: The Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database may provide insights into the comparative effectiveness of oncological treatments for elderly individuals who are underrepresented in clinical trials. Objective: To evaluate the suitability of SEER-Medicare data for assessing the effectiveness of adding a drug to an existing treatment regimen on the overall survival of elderly patients with cancer. Design, Setting, and Participants: This comparative effectiveness study analyzed SEER-Medicare data from 9549 individuals who received a new diagnosis of stage II colorectal cancer (2008-2012) and 940 patients who received a new diagnosis of advanced pancreatic adenocarcinoma (2007-2012), with follow-up to December 31, 2013 (SEER-Medicare data released in 2015). Two (hypothetical) target trials were designed and emulated based on 2 existing randomized clinical trials: (1) adjuvant fluorouracil after curative surgery for individuals with stage II colorectal cancer and (2) erlotinib added to gemcitabine for individuals with advanced pancreatic adenocarcinoma. Data were analyzed January 2018 to March 2019. Exposures: The following treatment strategies were compared: (1) fluorouracil initiation vs no initiation within 3 months of tumor resection and (2) erlotinib initiation vs no initiation within 12 weeks of gemcitabine initiation. Main Outcomes and Measures: All-cause mortality within 60 months of baseline for the fluorouracil trial and within 72 weeks for the erlotinib trial. Results: Compared with 3293 individuals in the existing fluorouracil trial, 9549 eligible individuals included in the present analyses were more likely to have colon cancer (8565 [90%] vs 2291 [71%]) and were older (median [interquartile range], 79 [73-84] vs 63 [56-68] years). The 5-year risk difference for initiation vs noninitiation of fluorouracil after surgery was -3.8% (95% CI, -14.8% to 12.6%), and the mortality hazard ratio (HR) was 0.95 (95% CI, 0.85-1.04). Compared with 569 individuals in the existing erlotinib trial, 940 eligible patients included in the present analysis were older (median [range], 74 [66-93] vs 64 [36-92] years) and more likely to be male (547 [58%] vs 298 [52%]). The 1-year risk difference for initiation vs noninitiation of erlotinib was 4.7% (95% CI, -9.4% to 18.0%), and the corresponding mortality HR was 1.04 (95% CI, 0.86-1.42). In naive analyses, the mortality HR estimate was 1.14 (95% CI, 0.95-1.36) for the fluorouracil emulation and 0.68 (95% CI, 0.54-0.87) for the erlotinib emulation. Conclusions and Relevance: The present estimates were similar to those from randomized clinical trials that studied adding the same cancer drugs to existing regimens. The published HR was 1.02 (95% CI, 0.70-1.48) in the fluorouracil trial for individuals aged 70 or older and 0.96 (95% CI, 0.74-1.24) in the erlotinib trial for individuals aged 65 years or older. The SEER-Medicare database may be adequate for studying the real-world effectiveness of adding a drug to treatment regimens used for elderly individuals with cancer.


Assuntos
Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Neoplasias do Colo/mortalidade , Neoplasias do Colo/terapia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Neoplasias do Colo/patologia , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Cloridrato de Erlotinib/uso terapêutico , Fluoruracila/uso terapêutico , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Programa de SEER , Taxa de Sobrevida , Estados Unidos
19.
PLoS One ; 15(3): e0228557, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32142553

RESUMO

Early diagnosis along with new drugs targeted to cancer receptors and immunocheckpoints have improved breast cancer survival. However, full remission remains elusive for metastatic breast cancer due to dose-limiting toxicities of heavily used, highly potent drug combinations such as gemcitabine and paclitaxel. Therefore, novel strategies that lower the effective dose and improve safety margins could enhance the effect of these drug combinations. To this end, we developed and evaluated a novel drug combination of gemcitabine and paclitaxel (GT). Leveraging a simple and scalable drug-combination nanoparticle platform (DcNP), we successfully prepared an injectable GT combination in DcNP (GT DcNP). Compared to a Cremophor EL/ethanol assisted drug suspension in buffer (CrEL), GT DcNP exhibits about 56-fold and 8.6-fold increases in plasma drug exposure (area under the curve, AUC) and apparent half-life of gemcitabine respectively, and a 2.9-fold increase of AUC for paclitaxel. Using 4T1 as a syngeneic model for breast cancer metastasis, we found that a single GT (20/2 mg/kg) dose in DcNP nearly eliminated colonization in the lungs. This effect was not achievable by a CrEL drug combination at a 5-fold higher dose (i.e., 100/10 mg/kg GT). A dose-response study indicates that GT DcNP provided a therapeutic index of ~15.8. Collectively, these data suggest that GT DcNP could be effective against advancing metastatic breast cancer with a margin of safety. As the DcNP formulation is intentionally designed to be simple, scalable, and long-acting, it may be suitable for clinical development to find effective treatment against metastatic breast cancer.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Nanopartículas/química , Animais , Antineoplásicos/sangue , Antineoplásicos/uso terapêutico , Linhagem Celular , Desoxicitidina/análogos & derivados , Desoxicitidina/sangue , Desoxicitidina/química , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Relação Dose-Resposta a Droga , Composição de Medicamentos , Sinergismo Farmacológico , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Paclitaxel/sangue , Paclitaxel/química , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Resultado do Tratamento
20.
Anticancer Res ; 40(3): 1613-1618, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32132064

RESUMO

BACKGROUND/AIM: To evaluate the efficacy and toxicity of paclitaxel, gemcitabine, and cisplatin (TGP) as second-line treatment for advanced urothelial carcinoma (UC). PATIENTS AND METHODS: This study comprised advanced UC progressed after first-line cisplatin-based chemotherapy. Advanced UC was defined as a non-resectable (T4b, any N or any T, or N2-3) or metastatic disease. Twenty-one patients were included in this study. TGP was administered every 3 weeks. The primary endpoint was objective response rate (ORR); the secondary end points were progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: The ORR with TGP was 23.8%; the median PFS and OS were 4 and 8.4 months, respectively. The primary side effect was myelosuppression. Grade 3-4 neutropenia and thrombocytopenia were observed in 71.4% and 42.9%, respectively. There were no toxic deaths. CONCLUSION: TGP is moderately effective and tolerable as second-line chemotherapy for patients with UC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Paclitaxel/uso terapêutico , Neoplasias Urológicas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Cisplatino/farmacologia , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/farmacologia , Neoplasias Urológicas/patologia
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