RESUMO
BACKGROUND: Cancer stem cells (CSCs) are thought to play important roles in carcinogenesis, recurrence, metastasis, and therapy-resistance. We have successfully induced cancer stem-like sphere cells (CSLCs) which possess enhanced chemoresistance and metastatic potential. To enable the development of targeted therapy against CSLCs, we identified a gene responsible for this phenotype in CSLC. METHODS: Human hepatoma cell line SK-HEP-1 was used for CSLC induction with a unique sphere inducing medium, and HuH-7 cells were used as non-sphere forming cells in the same condition. RNA-sequencing was performed followed by validation with quantitative RT-PCR and western blotting. Knockdown experiments were done by using CRISPR-Cas9 genome-editing, and the rescue experiments were performed using the expressing plasmid vector. Chemoresistance and liver metastasis of the cells, was studied following the splenic injection of cells to severely immune deficient mice and evaluated using the MTS assay. Quantification of exosomes in the medium was done using ELISA. RESULTS: RAB3B was identified as an up-regulated gene in both CSLCs and prognostically poor hepatocellular carcinoma (HCC) by RNA-sequencing. RAB3B-KD cells showed altered CSLC phenotypes such as sphere formation, chemoresistance, and metastatic potentials, and those were rescued by RAB3B complementation. Increased exosome secretion was observed in CSLCs, and it was not observed in the RAB3B-KD cells. In addition, the RAB3B expression correlated with the expression of ABCG2, APOE, LEPR, LXN, and TSPAN13. CONCLUSION: The up regulation of RAB3B may play an important role in the chemoresistance and metastatic potential of CSLCs.
Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Células-Tronco Neoplásicas/metabolismo , Proteínas rab3 de Ligação ao GTP/metabolismo , Animais , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Reação em Cadeia da Polimerase em Tempo Real , Regulação para CimaRESUMO
BACKGROUND: This phase I study aimed to evaluate the safety, peptide-specific immune responses, and anti-tumor effects of a novel vaccination therapy comprising multi-HLA-binding heat shock protein (HSP) 70/glypican-3 (GPC3) peptides and a novel adjuvant combination of hLAG-3Ig and Poly-ICLC against metastatic gastrointestinal cancers. METHODS: HSP70/GPC3 peptides with high binding affinities for three HLA types (A*24:02, A*02:01, and A*02:06) were identified with our peptide prediction system. The peptides were intradermally administered with combined adjuvants on a weekly basis. This study was a phase I dose escalation clinical trial, which was carried out in a three patients' cohort; in total, 11 patients were enrolled for the recommended dose. RESULTS: Seventeen patients received this vaccination therapy without dose-limiting toxicity. All treatment-related adverse events were of grades 1 to 2. Peptide-specific CTL induction by HSP70 and GPC3 proteins was observed in 11 (64.7%) and 13 (76.5%) cases, respectively, regardless of the HLA type. Serum tumor marker levels were decreased in 10 cases (58.8%). Immunological analysis using PBMCs indicated that patients receiving dose level 3 presented with significantly reduced T cell immunoglobulin and mucin-domain containing-3 (TIM3)-expressing CD4 + T cells after one course of treatment. PD-1 or TIM3-expressing CD4 + T cells and T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT)-expressing CD8 + T cells in PBMCs before vaccination were negative predictive factors for survival. CONCLUSIONS: This novel peptide vaccination therapy was safe for patients with metastatic gastrointestinal cancers.
Assuntos
Carboximetilcelulose Sódica/análogos & derivados , Neoplasias Gastrointestinais/terapia , Glipicanas/imunologia , Antígenos HLA-A/imunologia , Antígenos HLA-G/administração & dosagem , Proteínas de Choque Térmico HSP70/imunologia , Fragmentos de Peptídeos/administração & dosagem , Poli I-C/administração & dosagem , Polilisina/análogos & derivados , Adjuvantes Imunológicos/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Carboximetilcelulose Sódica/administração & dosagem , Estudos de Coortes , Feminino , Seguimentos , Neoplasias Gastrointestinais/imunologia , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/patologia , Glipicanas/metabolismo , Antígenos HLA-A/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/metabolismo , Polilisina/administração & dosagem , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: Colorectal cancer is the third most common cancer worldwide. If biomarkers can be identified in liquid biopsy, diagnosis and treatment can be optimized even when cancerous tissues are not available. The purpose of this study was to identify proteins from liquid biopsy that would be useful as markers of poor prognosis. METHODS: First, we comprehensively analyzed serum proteins to identify potential biomarkers and focused on serum lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). The relationship between LOX-1 and the prognosis of patients with colorectal cancer has not been reported. Next, we validated this marker using serum samples from 238 patients with colorectal cancer by ELISA and 100 tissue samples by immunohistochemical staining. RESULTS: The optimal cut-off value of serum LOX-1 was 538.7 pg/mL according to time-dependent receiver operating characteristics curve analysis. The overall survival of patients with high levels of serum LOX-1 was significantly poorer than that of individuals with low levels of LOX-1 in the training and test datasets. In multivariate analysis for overall survival, serum LOX-1 was an independent prognostic factor identified in liquid biopsy (hazard ratio = 1.729, p = 0.027). The prognosis of patients with high LOX-1 expression in tumor tissues was significantly poorer than that of individuals with low expression (p =0.047 ). Additionally, inflammatory factors such as white blood cell count, C-reactive protein level, neutrophil/lymphocyte ratio, and monocyte/lymphocyte ratio were significantly higher in the group with high serum LOX-1 levels. CONCLUSIONS: Serum LOX-1 might be a useful biomarker of poor prognosis in colorectal cancer.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Receptores Depuradores Classe E/sangue , Idoso , Neoplasias Colorretais/patologia , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neutrófilos/patologia , Prognóstico , Curva ROC , Reprodutibilidade dos TestesRESUMO
A 60-year-old man underwent thoracoscopic subtotal esophagectomy and posterior mediastinal gastric tube reconstruction after neoadjuvant chemotherapy. One year and 8 months postoperatively, recurrence was observed in the abdominal lymph nodes around the celiac artery and abdominal aorta. Chemoradiotherapy was initiated, followed by chemotherapy. Two months after the completion of chemoradiotherapy, the patient developed epigastric pain and anorexia because of the necrotic lymph node penetrating the gastric tube with cavity formation. Upper gastrointestinal endoscopy revealed a 25- mm-sized ulcer with central necrotic slough on the posterior wall of the stomach. Abdominal symptoms alleviated after conservative treatment with fasting and administration of antibiotics, and the inflammatory reaction improved. Oral nutritional supplements were started on hospitalization day 7, and abdominal symptoms or inflammatory reactions did not recur after resuming diet. The patient was discharged on hospitalization day 39 when the general condition stabilized. Subsequently, chemotherapy was restarted, and no regrowth of metastatic lesions was observed on endoscopy or CT examination 4 months later. Three years and 8 months after the recurrence, the recurrent disease has been controlled.
Assuntos
Neoplasias Esofágicas , Recidiva Local de Neoplasia , Quimiorradioterapia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Humanos , Linfonodos , Masculino , Pessoa de Meia-IdadeRESUMO
Case 1: The patient was a 74-year-old man with a performance status(PS)of 0. He was referred to our department for pyloric gastric cancer with multiple liver, lung, and lymph node metastases. We started chemotherapy after making the diagnosis of an unresectable gastric cancer. During chemotherapy, the hemoglobin level dropped due to bleeding from the tumor. We attempted endoscopic hemostasis, which was not successful; therefore, we attempted a palliative radiotherapy. The total dose was 30 Gy in 10 Fr and hemostasis was achieved on the 10th day from the start of the radiotherapy. There were no adverse events due to the radiation, and the chemotherapy could be restarted 5 days after the end of the radiotherapy. Case 2: The patient was a 78-year-old man with a PS of 2. He was referred to our department because of vomiting and anemia. As a result of a close inspection, we made the diagnosis of an unresectable gastric body cancer with para-aortic lymph node metastasis and peritoneal dissemination, for which chemotherapy was initiated. Anemia was observed at the first visit, and we started radiotherapy to stop the tumor bleeding. The total dose was 30 Gy in 10 Fr, and hemostasis was achieved on the 12th day. There were no adverse events during the radiotherapy, and chemotherapy could be continued. Palliative radiotherapy is an available method of hemostasis that is less invasive than surgery or transcatheter arterial embolization and can be expected to have a certain effect for gastric cancer bleeding, although it takes several days to obtain a therapeutic effect.
Assuntos
Embolização Terapêutica , Radiação , Neoplasias Gástricas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Humanos , Masculino , Cuidados Paliativos , Neoplasias Gástricas/complicações , Neoplasias Gástricas/radioterapiaRESUMO
BACKGROUND: CD3 + and CD8 + T-cell infiltration were reported as positive predictive markers of survival in colorectal cancer (CRC) patients. Here, we demonstrate the prognostic significance of CD4 + and FOXP3 + T-cell densities in CRC. METHODS: We quantified the intratumoural densities of CD3 + , CD8 + , CD4 + and FOXP3 + T cells by immunohistochemistry and digital pathology in 342 CRC patients who underwent curative resection. Microsatellite instability was also assessed in 322 specimens. Patient demographics, clinicopathological features and survival rates were analysed. RESULTS: High CD3 + , CD4 + and FOXP3 + T-cell densities were associated with improved relapse-free survival (RFS); high CD8 + , CD4 + and FOXP3 + T-cell densities were associated with improved disease-specific survival (DSS). Patients with low CD4 + and low FOXP3 + T-cell densities exhibited extremely poor prognoses. T stage, vascular/lymphatic invasion and CD4 + T-cell density were independent prognostic indicators for DSS. The distributions of CD4 + and FOXP3 + T-cell densities were not significantly different between the high microsatellite instability group and other groups, in contrast to those of CD3 + and CD8 + T-cell densities. CONCLUSIONS: Intratumoural CD4 + T-cell density and combined CD4 + and FOXP3 + T-cell densities were stronger prognostic indicators than other clinicopathological features. These results may facilitate the establishment of novel prognostic factors and therapeutic strategies for CRC.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Carcinoma/imunologia , Neoplasias Colorretais/imunologia , Linfócitos do Interstício Tumoral/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Complexo CD3/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Carcinoma/genética , Carcinoma/patologia , Carcinoma/terapia , Contagem de Células , Quimioterapia Adjuvante , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Subpopulações de Linfócitos T/metabolismoRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMO
Case 1: A 64-year-old man with a chiefcomplaint ofbloody stools was seen in our hospital. He underwent an extended right lobe resection for hilar cholangiocarcinoma 3 years ago and was in the middle of chemotherapy for multiple metastases. Case 2: A 69-year-old man with a chiefcomplaint ofbloody emesis and stools was seen. He underwent left hepatic trisegmentectomy for hilar cholangiocarcinoma and ligation of the right portal vein for postoperative portal venous thrombus 6 months ago. After careful examination, the patients in both cases were diagnosed with bleeding of the jejunal varices formed at the site ofhepaticojejunostomy. The patient in Case 1 underwent percutaneous transhepatic obliteration ofvarices and the patient in Case 2 underwent transileocolic vein obliteration ofvarices. After hepatobiliary pancreatic surgery with biliary tract reconstruction, we should be aware of ectopic varices during differential diagnosis of gastrointestinal bleeding.
Assuntos
Neoplasias dos Ductos Biliares , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma , Tumor de Klatskin , Varizes , Idoso , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/complicações , Colangiocarcinoma/cirurgia , Humanos , Tumor de Klatskin/complicações , Tumor de Klatskin/cirurgia , Masculino , Pessoa de Meia-Idade , Ruptura/etiologia , Varizes/patologiaRESUMO
A 65-year-old woman with cecum cancer underwent laparoscopic right colectomy.After 3 years, she was diagnosed with a local recurrence with small bowel invasion and underwent tumor resection.One year later, she had a re-recurrent lesion involving her right iliac bone.After one year of chemotherapy, a PET-CT showed no other abdominal lesions suggestive of malignancy.She underwent resection of the re-recurrent tumor involving the right iliac bone and R0 resection was achieved. She was able to ambulate postoperatively and returned home.In selected cases, extended surgery including bone resection can be an option for the local recurrence of advanced colon cancer.
Assuntos
Neoplasias do Colo , Ílio , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Idoso , Colectomia , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Feminino , Humanos , Ílio/patologia , Recidiva Local de NeoplasiaRESUMO
A 77-year-old man underwent a follow-up examination after distal gastrectomy. Contrast-enhanced computed tomography revealed a tumor of the pancreatic body and tail that contacted the common hepatic artery/celiac artery. Subsequently, the tumor was diagnosed as a borderline resectable pancreatic cancer. After chemoradiation therapy, the tumor was considered resectable. Preoperative angiography with intraoperative contrast-enhanced ultrasonography and indocyanine green fluorescence imaging confirmed blood flow in the residual stomach. Postoperatively, ischemic necrosis of the residual stomach was not observed. After distal gastrectomy, distal pancreatectomy with en bloc celiac axis resection was performed to safely and curatively address the cancer of the pancreatic body and tail.
Assuntos
Artéria Celíaca , Gastrectomia , Pancreatectomia , Neoplasias Pancreáticas , Idoso , Quimiorradioterapia , Artéria Hepática , Humanos , Masculino , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgiaRESUMO
A questionnaire survey was conducted on the administration of secondary chemotherapy for unresectable or recurrent gastric cancer by 43 doctors involved in gastric cancer treatment in the Yamaguchi prefecture. Seventy-one percent of doctors replied that the secondary chemotherapy transfer rate was more than 60%, and 29% of doctors replied that the secondary chemotherapy transfer rate was less than 60%. The reasons why patients could not be transferred to secondary chemotherapy included inferior performance status, poor general condition, and elderly age, among others. Weekly paclitaxel plus ramucirumab therapy was used as the major regimen of secondary chemotherapy by 95% of doctors. In addition, 93% of doctors indicated that weekly nab-paclitaxel would be an option for gastric cancer secondary chemotherapy. Secondary chemotherapy for gastric cancer in the Yamaguchi prefecture has a standard regimen selection according to guidelines.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Gástricas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Recidiva Local de Neoplasia , Paclitaxel/uso terapêutico , Padrões de Prática Médica , Neoplasias Gástricas/tratamento farmacológico , Inquéritos e QuestionáriosRESUMO
A 64-year-old man presented with dysphagia. Esophagogastroduodenoscopy revealed a submucosal tumor of 52mm in size at the lower thoracic esophagus. Biopsy yielded a pathological diagnosis of c-kit-positive esophageal gastrointestinal stromal tumor(GIST). We started neoadjuvant therapy with imatinib to avoid excessive surgical invasion. After 6 months of treatment, CT revealed a reduction in tumor size to 27 mm. We performed laparoscopic lower esophagectomy, proximal gastrectomy, double-tract reconstruction, and complete tumor resection. Neoadjuvant imatinib therapy was effective for the esophageal GIST.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Esofágicas , Tumores do Estroma Gastrointestinal , Mesilato de Imatinib/uso terapêutico , Terapia Neoadjuvante , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Cancer stem cells (CSCs) are thought to play important roles in cancer malignancy. Previously, we successfully induced sphere cancer stem-like cells (CSLCs) from several cell lines and observed the property of chemoresistance. In the present study, we examined the metastatic potential of these induced CSLCs. Sphere cancer stem-like cells were induced from a human hepatoma cell line (SK-HEP-1) in a unique medium containing neural survival factor-1. Splenic injection of cells into immune-deficient mice was used to assess hematogenous liver metastasis. Transcriptomic strand-specific RNA-sequencing analysis, quantitative real-time PCR, and flow cytometry were carried out to examine the expression of epithelial-mesenchymal transition (EMT)-related genes. Splenic injection of CSLCs resulted in a significantly increased frequency of liver metastasis compared to parental cancer cells (P < .05). In CSLCs, a mesenchymal marker, Vimentin, and EMT-promoting transcription factors, Snail and Twist1, were upregulated compared to parental cells. Correspondingly, significant enrichment of the molecular signature of the EMT in CSLCs relative to parental cancer cells was shown (q < 0.01) by RNA-sequencing analysis. This analysis also revealed differential expression of CD44 isoforms between CSLCs and parental cancer cells. Increasing CD44 isoforms containing an extra exon were observed, and the standard CD44 isoform decreased in CSLCs compared to parental cells. Interestingly, another CD44 variant isoform encoding a short cytoplasmic tail was also upregulated in CSLCs (11.7-fold). Our induced CSLCs possess an increased liver metastatic potential in which promotion of the EMT and upregulation of CD44 variant isoforms, especially short-tail, were observed.
Assuntos
Carcinoma Hepatocelular/patologia , Transição Epitelial-Mesenquimal/fisiologia , Neoplasias Hepáticas/patologia , Metástase Neoplásica/patologia , Células-Tronco Neoplásicas/patologia , Animais , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Receptores de Hialuronatos/metabolismo , Neoplasias Hepáticas/metabolismo , Camundongos , Células-Tronco Neoplásicas/metabolismo , Fatores de Transcrição/metabolismo , Regulação para Cima/fisiologia , Vimentina/metabolismoRESUMO
BACKGROUND: In this study, cytokine levels, outcome, and survival rates after esophagectomy for esophageal cancer were retrospectively investigated in a propensity score-matched comparison of operative approaches between the thoracoscopic esophagectomy (TE) in the prone position and open esophagectomy (OE). PATIENTS AND METHODS: Between 2005 and 2014, TE was performed on a group of 85 patients, which was compared with a group of 104 OE cases. Eventually, 65 paired cases were matched using propensity score matching. RESULTS: Although the TE group underwent a significantly longer operation time than the OE group (P < 0.001), the TE group exhibited less blood loss (P < 0.001) and had a shorter postoperative hospital stay (P = 0.038) than the OE group. The serum interleukin-6 levels on ICU admission (P < 0.001) and on POD 1 (P < 0.001) were significantly lower in the TE group. The interleukin-10 levels on ICU admission (P < 0.001), POD 1 (P = 0.016), and POD 3 (P < 0.001) were also significantly lower in the TE group. Pulmonary complication was significantly lower in the TE group (P = 0.043). The 5-year PFS rates in the TE and OE groups were 70.6 and 58.7% (P = 0.328), respectively, and OS rates were 64.9 and 50.2% (P = 0.101), respectively. CONCLUSION: TE compared to OE is a less invasive procedure with lower surgical stress and less pulmonary complication for the treatment of esophageal squamous cell carcinoma.
Assuntos
Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Toracoscopia/métodos , Idoso , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Carcinoma de Células Escamosas do Esôfago/mortalidade , Feminino , Humanos , Incidência , Japão/epidemiologia , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Posicionamento do Paciente , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
We report 3 cases of obstructive left-sided colon cancer that could be treated with laparoscopic resection.Case 1: A 25- year-old man was given a diagnosis of colonic obstruction due to transverse colon cancer.Twenty -four days after decompression by a nasointestinal tube, we performed a laparoscopic partial colectomy.Case 2: A 75-year-old woman was given a diagnosis of colonic obstruction due to sigmoid colon.Forty -nine days after decompression by a laparoscopic transverse colostomy, we performed a laparoscopic sigmoidectomy.Case 3: A 48-year-old man was given a diagnosis of colonic obstruction due to sigmoid colon cancer.Twenty -two days after decompression by colonic stent, we performed a laparoscopic sigmoidectomy.In these 3 cases, decompression was sufficient when resecting the primary lesions, and the operations could be completed laparoscopically.Elective radical surgery was possible by resolution of oncologic emergency state.
Assuntos
Neoplasias do Colo/cirurgia , Obstrução Intestinal/cirurgia , Adulto , Idoso , Colectomia , Neoplasias do Colo/complicações , Feminino , Humanos , Obstrução Intestinal/etiologia , Laparoscopia , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Cetuximab has activity against colorectal cancers. Recent studies demonstrated that cetuximab induces antibody-dependent cell-mediated cytotoxicity via immune cells, and a new immune-related mechanism of inducing immunogenic cell death. This study aimed to evaluate the immune responses induced by cetuximab in tumor microenvironments at liver metastasis sites of metastatic colorectal cancer patients. We assessed immune cell infiltration in the liver metastatic sites of 53 colorectal cancer patients. These patients were divided into three groups according to the treatment before operation: chemotherapy with cetuximab, chemotherapy without cetuximab, and no chemotherapy. The inflammatory cells in the liver metastatic sites were assessed by hematoxylin-eosin staining, focusing on the invasive margin. The overall inflammatory reaction and number of lymphoid cells were assessed with a four-point scoring system. We then assessed immune cell infiltration (CD3, CD8 and CD56) in 15 liver metastatic sites. Hematoxylin-eosin staining demonstrated more inflammatory cells in the chemotherapy with cetuximab group than in the other groups (P < 0.001). Of note, inflammatory cells were found in intratumoral areas, and the destruction of cancer cell foci was observed in the chemotherapy with cetuximab group. Moreover, a higher infiltration of CD3+ (P = 0.003), CD8+ (P = 0.003) and CD56+ (P = 0.001) cells was observed in the chemotherapy with cetuximab group than in the other groups. These results suggest that cetuximab might have an immune-enhancing effect. As such, the immune-related mechanism of action of cetuximab may enhance the efficacy of combination therapy, such as chemotherapy and immunotherapy using therapeutic peptides.
Assuntos
Antineoplásicos/uso terapêutico , Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Complexo CD3/metabolismo , Antígeno CD56/metabolismo , Antígenos CD8/metabolismo , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Capecitabina , Neoplasias Colorretais/imunologia , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Feminino , Fluoruracila/análogos & derivados , Fluoruracila/uso terapêutico , Humanos , Inflamação/imunologia , Irinotecano , Leucovorina/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , OxaloacetatosRESUMO
Many clinical trials of peptide vaccines have been conducted. However, these vaccines have provided clinical benefits in only a small fraction of patients. The purpose of the present study was to explore microRNAs (miRNAs) as novel predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer. First, we carried out microarray analysis of pretreatment cancer tissues in a phase I study, in which peptide vaccines alone were given. Candidate miRNAs were selected by comparison of the better prognosis group with the poorer prognosis group. Next, we conducted microarray analysis of cancer tissues in a phase II study, in which peptide vaccines combined with chemotherapy were given. Candidate miRNAs were further selected by a similar comparison of prognosis. Subsequently, we carried out reverse-transcription PCR analysis of phase II cases, separating cancer tissues into cancer cells and stromal tissue using laser capture microdissection. Treatment effect in relation to overall survival (OS) and miRNA expression was analyzed. Three miRNA predictors were negatively associated with OS: miR-125b-1 in cancer cells (P = 0.040), and miR-378a in both cancer cells (P = 0.009) and stromal cells (P < 0.001). Multivariate analysis showed that expression of miR-378a in stromal cells was the best among the three predictors (HR, 2.730; 95% CI, 1.027-7.585; P = 0.044). In conclusion, miR-125b-1 and miR-378a expression might be considered as novel biomarkers to predict the efficacy of vaccine treatment against colorectal cancer.
Assuntos
Vacinas Anticâncer/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MicroRNAs/genética , Animais , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/prevenção & controle , Feminino , Humanos , Microdissecção e Captura a Laser , Masculino , Camundongos , Análise em Microsséries , Prognóstico , Vacinas de Subunidades Antigênicas/administração & dosagemRESUMO
The patient was a 46-year-old woman with left lower abdominal pain.Abdominal dynamic CT revealed a 40 mm, gradually- enhanced pancreatic head mass.The interior of the tumor was heterogeneous and partly low in density.Endoscopic ultrasonography showed a well-defined and heterogeneous tumor with an echoic area in the pancreatic head.Therefore, the cystic lesion with solid components was suspected to be a solid pseudopapillary neoplasm(SPN), considering the age of the patient.Subtotal stomach-preserving pancreaticoduodenectomy was performed.The postoperative course was uneventful, and she was discharged on the 13th day after surgery.Postoperative pathology confirmed a diagnosis of pancreatic acinar cell carcinoma.SPNs often show an image very similar to pancreatic acinar cell carcinoma and it is difficult to distinguish between the two only by imaging findings.Due to the divergence between clinical findings such as age and image findings, it was difficult to confirm a diagnosis of pancreatic acinar cell carcinoma in this case.
Assuntos
Carcinoma de Células Acinares/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma de Células Acinares/tratamento farmacológico , Carcinoma de Células Acinares/cirurgia , Quimioterapia Adjuvante , Combinação de Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Ácido Oxônico/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Tegafur/uso terapêuticoRESUMO
A 50-year-old man with complaints of epigastralgia, pyrexia, and malaise was diagnosed with sigmoid colon cancer, descending colon cancer, and unresectable colorectal liver metastases. Because the prognosticator was liver metastases, he went through chemotherapy(biweekly CapeOX plus cetuximab)as soon as possible. After 6 courses of this regimen, multiple liver metastases were markedly reduced in size(partial response[PR]), resulting in conversion therapy with complete resection. Recently, some reports showed that patients who had R0 resection after conversion chemotherapy could expect favorable long-term prognosis. It is important to select the appropriate first-line chemotherapy and the timing of the conversion resection.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Terapia de Alvo Molecular , Neoplasias do Colo/cirurgia , Terapia Combinada , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
We report 2 cases of laparoscopic simultaneous resection for synchronous liver metastasis of colon cancer. Case 1: A 76- year-old woman was diagnosed with advanced cecum cancer(type 3)with synchronous liver metastasis(segment 5: 23mm), Laparoscopic ileocecal resection and partial liver resection were performed for 414 minutes, with 20 mL of blood loss. The patient was discharged 11 days after the operation. Case 2: A 78-year-old woman was diagnosed with advanced sigmoid colon cancer(type 2)with synchronous liver metastasis(segment 2: 70mm). Laparoscopic sigmoidectomy and extrahepatic resection were performed for 382 minutes, with 10 mL of blood loss. Portal vein thrombus(umbilicus)was recognized but relieved with warfarin. The patient was discharged 15 days after the operation. Simultaneous laparoscopic colon and hepatectomy for synchronous liver metastasis of colorectal cancer can be safely performed for selected indications.