RESUMEN
Hypoxic cellular proliferation is a common feature of tumor cells and is associated with tumor progression. Therefore, the inhibition of hypoxic cellular proliferation is expected to regulate malignancy processes. Licochalcone A (LicA) is known to show inhibitory effects on cell growth in normoxia, but it is unclear whether LicA exerts similar effects in hypoxia. Here, we studied the inhibitory activity of LicA in the hypoxic cellular proliferation of tumor cells and its molecular mechanism using human cell lines derived from various tumors including neuroblastoma and colorectal cancer. LicA inhibited cell growth at a 50% inhibitory concentration between 7.0 and 31.1 µM in hypoxia. LicA significantly suppressed hypoxic induction of tropomyosin receptor kinase B (TrkB) gene expression at the transcription level. LicA also downregulated mRNA levels of the TrkB high-affinity ligand brain-derived neurotrophic factor, but not neurotrophin-4, another TrkB ligand, or glyceraldehyde-3-phosphate dehydrogenase, indicating that the inhibitory activity of LicA is selective. Since both LicA-treatment and TrkB-knockdown decreased activation of protein kinase B in hypoxia, LicA exerts its inhibitory effect against hypoxic cell growth through inhibition of the TrkB-AKT axis. These results suggest that LicA has therapeutic potential for malignant tumors including neuroblastoma and colorectal cancer.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/biosíntesis , Chalconas/farmacología , Neoplasias Colorrectales/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glicoproteínas de Membrana/biosíntesis , Proteínas de Neoplasias/biosíntesis , Neuroblastoma/metabolismo , Receptor trkB/biosíntesis , Hipoxia de la Célula/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Células HeLa , Humanos , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/patologíaRESUMEN
BACKGROUND: Although serum p53 autoantibodies (s-p53-Abs) are induced even in the early stages of colorectal cancer, their positive rate is only approximately 20%. Therefore, we assessed the possibility of using other serum autoantibodies to increase the positive rates for detecting colorectal cancer. METHODS: Autoantibodies against 17 tumor antigens (p53, RalA, HSP70, Galectin1, KM-HN-1, NY-ESO-1, p90, Sui1, HSP40, CyclinB1, HCC-22-5, c-myc, PrxVI, VEGF, HCA25a, p62, and Annexin II) were evaluated in 279 patients with colorectal cancer and 74 healthy controls. Cutoff values were fixed at mean + 3 standard deviations of serum titers in healthy controls. RESULTS: Autoantibodies with the highest positive rates were p53 (20%), RalA (14%), HSP70 (12%), and Galectin1 (11%). Combination assays using multiple autoantibodies increased the positive rates based on the number of autoantibodies used. Positive rates of 56, 62, 66, 71, and 73% were obtained with 6, 9, 11, 14, and 17 antibodies, respectively, for the overall disease. Moreover, these autoantibodies showed relatively high positive rates even during stage 0/I disease (55 and 70% with 6 and 17 antibodies, respectively). CONCLUSION: The measurement of set of 17 autoantibodies allowed autoantibody profiling in patients with colorectal cancer. The combination assay of six tumor antigens (p53, RalA, HSP70, Galectin1, KM-HN-1, and NY-ESO-1) achieved a positive rate of 56%. Such high positive rates will be helpful for detecting colorectal cancer regardless of tumor stages.
Asunto(s)
Antígenos de Neoplasias/sangre , Autoanticuerpos/sangre , Biomarcadores de Tumor/sangre , Neoplasias Colorrectales/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/inmunología , Autoanticuerpos/inmunología , Estudios de Casos y Controles , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Surgical management of malignant bowel obstruction carries with high morbidity and mortality. Placement of a trans-anal decompression tube (TDT) has traditionally been used for malignant bowel obstruction as a bridge to surgery. Recently, colonic metallic stent (CMS) as a bridge to surgery for malignant bowel obstruction, particularly left-sided malignant large bowel obstruction (LMLBO) caused by colorectal cancer, has been reported to be both a safe and feasible option. The aim of this retrospective study is to evaluate the clinical effects of CMS for LMLBO as a bridge to surgery compared to TDT. METHODS: Between January 2000 and December 2015, we retrospectively evaluated outcomes of 59 patients with LMLBO. We compared the outcomes of 26 patients with CMS for LMLBO between 2013 and 2015 (CMS group) with those of 33 patients managed with TDT between 2003 and 2011 (TDT group) by the historical study. LMLBO was defined as a large bowel obstruction due to a colorectal cancer that was diagnosed by computed tomography and required emergent decompression. RESULTS: All patients in the CMS group were successfully decompressed (p = 0.03) and could initiate oral intake after the procedure (p < 0.01). Outcomes in the CMS group were superior to the TDT group in the following areas: duration of tube placement (p < 0.01), surgical approach (p < 0.01), operation time (p < 0.01), number of resected lymph nodes (p < 0.001), and rate of curative resection (p < 0.01). However, no significant differences were found in the overall postoperative complication rate (p = 0.151), surgical site infection rate (p = 0.685), hospital length of stay (p = 0.502), and the need for permanent ostomy (p = 0.745). The 3-year overall survival rate of patients in the CMS and TDT groups was 73.0% and 80.9%, respectively, and this was not significant (p = 0.423). CONCLUSIONS: Treatment with CMS for patients with LMLBO as a bridge to surgery is safe and demonstrated higher rates of resumption of solid food intake and temporary discharge prior to elective surgery compared to TDT. Oncological outcomes during mid-term were equivalent.
Asunto(s)
Canal Anal/cirugía , Neoplasias Colorrectales/complicaciones , Descompresión Quirúrgica/métodos , Procedimientos Quirúrgicos Electivos , Obstrucción Intestinal/terapia , Stents Metálicos Autoexpandibles , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Descompresión Quirúrgica/instrumentación , Femenino , Estudios de Seguimiento , Humanos , Obstrucción Intestinal/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
When a medical provider(medical personnel)becomes a medical receiver(patient), does the consciousness about chemotherapy change ? If yes, what is the main reason ? In this study, we conducted a questionnaire on the consciousness of doctors and pharmacologists engaged in chemotherapy for gastric and/or colorectal cancer. The number of questionnaires collected was 83 and 92 for gastric and colorectal cancer, respectively. In adjuvant chemotherapy, 5%and 4%do not want to receive any chemotherapy for gastric and colorectal cancer if they are patients. The main reasons are binding hours, side effects, and no wish for life extension. About 11%and 9%change their consciousness regarding chemotherapy according to whether they are care providers or receivers. The main reasons are medical perspective and their sense of duty. In chemotherapy for advanced cancer, 6% and 5% of gastric and colorectal cancer patients, do not want to receive any chemotherapy. The main reasons are low expectations for being cured, binding hours, and no wish for life extension. Further, 21%and 14%wish to have limited chemotherapy. As regards consciousness on chemotherapy, 26% and 18% reported changes according to whether they are providers or receivers. The main reasons are medical perspective and their sense of duty. As for the purpose of chemotherapy for advanced gastric and colorectal cancer, 96% and 43% answered prolonging life and relief, respectively. The proportion of persons who answered complete cure is statistically higher in colorectal(32%)than in gastric cancer(18%). The most common answer for an adverse event they want to avoid if they are patients is peripheral neuropathy. These results clearly demonstrate that a considerable proportion of medical personnel hold a negative attitude against or are reluctant to receiving chemotherapy, especially for advanced gastric and colorectal cancer. It is of great importance to make use of these results in clinical practice.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Personal de Salud , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Antineoplásicos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Encuestas y CuestionariosRESUMEN
BACKGROUND & AIMS: Molecular events that lead to recurrence and/or metastasis after curative treatment of patients with colorectal cancers (CRCs) are poorly understood. Patients with stage II or III primary CRC with elevated microsatellite alterations at selected tetranucleotide repeats and low levels of microsatellite instability (E/L) are more likely to have disease recurrence after treatment. Hypoxia and/or inflammation not only promote metastasis, but also induce elevated microsatellite alterations at selected tetranucleotide repeats by causing deficiency of MSH3 in the cancer cell nucleus. We aimed to identify genetic alterations associated with metastasis of primary colorectal tumors to liver and to determine their effects on survival. METHODS: We obtained 4 sets of primary colorectal tumors and matched liver metastases from hospitals in Korea and Japan. Intragenic microsatellites with large repeats at 141 loci were examined for frame-shift mutations and/or loss of heterozygosity (LOH) as possible consequences of MSH3 deficiency. Highly altered loci were examined for association with E/L in liver metastases. We analyzed data from 156 of the patients with stage II or III primary colorectal tumors to determine outcomes and whether altered loci were associated with E/L. RESULTS: LOH at several loci at chromosome 9p24.2 (9p24.2-LOH) was associated with E/L in liver metastases (odds ratio = 10.5; 95% confidence interval: 2.69-40.80; P = .0007). We found no significant difference in the frequency of E/L, 9p24.2-LOH, mutations in KRAS or BRAF, or the combination of E/L and 9p24.2-LOH, between primary colorectal tumors and their matched metastases. Patients with stage II or III colorectal tumors with E/L and 9p24.2-LOH had increased survival after CRC recurrence (hazard ratio = 0.25; 95% CI: 0.12-0.50; P = .0001), compared with patients without with E/L and 9p24.2-LOH. E/L with 9p24.2-LOH appeared to be an independent prognostic factor for overall survival of patients with stage III CRC (hazard ratio = 0.06; 95% CI: 0.01-0.57; P = .01). CONCLUSIONS: E/L with 9p24-LOH appears to be a biomarker for less aggressive metastasis from stage III primary colorectal tumors.
Asunto(s)
Biomarcadores de Tumor/genética , Aberraciones Cromosómicas , Cromosomas Humanos Par 9 , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundario , Pérdida de Heterocigocidad , Repeticiones de Microsatélite , Distribución de Chi-Cuadrado , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/cirugía , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Predisposición Genética a la Enfermedad , Humanos , Japón , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Modelos Logísticos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Oportunidad Relativa , Fenotipo , Modelos de Riesgos Proporcionales , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , República de Corea , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Fournier's gangrene in the setting of rectal cancer is rare. Treatment for Fournier's gangrene associated with rectal cancer is more complex than other cases of Fournier's gangrene. We report on a patient with severe Fournier's gangrene in the setting of locally advanced rectal cancer who was treated with a combined modality therapy. CASE PRESENTATION: A 65-year-old man presented with general fatigue and anal pain. The medical and surgical histories were unremarkable. A black spot on the perineal skin surrounded by erythema was found on physical examination, suspicious for Fournier's gangrene. Computed tomography scan showed a rectal tumor invading into the bladder (clinically T4bN2M0) and abscess formation with emphysema around the rectum. He was thus diagnosed with locally advanced rectal cancer and Fournier's gangrene with a severity index score of 12 points. We created a diverting loop colostomy of the transverse colon and performed extensive debridement of the perineum and perianal area. Fifty days later, the patient underwent radical total pelvic exenteration with sacrectomy. In addition, reconstruction of the soft tissue defect was performed using the rectus muscle, the gluteus maximus muscle, and the femoral muscle. Histopathological findings of the specimen were as follows: the tumor was a moderately adenocarcinoma with invasion to the bladder and the prostate (T4b), metastases to four resected lymph nodes (N2), and lymphovascular invasion. There were no major postoperative complications, and the patient was discharged 108 days postoperatively. CONCLUSIONS: We report a rare case of locally invasive rectal cancer associated with Fournier's gangrene. This case highlights a usual cause of Fournier's gangrene. Physicians should be cognizant not only of the more common condition but also of the rare presentations including those associated with rectal cancer.
Asunto(s)
Gangrena de Fournier/patología , Neoplasias del Recto/patología , Anciano , Gangrena de Fournier/complicaciones , Gangrena de Fournier/cirugía , Humanos , Masculino , Pronóstico , Neoplasias del Recto/complicaciones , Neoplasias del Recto/cirugíaRESUMEN
We report a case of aortoesophageal fistula rupture during the course of chemotherapy following colon cancer resection. The patient was a 77-year-old woman. Following recurrence of cancer of the sigmoid colon, the patient received a course of XELOX plus bevacizumab(Bmab)to treat peritoneal dissemination and lung metastases. She was brought by ambulance to our hospital's emergency department 55 days after the last dose of Bmab, with a chief complaint of hematemesis. Hematolo- gy results showed severe anemia with a hemoglobin level of 4.0 g/dL. Descending thoracic aortic dissection was noted on chest CT with contrast, and the patient was diagnosed with an aortoesophageal fistula rupture. She underwent emergent endovascular chest stent grafting to control the bleeding. Although the ruptured esophagus was a potential source of infection, the patient and family members chose palliative treatment. Therefore, conservative treatment was administered without removing the esophagus. The patient's postoperative course was good; instead of resuming oral intake, the patient was discharged on home IVH 59 days after surgery. Outpatient follow-up continued, but multiple metastases led to gradual worsening of the patient's general condition. She died 168 days after being admitted for surgery.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedades de la Aorta/cirugía , Bevacizumab/efectos adversos , Neoplasias del Colon/tratamiento farmacológico , Fístula Esofágica/cirugía , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Enfermedades de la Aorta/etiología , Bevacizumab/administración & dosificación , Capecitabina , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Fístula Esofágica/etiología , Resultado Fatal , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Oxaloacetatos , Complicaciones Posoperatorias , RecurrenciaRESUMEN
BACKGROUND/AIMS: A phase I study was performed to evaluate the dose-limiting toxicity and the recommended dose of the oral fluoropyrimidine S-1 when administered concurrently with radiation therapy to 9 Japanese patients with low rectal cancer. METHODOLOGY: S-1 was given orally for a total of 9 weeks (4 weeks alone and 5 weeks during radiation therapy) at oral doses of 65 mg/m2/day (n = 3 patients) or 80 mg/m2/day (n = 6 patients). Radiation therapy was administered in 1.5 gray fractions five times weekly (Monday to Friday) for a total dose of 45 gray. RESULTS: All patients achieved the planned 45 gray of radiation therapy. There was no grade > or = 3 toxicity. The recommended dose of S-1 was determined to be 80 mg/m2/ day. The dose intensity of S-1 was well maintained, and the combination of S-1 plus radiation therapy was well tolerated by all patients. Sphincter-preserving procedures were possible in all but one (89%) patient. High rates of tumor shrinkage and nodular downstaging were achieved. The histological response rate was 78%, including one complete response. CONCLUSIONS: The recommended dose of S-1 with concurrent radiation therapy was 80 mg/m2/day. Pre-operative chemoradiation therapy with S-1 was feasible and well tolerated by patients with low rectal cancer.
Asunto(s)
Adenocarcinoma/terapia , Antimetabolitos Antineoplásicos/uso terapéutico , Quimioradioterapia , Ácido Oxónico/uso terapéutico , Neoplasias del Recto/terapia , Tegafur/uso terapéutico , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Administración Oral , Adulto , Anciano , Terapia Combinada , Fraccionamiento de la Dosis de Radiación , Combinación de Medicamentos , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: KRAS mutation is an important prognostic factor for patients with metastatic colorectal cancer receiving anti-epidermal growth factor receptor therapy. However, the influence of KRAS mutation on the response to mFOLFOX6 ± bevacizumab remains unclear. METHODOLOGY: We retrospectively analyzed 49 patients who received modified FOLFOX6 (mFOLFOX6) ± bevacizumab as first-line therapy. Genetic analysis showed that 30 patients had wild-type (WT) KRAS and 19 patients hadKRAS mutations (MT). These two groups were compared with regard to the response rate (RR), progression-free survival (PFS), and overall survival (OS). RESULTS: The RR was not significantly different between the WT and MT groups, but PFS and OS were significantly better in the WT group than the MT group (PFS: 11.8 months vs. 8.7 months, p<0.01; OS: 37.8 months vs. 29.3 months, p<0.0385). A similar analysis of 27 patients who were treated with mFOLFOX6 + bevacizumab showed a better prognosis for WT patients. Multivariate analysis also revealed that KRAS mutation was an independent factor with a significant relation to PFS. CONCLUSIONS: These results suggest that KRAS mutation may be a useful prognostic marker for patients with metastatic colorectal cancer receiving mFOLFOX6 ± bevacizumab therapy, especially for patients treated with mFOLFOX6 + bevacizumab.
Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Mutación , Proteínas Proto-Oncogénicas/genética , Proteínas ras/genética , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Femenino , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Compuestos Organoplatinos/administración & dosificación , Proteínas Proto-Oncogénicas p21(ras) , Estudios RetrospectivosRESUMEN
BACKGROUND/AIMS: In Japan lateral pelvic lymph node dissection has been actively performed with total mesorectal excision for low rectal cancer. However, its definitive efficacy remains unclear. This study is to evaluate clinical significance of lateral pelvic lymphatic drainage in low rectal cancer patients by 99mTc-Sn colloid radioactive tracers. METHODOLOGY: Intraoperatively detecting rectal lymphatic drainage using 99mTc-Sn colloid radioactive tracer in 39 low rectal cancer patients, we performed lateral pelvic lymph node dissection in lateral pelvic lymphatic flow-positive patients. RESULTS: Lateral pelvic lymphatic flow was detected in 11 patients (28%). In four (36%) of 11 patients, tumor cells were histologically identified in lateral pelvic lymph nodes. A median size of metastatic lateral pelvic lymph nodes was 7.5 (range, 2-150) mm, and all but one overlooked patient could not be detected by routine preoperative imaging scans retrospectively. The five-year disease-free survival rate of lateral pelvic lymphatic flow-positive patients was significantly poorer (45% vs. 75%, p = 0.0044). CONCLUSIONS: Tumor cells potentially extended beyond the fascia propria recti in low rectal cancer with lateral pelvic lymphatic flow. Preoperative chemoradiation therapy and adjuvant therapy are considered to be reasonable to improve a poor prognosis of low rectal cancer patients with lateral pelvic lymphatic flow.
Asunto(s)
Neoplasias del Recto/patología , Adulto , Anciano , Drenaje , Femenino , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Persona de Mediana Edad , Pelvis/patología , Tomografía de Emisión de Positrones , Neoplasias del Recto/mortalidad , Neoplasias del Recto/terapiaRESUMEN
PURPOSE: Although the definitive risk factors for parastomal hernia development remain unclear, potential contributing factors have been reported from Western countries. The aim of this study was to identify the risk factors for parastomal hernia in Japanese patients with permanent colostomies. METHODS: All patients who received abdominoperineal resection or total pelvic exenteration at our institution between December 2004 and December 2011 were reviewed. Patient-related, operation-related and postoperative variables were evaluated, in both univariate and multivariate analyses, to identify the risk factors for parastomal hernia formation. RESULTS: Of the 80 patients who underwent colostomy, 22 (27.5 %) developed a parastomal hernia during a median follow-up period of 953 days (range 15-2792 days). Hernia development was significantly associated with increasing patient age and body mass index, a laparoscopic surgical approach and the transperitoneal route of colostomy formation. In the multivariate analysis, the body mass index (p = 0.022), the laparoscopic approach (p = 0.043) and transperitoneal stoma creation (p = 0.021) retained statistical significance. CONCLUSIONS: Our findings in Japanese ostomates match those from Western countries: a higher body mass index, the use of a laparoscopic approach and a transperitoneal colostomy are significant independent risk factors for parastomal hernia formation. The precise role of the stoma creation route remains unclear.
Asunto(s)
Colostomía/efectos adversos , Colostomía/métodos , Hernia Ventral/etiología , Estomas Quirúrgicos/efectos adversos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Índice de Masa Corporal , Femenino , Estudios de Seguimiento , Hernia Ventral/epidemiología , Humanos , Laparoscopía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
Management of nutrition in cancer patients plays an important role in supporting anti-cancer treatment. Parenteral nutrition is considered to assist with nutrition in cancer patients. Central venous catheters(CVC)are useful for intravenous infusion of not only nutrients with high osmotic pressure but also chemotherapeutic drugs and other substances. Central venous access through CV ports reduces patient's burden and complications, and it contributes to maintaining a patient's quality of life(QOL).
Asunto(s)
Cateterismo Venoso Central , Catéteres de Permanencia , Nutrición Parenteral Total , Humanos , Calidad de VidaRESUMEN
OBJECTIVE: Distant metastasis is the major cause of cancer-related death in patients with colorectal cancer (CRC). Although the microRNA-200 (miR-200) family is a crucial inhibitor of epithelial-to-mesenchymal transition (EMT) in human cancer, the role of miR-200 members in the pathogenesis of metastatic CRC has not been investigated. DESIGN: Fifty-four pairs of primary CRC and corresponding matched liver metastasis tissue specimens were analysed for expression and methylation status of the miR-200 family members. Functional analysis of miR-200c overexpression was investigated in CRC cell lines, and cells were analysed for proliferation, invasion and migration. Expression of several miR-200c target genes (ZEB1, ETS1 and FLT1) and EMT markers (E-cadherin and vimentin) in CRC cell lines and tissue specimens was validated. RESULTS: Liver metastasis tissues showed higher expression of miR-200c (primary CRC = 1.31 vs. liver metastasis = 1.59; p = 0.0014) and miR-141 (primary CRC = 0.14 vs. liver metastasis = 0.17; p = 0.0234) than did primary CRCs, which was significantly associated with hypomethylation of the promoter region of these miRNAs (primary CRC = 61.2% vs. liver metastasis = 46.7%; p < 0.0001). The invasive front in primary CRC tissues revealed low miR-200c expression by in situ hybridization analysis. Transfection of miR-200c precursors resulted in enhanced cell proliferation but reduced invasion and migration behaviours in CRC cell lines. Overexpression of miR-200c in CRC cell lines caused reduced expression of putative gene targets, and resulted in increased E-cadherin and reduced vimentin expression. The associations between miR-200c, target genes and EMT markers were validated in primary CRCs and matching liver metastasis tissues. CONCLUSIONS: miR-200c plays an important role in mediating EMT and metastatic behaviour in the colon. Its expression is epigenetically regulated, and miR-200c may serve as a potential diagnostic marker and therapeutic target for patients with CRC.
Asunto(s)
Cadherinas/metabolismo , Neoplasias Colorrectales , Transición Epitelial-Mesenquimal/genética , MicroARNs/genética , Vimentina/metabolismo , Anciano , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral/metabolismo , Proliferación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/secundario , Masculino , Metilación , Persona de Mediana Edad , Estadificación de Neoplasias , Transfección/métodosRESUMEN
Down-regulation of hMSH3 is associated with elevated microsatellite alterations at selected tetranucleotide repeats and low levels of microsatellite instability in colorectal cancer (CRC). However, the mechanism that down-regulates hMSH3 in CRC is not known. In this study, a significant association between over-expression of glucose transporter 1, a marker for hypoxia, and down-regulation of hMSH3 in CRC tissues was observed. Therefore, we examined the effect of hypoxia on the expression of hMSH3 in human cell lines. When cells with wild type p53 (wt-p53) were exposed to hypoxia, rapid down-regulation of both hMSH2 and hMSH3 occurred. In contrast, when null or mutated p53 (null/mut-p53) cells were exposed to hypoxia, only hMSH3 was down-regulated, and at slower rate than wt-p53 cells. Using a reporter assay, we found that disruption of the two putative hypoxia response elements (HREs) located within the promoter region of the hMSH3 abrogated the suppressive effect of hypoxia on reporter activity regardless of p53 status. In an EMSA, two different forms of HIF-1α complexes that specifically bind to these HREs were detected. A larger complex containing HIF-1α predominantly bound to the HREs in hypoxic null/mut-p53 cells whereas a smaller complex predominated in wt-p53 cells. Finally, HIF-1α knockdown by siRNA significantly inhibited down-regulation of hMSH3 by hypoxia in both wt-p53 and mut-p53 cells. Taken together, our results suggest that the binding of HIF-1α complexes to HRE sites is necessary for down-regulation of hMSH3 in both wt-p53 and mut-p53 cells.
Asunto(s)
Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Proteínas de Unión al ADN/genética , Regulación hacia Abajo/genética , Secuencia de Bases , Hipoxia de la Célula/genética , Línea Celular Tumoral , Proteínas de Unión al ADN/metabolismo , Regulación Neoplásica de la Expresión Génica , Genes Reporteros , Transportador de Glucosa de Tipo 1/metabolismo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Datos de Secuencia Molecular , Proteína 3 Homóloga de MutS , Regiones Promotoras Genéticas/genética , Unión Proteica/genética , Elementos de Respuesta/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
A 74-year-old woman was diagnosed with advanced rectal cancer and stenosis. To resolve the rectal stenosis, we successfully placed an expandable metallic stent across the stenosis. After stent placement, food intake improved, and a good quality of life was maintained. Subsequently, the patient received systemic chemotherapy with modified FOLFOX6 (mFOLFOX6). The tumor responded remarkably to chemotherapy, and the patient did not experience any complications. After 2 courses of mFOLFOX6, the patient underwent high anterior resection. The postoperative course was satisfactory, and she has now been disease-free for 6 months after surgery.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Obstrucción Intestinal/terapia , Terapia Neoadyuvante , Stents , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Colon/complicaciones , Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Femenino , Fluorouracilo/administración & dosificación , Humanos , Obstrucción Intestinal/etiología , Leucovorina/administración & dosificación , Estadificación de Neoplasias , Compuestos Organoplatinos/administración & dosificaciónRESUMEN
A 36-year-old woman visited our hospital with a chief complaint of bleeding during defecation. Colonoscopy revealed a 20-mm pedunculated polyp in the sigmoid colon, which was en bloc resected under endoscopy. The histopathological diagnosis was adenoma cancer with a depth of invasion indicating mucosal cancer, no lymphovascular invasion, and negative at the resection margin. The poorly differentiated adenocarcinoma component comprised approximately 5% of the tumor. Although there were no recurrence signs in the computed tomography scans obtained 4 months post polypectomy, the patient experienced aggressive lower back pain at 6 months post polypectomy. Local recurrence, peritoneal dissemination, and liver metastasis were confirmed. Finally, the patient died following a rapid and aggressive deterioration of her general condition. Histological examination of the local recurrence revealed a poorly differentiated adenocarcinoma (por2), with immunostaining revealing a high Ki67 positivity rate of 95%. Moreover, the poorly differentiated adenocarcinoma region of the resected polyp had a Ki67 positivity rate of 90%, which suggested that they were the same tumors. These findings suggested that the recurrence could have occurred through implantation.
RESUMEN
Pelvic organ prolapse (POP) is a condition wherein one or more of the organs in the pelvis slip down from their original position and protrude into the vagina. Pelvic organ prolapse surgery has increased in the urogynecological field due to higher aging society. POP patients often suffer from bowel dysfunction, such as difficulty of bowel movements and the need to strain or push on the vagina to have a bowel movement. Rectocele is often treated with the same method used for POP, but sometimes it is treated transanally. In the transabdominal approach, the vagina is divided from the rectum, and the mesh is fixed between the vagina and rectum. On the other hand, rectal prolapse is a condition wherein the rectum slips down from its original position and protrudes from the anus. Like POP surgery, rectal prolapse has been treated laparoscopically. Even though the protruding position is different, both are pelvic conditions, and the concept of treatment is similar. Recently, POP and rectal prolapse have been diagnosed at the same time, and sometimes these diseases have been treated together. In the higher aging society, incidences of POP and rectal prolapse will increase, and both will have greater chance to be treated. Although POP is a urogynecological disease, coloproctologists need to know the bowel dysfunction in order to treat POP.
RESUMEN
UNLABELLED: We report 5 cases of colorectal liver metastases (CRLM) with hepatic arterial infusion (HAI) oxaliplatin after systemic infusion chemotherapy failure. Patients with unresectable CRLM and history of systemic chemotherapy failure were treated with HAI oxaliplatin (L-OHP 100 mg/body, 2 hours) combined with intravenous (iv) levofolinate calcium (175 mg/body, 2 hours) and iv bolus 5-FU (500 mg/body) every 2 weeks. RESULT: An average age was 58 years. All patients had previously received FOLFOX. Lung metastases had already existence before HAI oxaliplatin in 4 patients. A median of 10 treatments were administered (range 5-14). Serum level of CEA was decreased in 4 cases. In 2 patients, lung metastasis developed while a PR was obtained in the liver metastasis. Progress disease (PD) was confirmed in other 3 patients. No major toxicity was presented. The median time to progression free survival was 3.0 months and the median overall survival was 7.1 months. CONCLUSION: HAI oxaliplatin might be beneficial as a salvage therapy for CRLM without extrahepatic metastasis, which demonstrated an acceptable tolerability and maintenance of QOL.
Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Compuestos Organoplatinos/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Resistencia a Antineoplásicos , Femenino , Fluorouracilo/uso terapéutico , Arteria Hepática , Humanos , Infusiones Intraarteriales , Infusiones Parenterales , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/uso terapéutico , Oxaliplatino , Estudios Retrospectivos , Terapia RecuperativaRESUMEN
We experienced a case in which the hepatic artery catheter system could be used long term. Even after 5 years and five months, there was no damage to the hepatic artery, and we could still use this system. For insertion of the catheter, a fine catheter with the tip tapered at 2.7 F was selected. This catheter was inserted into the hepatic artery peripheral branch in the liver, after a side hole was created 11 cm from the tip, and the side hole was adjusted to stay in the common hepatic artery. We speculated that the reason for little injury to the hepatic artery was use of a fine catheter despite possible damage to the hepatic artery wall like saw cutting in this case. We classified the patterns according to which a catheter damaged the inner wall of the hepatic artery into 5: "straight punch type", "hook punch type", "whiplash type", "elbow blow type", "and saw type".
Asunto(s)
Cateterismo , Arteria Hepática , Infusiones Intraarteriales , Arteria Hepática/patología , Humanos , Infusiones Intraarteriales/instrumentación , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
OBJECTIVES: Palliative stoma creation should be considered in patients at high risk of colonic metallic stent failure. However, it is unclear whether ileostomy or colostomy is superior. This study compared short-term outcomes between palliative ileostomy and colostomy. METHODS: We identified 82 patients with malignant large bowel obstruction, caused by various advanced cancers, between January 2005 and December 2016. We compared short-term outcomes between the ileostomy group (n = 33) and the colostomy group (n = 49). RESULTS: For all 82 patients, clinical success was achieved. Three patients with ileostomy died within 30 days of ostomy formation. The ileostomy group had statistically significant differences in median operative time (113 vs. 129 minutes, p = 0.045) and blood loss (8 vs. 40 g, p = 0.037) in comparison with the colostomy group. No statistically significant differences were observed in the surgical complications (30.3 vs. 38.8%, p = 0.431), in the median period to oral intake (3 vs. 4 days, p = 0.335) and in the hospital stay after surgery (32 vs. 27 days, p = 0.509) between the two groups. Overall stoma-related complications occurred in 27 (32.9%) patients. Stoma-related complications occurred more frequently in the ileostomy group (16/33 vs. 11/49 patients, p = 0.014). High output stoma (6 patients) and irritation (5 patients) occurred more frequently in the ileostomy group. CONCLUSIONS: Palliative colostomy is superior to ileostomy due to fewer stoma-related complications. When ileostomy is required, aggressive interventions for high output stomas should be implemented.