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1.
Pathol Int ; 70(2): 92-100, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31867815

RESUMEN

The clinicopathological significance of carbohydrate antigen 19-9 (CA19-9) in gastric cancer (GC) remains obscure. Therefore, the current study aimed to clarify the clinicopathological value of CA19-9 in GC utilizing autopsy cases. We examined the expression of CA19-9 and mucin core proteins in GC immunohistochemically, and analyzed serum CA19-9 levels and clinicopathological variables or complications. We also investigated whether fucosyltransferases 2 and 3 (FUT2/3) allelic variants influence CA19-9 expression in GC. Compared to GC cases with negative CA19-9 expression (tCA19-9-N), those with positive CA19-9 expression (tCA19-9-P) demonstrated significant differences in characteristic features such as lymph node and distant organ metastases, lymphatic and venous permeation, and higher Tumor, Node, Metastasis (TNM) stages. Moreover, compared to GC cases with low serum CA19-9 levels (sCA19-9-L), those with high serum CA19-9 levels (sCA19-9-H) were related to venous permeation, higher proportion of lymph node and distant organ metastases, and higher TNM stages. Both tCA19-9-P GC and sCA19-9-H GC cases were significantly associated with coagulation abnormalities. sCA19-9-H GC cases correlated significantly with MUC1 and MUC5AC expression. FUT2/3 genotypes were not associated with CA19-9 expression in GC. These results suggest that CA19-9 can predict the risk of lymph node and distant metastases as well as of coagulation abnormalities.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Antígeno CA-19-9/biosíntesis , Neoplasias Gástricas/patología , Anciano , Anciano de 80 o más Años , Autopsia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico
2.
Tumour Biol ; 39(4): 1010428317698393, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28443499

RESUMEN

Partitioning defective 3-like protein is a novel cell polarity protein. Recently, partitioning defective 3-like protein has been demonstrated with tumor-promoting function by disrupting tight junction, inhibiting tumor suppressor liver kinase B1, and maintaining mammary stem cells. For the first time, we studied partitioning defective 3-like protein expression in malignant colorectal cancer. We used immunohistochemistry scoring system to evaluate partitioning defective 3-like protein expression in 196 colorectal cancer tissues and 33 adjacent normal tissues. We found that colorectal cancer tissues had much stronger partitioning defective 3-like protein immunoreactivity than normal tissues, and colorectal cancer patients with positive partitioning defective 3-like protein expression were characterized with higher cancer stages, metastasis, poor tumor differentiation, larger tumor size, as well as high levels of colorectal cancer markers carcinoembryonic antigen and cancer antigen 19-9. Besides, partitioning defective 3-like protein overexpression was independently predictive of lower survival rate in colorectal cancer patients, even after adjusting the influence of cofactors. Moreover, we also found that partitioning defective 3-like protein was associated with rapid growing colorectal cancer, while knockdown of partitioning defective 3-like protein expression largely inhibited cancer cell proliferation. Our study provided the first evidence that partitioning defective 3-like protein was overexpressed in colorectal cancer and associated with disease malignancy. Also, partitioning defective 3-like protein may serve as a promising prognostic marker and a potential therapeutic target for colorectal cancer treatment. Further study is necessary to understand the regulatory mechanism of partitioning defective 3-like protein in colorectal cancer and the feasibility of its application in clinic.


Asunto(s)
Biomarcadores de Tumor/biosíntesis , Proteínas Portadoras/biosíntesis , Proliferación Celular/genética , Neoplasias Colorrectales/genética , Proteínas de la Membrana/biosíntesis , Anciano , Biomarcadores de Tumor/genética , Antígeno CA-19-9/biosíntesis , Antígeno Carcinoembrionario/biosíntesis , Proteínas Portadoras/genética , Polaridad Celular/genética , Neoplasias Colorrectales/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Pronóstico
3.
Pancreatology ; 16(6): 1057-1062, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27692554

RESUMEN

BACKGROUND: Carbohydrate antigen 19-9 (CA19-9) is currently the most widely used biomarker for pancreatic cancer. It is well-known that Lewis and Secretor status can affect CA19-9 biosynthesis. This study was performed to optimize CA19-9 in detecting pancreatic cancer using Lewis and Secretor dependent cut-off values. METHODS: Lewis and Secretor genotypes were determined by Sanger sequencing in a large cohort of subjects (578 cases with pancreatic cancer, 210 cases with benign pancreatic disease, 315 normal subjects). The effectiveness of CA19-9 for detecting pancreatic cancer using Lewis and Secretor group dependent cut-off values was evaluated. RESULTS: The Lewis (-), Mixed, and Secretor (-) groups had low, medium, and high CA19-9 biosynthesis, respectively. In Lewis (-) pancreatic cancer (all stages), CA19-9 had a sensitivity of 48.6% and a specificity of 95.9% when 1.8 U/mL was used as the cut-off value. The sensitivity of CA19-9 in detecting all stages of pancreatic cancer improved from 80.1% to 88.0% and the negative predictive value increased from 81.2% to 87.1% without compromising other values when using group dependent cut-off values. The sensitivity of CA19-9 for the detection of stage I, II pancreatic cancer increased from 76.1% to 87.2%. CONCLUSIONS: The value of CA19-9 in detecting pancreatic cancer was optimized by using group dependent cut-off values based on Lewis and Secretor genotypes. CA19-9 can be applied as an early detector of pancreatic cancer using group dependent cut-off values.


Asunto(s)
Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Antígeno CA-19-9/sangre , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Biomarcadores de Tumor , Antígeno CA-19-9/biosíntesis , Estudios de Cohortes , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Enfermedades Pancreáticas/diagnóstico , Enfermedades Pancreáticas/genética , Valor Predictivo de las Pruebas
4.
Gan To Kagaku Ryoho ; 43(12): 1963-1965, 2016 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-28133190

RESUMEN

Trousseau's syndrome is a coagulation disorder occurring in cancer patients. In the present study, we report our experience regarding the pathophysiology and treatment strategies of this syndrome that is caused by CA19-9-producing gastric cancer during long term chemotherapy. A 60s male presented to our clinic; he was found to have a high level of CA19-9. An advanced gastric cancer was identified by gastric scope. A totalgastrectomy was performed. Severalcourses of chemotherapy were administered, and the level of CA19-9 was measured over a long period. Three years and 2 months after the surgery, he presented to the emergency room complaining of acute onset of aphasia and paresis of the extremities. Brain MRI showed multiple cerebral infarctions. He was diagnosed with Trousseau's syndrome. Although decision making is difficult in the treatment of this syndrome, owing to the complex medicalhistory associated with it, it is essentialthat strategies be established for achieving successfultreatment results in the future.


Asunto(s)
Trastornos de la Coagulación Sanguínea/etiología , Antígeno CA-19-9/biosíntesis , Neoplasias Gástricas/complicaciones , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado Fatal , Humanos , Masculino , Neoplasias Gástricas/química , Neoplasias Gástricas/tratamiento farmacológico , Síndrome
5.
Gan To Kagaku Ryoho ; 43(7): 885-7, 2016 Jul.
Artículo en Japonés | MEDLINE | ID: mdl-27431634

RESUMEN

The patient, a man in his 60s, visited his physician with hemosputum. The shadow of a large mass, measuring approximately 6 cm in diameter, was observed in the left upper lung field, and the patient was referred to our hospital. After thorough examination, the mass was diagnosed as a pulmonary adenocarcinoma. In addition, serum CA19-9 levels were elevated(608.9 U/mL). Based on the PET-CT scan, the cancer was diagnosed as cT2bN1M0, stage II B disease and surgery was performed. The thorax was opened via a posterolateral incision; left upper lobectomy and lymph node dissection(ND2a-2)were performed. The lesion, measuring 56×59×44 mm, was excised from S1+2. The histopathological diagnosis was poorly-differentiated adenocarcinoma(mucin-producing adenocarcinoma). On immunostaining, the lesion was CA19-9-positive and was confirmed as pT2bN1M0, stage II B disease. The serum CA19-9 level was still elevated after surgery(83.2 U/mL). Therefore, 6 courses of adjuvant chemotherapy(carboplatin plus weekly paclitaxel)were administered. Grade 2 adverse events included hair loss and neutropenia. Thus, the drug withdrawal period was extended. After completion of 2 courses of the therapy, the serum CA19-9 level normalized. Two years after surgery, there has been no sign of recurrence.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno CA-19-9/biosíntesis , Neoplasias Pulmonares/tratamiento farmacológico , Adenocarcinoma/química , Adenocarcinoma/metabolismo , Adenocarcinoma/cirugía , Adenocarcinoma del Pulmón , Antígeno CA-19-9/análisis , Carboplatino/administración & dosificación , Quimioterapia Adyuvante , Humanos , Neoplasias Pulmonares/química , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirugía , Escisión del Ganglio Linfático , Masculino , Neutropenia , Paclitaxel/administración & dosificación
6.
Surg Today ; 44(11): 2157-61, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24407283

RESUMEN

Measuring tumor marker levels following cancer treatment can be useful. Although serum thyroglobulin is a useful marker after total thyroidectomy for papillary thyroid carcinoma (PTC), it is not a reliable marker for patients with a high titer of anti-thyroglobulin antibodies or when transformation to undifferentiated carcinoma has occurred. The female patient in this case report underwent total thyroidectomy and oral I-131 therapy for PTC at the age of 47 years, followed by cervical lymph node and lung resections for metastases, 3 and 11 years later, respectively. She also received oral I-131 therapy and external beam radiotherapy for mediastinal lymph node metastases. The lymphadenopathy lesions progressed and multiple lung metastases were detected when she was 61 years of age. She died at the age of 62 years. The serum CA19-9 level had gradually increased in association with enlargement of the recurrent lesions and immunostaining of CA19-9 in the pulmonary metastasis was intense. Thus, we consider that measuring the level of serum CA19-9 is an effective tool for evaluating disease status after surgery for PTC.


Asunto(s)
Antígeno CA-19-9/biosíntesis , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/secundario , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundario , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/sangre , Antígeno CA-19-9/análisis , Antígeno CA-19-9/sangre , Carcinoma Papilar/metabolismo , Resultado Fatal , Femenino , Humanos , Radioisótopos de Yodo/uso terapéutico , Neoplasias Pulmonares/metabolismo , Escisión del Ganglio Linfático , Metástasis Linfática , Mediastino , Persona de Mediana Edad , Radiofármacos/uso terapéutico , Tiroidectomía
7.
Tumour Biol ; 33(2): 463-74, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22161237

RESUMEN

Cancer may be diagnosed in advanced stages, when the patient has already developed metastasis, with symptoms that can be also observed in benign diseases. The objective of this study was to evaluate tumor marker sensitivity and specificity in the differential diagnosis of patients with suspected signs of cancer. We studied 2.711 consecutive patients admitted to the Internal Medicine Department of our hospital with suspected cancer; 1.240 patients had non-malignant processes and 1.471 had malignant disease. Determinations were considered positive for suspected malignancy when serum levels were carcinoembryonic antigen >15 ng/ml (>20 in patients with renal failure or liver disease), alpha fetoprotein >40 ng/ml (>80 ng/ml in patients with liver diseases), carbohydrate antigen (CA) 19.9 > 200 U/ml (>500 U/ml in patients with liver diseases or gamma glutamyl transpeptidase (GGT) <150 UI/L or effusions; >1.000 U/ml in patients with jaundice or GGT > 150 UI/L), neuron-specific enolase >45 ng/ml (renal failure >50 ng/ml; samples with hemolysis were excluded), prostate-specific antigen > 30 ng/ml (excluding acute prostatitis), tumor-associated glycoprotein-72 >80 U/ml, cytokeratin 19 fragment 21-1 > 7.5 ng/ml (>19 ng/ml in patients with renal failure; >11 ng/ml in patients with liver cirrhosis or jaundice), >3.5 ng/ml for squamous cell carcinoma (excluding patients with renal failure or skin disorders), CA 15.3 >100 U/ml, and CA 125 >350 U/ml (>600 U/ml in patients with pleural effusion and >900 U/ml in those with ascites). There was a specificity of 97.6% in patients without malignancy, 67.4% of sensitivity in patients with malignancy, and 75.4% of sensitivity in the 1,280 patients with epithelial tumors (53.7% in patients with locally advanced tumors and 79.4% in patients with metastases). Sensitivity was 81.4% in patients with cancer of unknown primary site. Tumor markers were useful in the differential diagnosis between epithelial and non-epithelial tumors, brain masses (metastases vs. primary tumors), and between benign or malignant origin of different clinical situations such as wasting syndrome, effusions, liver or bone lesions, and effusions with a positive predictive value higher than 95%. Tumor markers are useful as an aid in the evaluation of the risk of cancer of these patients with suspected cancer and may be useful to reduce the hospitalization time, morbidity, and the number of diagnostic tests required for diagnosis.


Asunto(s)
Antígenos de Neoplasias/sangre , Biomarcadores de Tumor/sangre , Neoplasias/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígeno CA-19-9/biosíntesis , Antígeno Carcinoembrionario/biosíntesis , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias/metabolismo , Sensibilidad y Especificidad
8.
Gan To Kagaku Ryoho ; 39(4): 653-6, 2012 Apr.
Artículo en Japonés | MEDLINE | ID: mdl-22504696

RESUMEN

A 66-year-old male with a chief complaint of dysphagia was admitted to our hospital. Upper gastrointestinal endoscopy revealed a type 3 tumor on the gastric upper body, and pathological examinations of the biopsy specimens revealed a poorly differentiated adenocarcinoma. Computed tomography (CT) of the abdomen showed significant wall thickness of the stomach, and regional and para-aortic lymph node metastases. The CA19-9 level was high: 978 U/mL on admission. He received neoadjuvant chemotherapy using S-1 (120 mg/body, days 1-21) and cisplatin (108 mg/body, days 8) for faradvanced gastric cancer. After neoadjuvant chemotherapy, upper gastrointestinal endoscopy revealed that the gastric carcinoma had significant reductions in the size of its tumors, and CT showed that the lymph node metastases had disappeared, leading to a partial response. He underwent total gastrectomy, distal pancreatectomy, splenectomy and Roux-en Y reconstruction. Pathological examination of the resected specimens showed a small number of cancer cells in the submucosal layer, suggesting a Grade 2 pathological response, and gave a positive reaction to CA19-9 staining. The postoperative CA19-9 level decreased to a normal level. This case is diagnosed as CA19-9-producing gastric cancer. He was treated on an outpatient basis with adjuvant therapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno CA-19-9/biosíntesis , Terapia Neoadyuvante , Neoplasias Gástricas/tratamiento farmacológico , Anciano , Antígeno CA-19-9/sangre , Cisplatino/administración & dosificación , Combinación de Medicamentos , Humanos , Masculino , Ácido Oxónico/administración & dosificación , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/cirugía , Tegafur/administración & dosificación , Tomografía Computarizada por Rayos X
9.
Kyobu Geka ; 64(10): 951-3, 2011 Sep.
Artículo en Japonés | MEDLINE | ID: mdl-21899137

RESUMEN

A 58-year-old female was admitted to our hospital for investigation of serum elevation of carbohydrate antigen (CA 19-9). Computed tomography of the chest revealed a spiculated pulmonary nodule with the longest diameter of 3.7 cm in the right lower lobe. The diagnosis of lung adenocarcinoma was made. The patient underwent right lower lobectomy with lymphnode dissection. Histological examination revealed acinar type adenocarcinoma. The tumor was classified as stage IB with T2aN0M0. Immunohistochemically, the tumor cells stained positively for CA19-9. The serum CA19-9 level returned to a normal level after operation, but increased again with mediastinal lymphnode metastasis and brain metastasis. She died after an operation in 16 months.


Asunto(s)
Antígeno CA-19-9/biosíntesis , Carcinoma de Células Acinares/metabolismo , Neoplasias Pulmonares/metabolismo , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad
10.
Kyobu Geka ; 64(6): 483-6, 2011 Jun.
Artículo en Japonés | MEDLINE | ID: mdl-21682047

RESUMEN

A 76-year-old man, who had underwent radiation for laryngeal cancer 5 years before, was pointed out abnormal pulmonary lesion on computed tomography. The 4.6 cm-sized lesion was seen in the upper lobe of the left lung. Endoscopic brushing cytology revealed adenocarcinoma. The patient was diagnosed as primary lung cancer of T2N0M0, clinical stage IB. Preoperative serum CA19-9 was elevated to 250 U/ml, although other tumor markers were within normal limits. The patient underwent left upper lobectomy with mediastinal lymph node dissection. Histologically, the lesion was diagnosed as well differentiated adenocarcinoma, mucinous subtype of bronchioloalveolar carcinoma (BAC) in World Health Organization (WHO) classification. Immunohistochemistry shows positive for CA19-9 and thyroid transcription factor-1 (TTF-1).


Asunto(s)
Adenocarcinoma Bronquioloalveolar/metabolismo , Adenocarcinoma/metabolismo , Biomarcadores de Tumor/biosíntesis , Antígeno CA-19-9/biosíntesis , Neoplasias Pulmonares/metabolismo , Anciano , Humanos , Masculino
11.
Cells ; 10(5)2021 05 10.
Artículo en Inglés | MEDLINE | ID: mdl-34068719

RESUMEN

Circulation tumor cells (CTCs) play an important role in metastasis and highly correlate with cancer progression; thus, CTCs could be considered as a powerful diagnosis tool. Our previous studies showed that the number of CTCs could be utilized for recurrence prediction in colorectal cancer (CRC); however, the odds ratio was still lower than five. To improve prognosis in CRC patients, we analyzed CTC clusters/microemboli, CTC numbers, and carcinoembryonic antigen (CEA)/carbohydrate antigen 19-9 (CA19-9) levels using a self-assembled cell array (SACA) chip system for recurrence prediction. In CRC patients, the presence of CTC clusters/microemboli may have higher correlation in metastasis when compared to the high number of CTCs. Additionally, when both the number of CTCs and serum CEA levels are high, very high odds ratios of 24.4 and 17.1 are observed in patients at all stages and stage III of CRC, respectively. The high number of CTCs and CTC clusters/microemboli simultaneously suggests the high chance of relapse (odds ratio 8.4). Overall, the characteristic of CTC clusters/microemboli, CEA level, and CTC number have a clinical potential to enhance CRC prognosis.


Asunto(s)
Antígeno CA-19-9/biosíntesis , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Células Neoplásicas Circulantes/metabolismo , Pronóstico , Anciano , Algoritmos , Biomarcadores de Tumor/sangre , Antígeno Carcinoembrionario/biosíntesis , Neoplasias Colorrectales/diagnóstico , Embolia , Femenino , Humanos , Inmunoensayo , Estimación de Kaplan-Meier , Biopsia Líquida , Metástasis Linfática , Masculino , Microscopía Fluorescente , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Oportunidad Relativa , Reconocimiento de Normas Patrones Automatizadas , Fenotipo , Curva ROC , Reproducibilidad de los Resultados
12.
BMC Cancer ; 10: 570, 2010 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-20961434

RESUMEN

BACKGROUND: Gallbladder cancer typically follows an aggressive course, with chemotherapy the standard of care for advanced disease; complete remissions are rarely encountered. The epidermal growth factor receptor (EGFR) is a promising therapeutic target but the activity of single agent oral EGFR tyrosine kinase inhibitors is low. There have been no previous reports of chemotherapy plus an EGFR-tyrosine kinase inhibitor (TKI) to treat gallbladder cancer or correlations of response with the mutation status of the tyrosine kinase domain of the EGFR gene. CASE PRESENTATION: A 67 year old man with metastatic gallbladder cancer involving the liver and abdominal lymph nodes was treated with gemcitabine (1000 mg/m2) on day 1 and 8 every 21 days as well as daily erlotinib (100 mg). After four cycles of therapy, the CA 19-9 normalized and a PET/CT showed a complete remission; this response was maintained by the end of 12 cycles of therapy. Gemcitabine was then discontinued and single agent erlotinib was continued as maintenance therapy. The disease remains in good control 18 months after initiation of therapy, including 6 months on maintenance erlotinib. The only grade 3 toxicity was a typical EGFR-related skin rash. Because of the remarkable response to erlotinib plus gemcitabine, we performed tumor genotyping of the EGFR gene for response predicting mutations in exons 18, 19 and 21. This disclosed the wild-type genotype with no mutations found. CONCLUSION: This case report demonstrates a patient with stage IV gallbladder cancer who experienced a rarely encountered complete, prolonged response after treatment with an oral EGFR-TKI plus chemotherapy. This response occurred in the absence of an EGFR gene mutation. These observations should inform the design of clinical trials using EGFR-TKIs to treat gallbladder and other biliary tract cancers; such trials should not select patients based on EGFR mutation status.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Desoxicitidina/análogos & derivados , Receptores ErbB/genética , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Neoplasias de la Vesícula Biliar/genética , Mutación , Quinazolinas/administración & dosificación , Anciano , Antígeno CA-19-9/biosíntesis , Análisis Mutacional de ADN , Desoxicitidina/administración & dosificación , Clorhidrato de Erlotinib , Exones , Humanos , Metástasis Linfática , Masculino , Tomografía de Emisión de Positrones/métodos , Resultado del Tratamiento , Gemcitabina
13.
Urol Int ; 84(1): 116-8, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20173382

RESUMEN

Primary adenocarcinoma of the urinary tract producing tumor markers is extremely rare. We report 2 cases of advanced adenocarcinoma of the urinary tract producing carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 125 (CA125), which were completely resected after induction chemotherapy with paclitaxel and carboplatin. Patient 1 was a 72-year-old woman with adenocarcinoma of the right renal pelvis and ureter. Patient 2 was a 73-year-old woman with adenocarcinoma of the bladder. Serum levels of CEA, CA19-9 and CA125 were extremely elevated in both cases. They were successfully treated with paclitaxel puls carboplatin followed by surgery. Both patients were proved to have achieved pathological complete regression by surgical specimens and have been alive without recurrence for more than 18 and 6 months, respectively.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno Ca-125/biosíntesis , Antígeno CA-19-9/biosíntesis , Carboplatino/administración & dosificación , Antígeno Carcinoembrionario/biosíntesis , Paclitaxel/administración & dosificación , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento
14.
Mol Ther ; 16(5): 979-84, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18388964

RESUMEN

Rexin-G is a pathotropic retroviral vector displaying a von Willebrand factor-targeting motif and expressing a dominant negative cyclin G1 gene. We undertook a phase I trial of intravenous (i.v.) administration of Rexin-G in patients with gemcitabine refractory, metastatic pancreatic adenocarcinoma. Twelve patients were treated. Dose escalation was performed from a dose of 1 x 10(11) colony forming units (CFU) per cycle to 6 x 10(11) CFU per cycle. The treatment was well tolerated. One dose-limiting toxicity (DLT) at dose level 2 (1.5 x 10(11) CFU per cycle) was observed, consisting of grade 3 transaminitis. There was no detection of replication-competent virus in patients' peripheral blood mononuclear cells (PBMCs) or viral integration in DNA obtained from PBMCs, and no development of neutralizing antibodies. No evidence of antitumor activity was observed. The best objective response was progressive disease in 11 of the 12 study patients, while 1 patient showed radiographically stable disease with clinical deterioration and increase in the CA19.9 tumor marker. Median time to progression was 32 days. The median duration of survival of the study patients was 3.5 months from treatment initiation. Rexin-G is well tolerated in doses up to 6 x 10(11) CFU in patients with recurrent pancreatic cancer, but there was no evidence of clinical antitumor activity.


Asunto(s)
Ciclinas/metabolismo , Terapia Genética/métodos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Retroviridae/genética , Adulto , Anciano , Antígeno CA-19-9/biosíntesis , Ciclina G , Ciclina G1 , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Femenino , Vectores Genéticos , Humanos , Infusiones Intravenosas , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Células Madre , Resultado del Tratamiento , Gemcitabina
15.
Eur J Cancer ; 111: 94-106, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30826661

RESUMEN

BACKGROUND: The benefit of second-line chemotherapy (L2) over standard first-line (L1) gemcitabine plus cisplatin (GEMCIS) or oxaliplatin (GEMOX) chemotherapy in advanced biliary tract cancer (aBTC) is unclear. Our aim was to identify and validate prognostic factors for overall survival (OS) with L2 in aBTC to guide clinical decisions in this setting. METHODS: We performed a retrospective analysis of four prospective patient cohorts: a development cohort (28 French centres) and three validation cohorts from Italy, UK and France. All consecutive patients with aBTC receiving L2 after GEMCIS/GEMOX L1 between 2003 and 2016 were included. The association of clinicobiological data with OS was investigated in univariate and multivariate Cox analyses. A simple score was derived from the multivariate model. RESULTS: The development cohort included 405 patients treated with L1 GEMOX (91%) or GEMCIS. Of them, 55.3% were men, and median age was 64.8 years. Prior surgical resection was observed in 26.7%, and 94.8% had metastatic disease. Performance status (PS) was 0, 1 and 2 in 17.8%, 52.4% and 29.7%, respectively. Among 22 clinical parameters, eight were associated with OS in univariate analysis. In multivariate analysis, four were independent prognostic factors (p < 0.05): PS, reason for L1 discontinuation, prior resection of primary tumour and peritoneal carcinomatosis. The model had the Harrell's concordance index of 0.655, a good calibration and was validated in the three external cohorts (N = 392). CONCLUSION: We validated previously reported predictive factors of OS with L2 and identified peritoneal carcinomatosis as a new pejorative factor in nearly 800 patients. Our model and score may be useful in daily practice and for future clinical trial design.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Biliar/mortalidad , Neoplasias del Sistema Biliar/patología , Neoplasias del Sistema Biliar/terapia , Nomogramas , Anciano , Antígeno CA-19-9/biosíntesis , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Peritoneales/patología , Pronóstico , Estudios Retrospectivos , Terapia Recuperativa/métodos , Resultado del Tratamiento
16.
J Cell Biochem ; 104(3): 745-55, 2008 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-18275060

RESUMEN

BACKGROUND: Cholangiocarcinoma (CC) is devastating neoplasm and very few specific biomarkers could be used in clinical diagnosis. A study was taken to find novel serum biomarkers for CC. METHODS: Surface enhanced laser desorption/ionization (SELDI) technology was used to analyze 427 serum samples including 56 CCs, 49 hepatobiliary diseases, 269 other cancer control, and 53 healthy individuals. The candidates were isolated and identified by SDS-PAGE, ESI/MS-MS, Western blot, and immunoprecipitation. Liver functions of CC patients were examined and enzyme-linked immunosorbent assay (ELISA) of transthyretin (TTR) and CA19-9 were further performed in some sets of serum samples. RESULTS: 13.76, 13.88, and 14.04 k m/z peaks in sera were significantly decreased in CC compared with the control groups (P < 0.001). Subsequently, these three peaks were identified as native TTR and its two variants. ELISA assay indicated that TTR levels were consistent with SELDI analysis in CC compared with healthy control and benign diseases of hepatobiliary (P < 0.001). Liver function test levels were obviously elevated for CC patients. TTR combining with CA19-9 to differentiate CC from benign hepatobiliary diseases showed sensitivity and specificity were 98.2% and 100%, respectively. CONCLUSION: The levels of TTR were significantly down-regulated in sera of CC patients and may be complementary markers of CA19-9 in diagnosis for CC.


Asunto(s)
Neoplasias de los Conductos Biliares/sangre , Neoplasias de los Conductos Biliares/metabolismo , Conductos Biliares Intrahepáticos/metabolismo , Colangiocarcinoma/sangre , Colangiocarcinoma/metabolismo , Regulación Neoplásica de la Expresión Génica , Prealbúmina/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Antígeno CA-19-9/biosíntesis , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad
17.
Kyobu Geka ; 61(10): 873-6, 2008 Sep.
Artículo en Japonés | MEDLINE | ID: mdl-18788378

RESUMEN

We report 2 cases of resected CA19-9 producing adenocarcinoma of the lung. Immunohistochemical studies of the specimens in 2 cases showed positive staining for CA19-9 in most of tumor cells. The serum CA19-9 levels decreased after operations and effective chemotherapy in these cases. But the serum CA19-9 levels increased with regrowth of tumors or with no therapeutic gain by chemotherapy. The serum CA19-9 level was useful to evaluate the therapeutic effect of surgery and chemotherapy, and may be effective in detecting the recurrence of lung cancer.


Asunto(s)
Adenocarcinoma/metabolismo , Adenocarcinoma/cirugía , Biomarcadores de Tumor/biosíntesis , Antígeno CA-19-9/biosíntesis , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirugía , Neumonectomía , Adenocarcinoma/diagnóstico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/sangre , Antígeno CA-19-9/sangre , Carboplatino/administración & dosificación , Terapia Combinada , Docetaxel , Resultado Fatal , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Taxoides/administración & dosificación , Resultado del Tratamiento
18.
Medicine (Baltimore) ; 97(52): e13858, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30593188

RESUMEN

RATIONALE: Primary pancreatic tuberculosis is extremely rare, it presents with non-specific clinical symptoms and imaging features; it may be falsely identified as a malignancy of the pancreas. PATIENT CONCERNS: A 41-year-old male with no history of tuberculosis presented to our hospital with a 2-week history of jaundice. DIAGNOSES: Abdominal computed tomography (CT) showed a heterogeneous irregular hypodense mass in the head of the pancreas causing dilatation of the common bile duct (CBD), and it was enhanced after infusion of contrast material. Serum cancer antigen (CA) 19-9 was 124 U/mL (normal: 0-40 U/mL). He was preoperatively diagnosed as having a pancreatic carcinoma. INTERVENTIONS: A Whipple procedure (pancreaticoduodenectomy) was performed. The pancreatic tuberculosis was confirmed based on the postoperative histopathologic specimens and acid-fast stain of the drainage. Then isoniazid, rifampicin, and ethambutol were given for 6 months. OUTCOMES: The patient recovered very well. There was no evidence of tuberculosis recurrence, and the patient remained free of symptoms during the follow-up examination 1 year after surgery. LESSONS: Pancreatic tuberculosis should be considered when the mass is located on the head of the pancreas even with elevated serum CA19-9 levels.


Asunto(s)
Enfermedades Pancreáticas/diagnóstico , Tuberculosis Gastrointestinal/diagnóstico , Adulto , Antituberculosos/uso terapéutico , Antígeno CA-19-9/biosíntesis , Diagnóstico Diferencial , Humanos , Masculino , Enfermedades Pancreáticas/tratamiento farmacológico , Enfermedades Pancreáticas/cirugía , Neoplasias Pancreáticas/diagnóstico , Pancreaticoduodenectomía/métodos , Tuberculosis Gastrointestinal/tratamiento farmacológico , Tuberculosis Gastrointestinal/cirugía
19.
Anticancer Res ; 27(4A): 1981-8, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17649809

RESUMEN

BACKGROUND: Sialyl Lewis x (SLeX), sialyl Lewis a (SLeA), Lewis Y (LeY) and the Thomsen-Friedenreich (TF) antigen are carbohydrate motifs that mediate the adhesion between tumour cells and the endothelium. These antigens are usually not expressed in non-malignant tissue. Overexpression of SLeX and SLeA is combined with poor prognosis and malignant relapse. In this study, we analysed the combined expression of SLeX, SLeA, LeY and TF in normal squamous epithelium tissue of the penis shaft, glans and foreskin and in addition of the vagina and vulva. MATERIALS AND METHODS: Paraffin-embedded slides of vaginal tissue (8), vulva tissue (8) and penis shaft (8) and glans tissue (8) were fixed and incubated with monoclonal antibodies against SLeX (IgM), SLeA (IgM), LeY (IgM) and TF (IgM). Staining reaction was performed with ABC reagent. The intensity of immunohistochemical reaction on images of the slides was analyzed using a semiquantitative score. RESULTS: Strong focal expression of both sialyl Lewis antigens was found in the uretra of the penis shaft and on epithelial tissue of the glans, and permanent moderate expression of SLeX and SLeA in squamous epithelial tissue of the vagina. Moderate expression of TF was observed in male squamous epithelial tissues of the glans and foreskin and faint expression of TF was found in vulval epithelial tissue. Faint expression of Le Y was observed in female vulval epithelial tissue. CONCLUSION: Expression of SLeX, SLeA, LeY and especially of the TF antigen in normal non malignant epithelial tissue is surprising and can be explained by the function of this tissue in human reproduction. In addition, moderate TF expression seems to be restricted to epithelial tissue of the penis glans and foreskin.


Asunto(s)
Antígenos de Neoplasias/biosíntesis , Biomarcadores de Tumor/biosíntesis , Epitelio/metabolismo , Pene/metabolismo , Vagina/metabolismo , Antígenos de Carbohidratos Asociados a Tumores/biosíntesis , Antígeno CA-19-9/biosíntesis , Femenino , Humanos , Inmunohistoquímica , Antígenos del Grupo Sanguíneo de Lewis/biosíntesis , Masculino , Oligosacáridos/biosíntesis , Antígeno Sialil Lewis X
20.
World J Gastroenterol ; 13(29): 3962-6, 2007 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-17663510

RESUMEN

AIM: To assess the diagnostic accuracy of endoscopic ultrasound (EUS), fluid tumor markers and cytology in distinguishing benign from (pre)malignant pancreatic cystic lesions. METHODS: 46 consecutive patients, referred to a gastroenterologist and surgeon for a symptomatic or incidental pancreatic cyst, were reviewed. EUS, cytology, and carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) levels were compared with the final diagnosis, based on surgical pathology and/or imaging follow-up of at least 12 mo. Cysts were classified as benign (pseudocyst, serous cystadenoma) or malignant/pre-malignant (mucinous cystic neoplasm). Receiver-operator characteristics (ROC) curve analysis was performed. RESULTS: The mean age was 56 years; 29% were male and median cyst diameter was 3 cm. Final outcome was obtained in 41 (89%) patients. Twenty-three (56%) of these 41 had surgical pathology. Twenty-three (56%) had benign lesions and 18 (44%) had malignant/pre-malignant lesions. Sensitivity, specificity and positive and negative predictive value of EUS alone to distinguish benign from malignant/premalignant pancreatic cystic lesions were 50%, 56%, 36% and 54% and for cytology were 71%, 96%, 92% and 85%, respectively. The corresponding values for the ROC-derived ideal cutoffs were 75%, 90%, 75%, 90% for CA 19-9 (> 37 U/mL) and 70%, 85%, 79% and 78% for CEA (> 3.1 ng/mL). Subgroup analysis of those with surgical pathology yielded almost identical performance and cutoffs. CONCLUSION: Cytology and cyst fluid tumor marker analysis is a very useful tool in distinguishing benign from (pre)malignant pancreatic cystic lesions.


Asunto(s)
Antígeno CA-19-9/biosíntesis , Antígeno Carcinoembrionario/biosíntesis , Endoscopía/métodos , Ultrasonografía/métodos , Anciano , Biomarcadores de Tumor , Biopsia con Aguja Fina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Páncreas/patología , Curva ROC , Sensibilidad y Especificidad , Resultado del Tratamiento
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