Résumé
Chimeric antigen receptor T cell (CAR-T) therapy has shown remarkable success in treating hematological malignancies. However, CAR-T therapy for solid tumors is still limited due to the unique solid-tumor microenvironment and heterogeneous target antigen expression, which leads to an urgent need of combining other therapies. At present, nano delivery system has become one of the most promising directions for the development of anti-tumor drugs. Based on the background of CAR-T and tumor treatment, we focus on the research progress of nanomedicine combined with CAR-T therapy, and systematically review the strategies and examples in recent years in the aspects of in vivo delivery of mRNA, regulation of tumor microenvironment, combination with photothermal therapy. And we also look forward to the future direction of this filed. .
Sujets)
Humains , Récepteurs chimériques pour l'antigène/usage thérapeutique , Préparations pharmaceutiques/métabolisme , Antigènes néoplasiques/métabolisme , Tumeurs du poumon/métabolisme , Tumeurs/métabolisme , Lymphocytes T , Microenvironnement tumoral , Nanoparticules/usage thérapeutiqueRésumé
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding, and which has a greater affinity. Fusion of specific antigens to extracellular domain of CTLA4 represents a promising approach to increase the immunogenicity of DNA vaccines. In this study, we evaluated this interesting approach for CTLA4 enhancement on prostate stem cell antigen (PSCA)-specific immune responses and its anti-tumor effects in a prostate cancer mouse model. Consequently, we constructed a DNA vaccine containing the PSCA and the CTLA-4 gene. Vaccination with the CTLA4-fused DNA not only induced a much higher level of anti-PSCA antibody, but also increased PSCA-specific T cell response in mice. To evaluate the anti-tumor efficacy of the plasmids, murine models with PSCA-expressing tumors were generated. After injection of the tumor-bearing mouse model, the plasmid carrying the CTLA4 and PSCA fusion gene showed stronger inhibition of tumor growth than the plasmid expressing PSCA alone. These observations emphasize the potential of the CTLA4-fused DNA vaccine, which could represent a promising approach for tumor immunotherapy.
Sujets)
Animaux , Mâle , Souris , Antigènes néoplasiques/usage thérapeutique , Vaccins anticancéreux/usage thérapeutique , Antigène CTLA-4/usage thérapeutique , Protéines tumorales/usage thérapeutique , Plasmides/usage thérapeutique , Tumeurs de la prostate/thérapie , Vaccins à ADN/usage thérapeutique , Antigènes néoplasiques/immunologie , Antigènes néoplasiques/métabolisme , Vaccins anticancéreux/immunologie , Antigène CTLA-4/génétique , Antigène CTLA-4/immunologie , Modèles animaux de maladie humaine , Protéines liées au GPI/immunologie , Protéines liées au GPI/métabolisme , Protéines liées au GPI/usage thérapeutique , Protéines tumorales/immunologie , Protéines tumorales/métabolisme , Plasmides/génétique , Tumeurs de la prostate/immunologie , Protéines de fusion recombinantes/usage thérapeutique , Vaccins à ADN/génétiqueRésumé
BACKGROUND: To evaluate the macrophage migration inhibitory factor and E-selectin levels in patients with acute coronary syndrome. MATERIALS/METHODS: We examined the plasma migration inhibitory factor and E-selectin levels in 87 patients who presented with chest pain at our hospital. The patients were classified into two groups according to their cardiac status. Sixty-five patients had acute myocardial infarction, and 22 patients had non-cardiac chest pain (non-coronary disease). We designated the latter group of patients as the control group. The patients who presented with acute myocardial infarction were further divided into two subgroups: ST-elevated myocardial infarction (n = 30) and non-ST elevated myocardial infarction (n = 35). RESULTS: We found higher plasma migration inhibitory factor levels in both acute myocardial infarction subgroups than in the control group. However, the E-selectin levels were similar between the acute myocardial infarction and control patients. In addition, we did not find a significant difference in the plasma migration inhibitory factor levels between the ST elevated myocardial infarction and NST-elevated myocardial infarction subgroups. DISCUSSION: The circulating concentrations of migration inhibitory factor were significantly increased in acute myocardial infarction patients, whereas the soluble E-selectin levels were similar between acute myocardial infarction patients and control subjects. Our results suggest that migration inhibitory factor may play a role in the atherosclerotic process. .
Sujets)
Animaux , Femelle , Souris , /métabolisme , Interféron gamma/métabolisme , Tumeurs mammaires de l'animal/immunologie , Sphéroïdes de cellules/immunologie , Lymphocytes T cytotoxiques/métabolisme , Lymphocytes T auxiliaires/métabolisme , Alginates , Antigènes néoplasiques/immunologie , Antigènes néoplasiques/métabolisme , Lignée cellulaire tumorale , Mouvement cellulaire , Chitosane , /génétique , /immunologie , Acide glucuronique , Granzymes/métabolisme , Acides hexuroniques , Immunité cellulaire , Interféron gamma/génétique , Interféron gamma/immunologie , Tumeurs mammaires de l'animal/génétique , Tumeurs mammaires de l'animal/métabolisme , Tumeurs mammaires de l'animal/anatomopathologie , Sphéroïdes de cellules/métabolisme , Sphéroïdes de cellules/anatomopathologie , Lymphocytes T cytotoxiques/immunologie , Lymphocytes T auxiliaires/immunologie , Microenvironnement tumoralRésumé
OBJECTIVE: All patients with stage IB1 cervical cancer do not need to undergo parametrectomy. Some low-risk criteria for parametrial involvement (PI) have been proposed based on pathological findings. The aim of this study was to determine pretreatment risk factors for PI in stage IB1 cervical cancer. METHODS: We retrospectively reviewed 115 patients with stage IB1 cervical cancer who underwent radical hysterectomy or radical trachelectomy. Magnetic resonance imaging (MRI) was performed and serum concentrations of squamous cell carcinoma antigen (SCC-Ag) and cancer antigen 125 (CA-125) were determined in all patients before initial treatment. The following pretreatment factors were investigated: histological variant, maximum tumor diameter, tumor volume (volume index), pelvic lymph node enlargement, and serum tumor markers. Logistic regression analysis was used to select the independent risk factors for PI. RESULTS: Eighteen of the 115 patients (15.7%) were pathologically diagnosed with PI. Multivariate analysis confirmed the following independent risk factors for PI: MRI-based tumor diameter > or =25 mm (odds ratio [OR], 9.9; 95% confidence interval [CI], 2.1 to 48.1), MRI-based volume index > or =5,000 mm3 (OR, 13.3; 95% CI, 1.4 to 125.0), and positive serum tumor markers SCC-Ag > or =1.5 ng/mL or CA-125 > or =35 U/mL (OR, 5.7; 95% CI, 1.3 to 25.1). Of 53 patients with no risk factors for PI, none had PI. CONCLUSION: Less radical surgery may become one of the treatment options for stage IB1 cervical cancer patients with MRI-based tumor diameter <25 mm, MRI-based volume index <5,000 mm3, and negativity for SCC-Ag and CA-125.
Sujets)
Adulte , Sujet âgé , Femelle , Humains , Adulte d'âge moyen , Jeune adulte , Antigènes néoplasiques/métabolisme , Marqueurs biologiques tumoraux/métabolisme , Hystérectomie/méthodes , Métastase lymphatique , Imagerie par résonance magnétique/méthodes , Stadification tumorale , Biais de l'observateur , Études rétrospectives , Facteurs de risque , Serpines/métabolisme , Tumeurs du col de l'utérus/métabolismeRésumé
OBJECTIVE: Epithelial cell adhesion molecule (EpCAM) has experienced a renaissance lately as a binding site for targeted therapy as well as a prognostic marker in epithelial malignancies. Aim of this study was to study EpCAM as a potential prognostic marker in epithelial ovarian cancer (EOC). METHODS: EpCAM expression was assessed by immunohistochemistry on paraffin-embedded primary EOC-tissue samples. EpCAM overexpression was defined as an expression of EpCAM of 76% to 100%. Tissue samples and clinical data were systematically collected within the international and multicenter "Tumorbank Ovarian Cancer" network. RESULTS: Seventy-four patients, diagnosed with EOC between 1994 and 2009, were included in the study (median age, 56 years; range, 31 to 86 years). The majority of the patients (81.1%) presented with an advanced stage International Federation of Gynecology and Obstetrics (FIGO) III/IV disease. Histology was of the serous type in 41 patients (55.4%), endometrioid in 19 (25.6%), and mucinous in 14 (19%). EpCAM was overexpressed in 87.7%. Serous tumors overexpressed EpCAM significantly more often than mucinous tumors (87.8% vs. 78.6%, p=0.045); while no significant difference was noted between the other histological subgroups. EpCAM overexpression was significantly associated with a better progression free survival and higher response rates to platinum based chemotherapy (p=0.040 and p=0.048, respectively). EpCAM was identified as an independent prognostic marker for overall survival (p=0.022). CONCLUSION: Our data indicate a significant association of EpCAM overexpression with a more favorable survival in EOC-patients. Serous cancers showed a significant EpCAM overexpression compared to mucinous types. Larger multicenter analyses are warranted to confirm these findings.
Sujets)
Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Femelle , Humains , Adulte d'âge moyen , Antigènes néoplasiques/métabolisme , Antinéoplasiques/usage thérapeutique , Carboplatine/usage thérapeutique , Molécules d'adhérence cellulaire/métabolisme , Estimation de Kaplan-Meier , Protéines tumorales/métabolisme , Stadification tumorale , Tumeurs épithéliales épidermoïdes et glandulaires/diagnostic , Composés organiques du platine/usage thérapeutique , Tumeurs de l'ovaire/diagnostic , Paclitaxel/usage thérapeutique , Pronostic , Banques de tissus , Résultat thérapeutique , Marqueurs biologiques tumoraux/métabolismeRésumé
No abstract available.
Sujets)
Femelle , Humains , Antigènes néoplasiques/métabolisme , Antinéoplasiques/usage thérapeutique , Molécules d'adhérence cellulaire/métabolisme , Tumeurs épithéliales épidermoïdes et glandulaires/diagnostic , Composés organiques du platine/usage thérapeutique , Tumeurs de l'ovaire/diagnostic , Marqueurs biologiques tumoraux/métabolismeRésumé
No abstract available.
Sujets)
Adulte , Humains , Antibiotiques antinéoplasiques/administration et posologie , Antigènes CD34/métabolisme , Antigènes CD56/métabolisme , Antigènes néoplasiques/métabolisme , Carcinome hépatocellulaire/métabolisme , Molécules d'adhérence cellulaire/métabolisme , Chimioembolisation thérapeutique , Doxorubicine/administration et posologie , Huile éthiodée/composition chimique , Hépatite B/diagnostic , Cirrhose du foie/diagnostic , Tumeurs du foie/anatomopathologie , Imagerie par résonance magnétique , TomodensitométrieRésumé
Combined hepatocellular carcinoma and cholangiocarcinoma (combined HCC-CC) is a rare subtype of primary liver cancer. We investigated the histopathologic features of transitional or intermediate areas in 21 combined HCC-CCs and immunophenotypes using different hepatic progenitor cell markers (CK7, CK19, c-kit, NCAM, and EpCAM). Major histologic findings of transitional or intermediate areas of 21 combined HCC-CCs included strands/trabeculae of small, uniform, oval-shaped cells with scant cytoplasm and hyperchromatic nuclei embedded within an abundant stroma, small cells with an antler-like anastomosing pattern, and solid nests of intermediate hepatocyte-like cells surrounded by small cells in periphery, in order of frequency. The intermediate area of one tumor was composed predominantly of spindle cells arranged in short fascicles. Immunophenotype of tumor cells with intermediate morphology suggested a progenitor cell origin for this tumor. Clinical findings of combined HCC-CC showed a closer resemblance with those of HCC than those of CC. In univariate analysis, tumor size, TNM stage, and serum alpha-fetoprotein levels showed a significant association with poor patient survival. Serum alpha-fetoprotein level was an independent prognostic indicator in multivariate analysis. In conclusion, an awareness of the clinicopathologic features, specifically the various morphologic features of intermediate areas in this tumor, is essential for prevention of potential misdiagnosis as another tumor.
Sujets)
Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Antigènes néoplasiques/métabolisme , Carcinome hépatocellulaire/anatomopathologie , Molécules d'adhérence cellulaire/métabolisme , Cholangiocarcinome/anatomopathologie , Immunophénotypage , Kératine-19/métabolisme , Kératine-7/métabolisme , Tumeurs du foie/anatomopathologie , Molécules d'adhérence cellulaire neurales/métabolisme , Pronostic , Protéines proto-oncogènes c-kit/métabolisme , Alphafoetoprotéines/analyseRésumé
No abstract available.
Sujets)
Humains , Mâle , Adulte d'âge moyen , Antigènes néoplasiques/métabolisme , Tumeurs osseuses/diagnostic , Évolution de la maladie , Interférons/usage thérapeutique , Tumeurs du foie/diagnostic , Mélanome/diagnostic , Protéines tumorales/métabolisme , Tomographie par émission de positons , Tumeurs du rectum/diagnostic , Protéines S100/métabolisme , Tamoxifène/usage thérapeutique , TomodensitométrieRésumé
Schwannoma, also referred to as neurilemmoma, is a benign tumor of peripheral nerve arising from Schwann cells that form the neural sheath. Schwannoma of ophthalmic interest is rare although it has been reported in relation with the orbit, and less frequently with the uveal tract and conjunctiva. Isolated eyelid schwannoma is extremely uncommon. Up until now, only eight cases have been reported in literature. Herein, we report two cases of eyelid schwannoma.
Sujets)
Antigènes néoplasiques/métabolisme , Tumeurs de la paupière/métabolisme , Tumeurs de la paupière/anatomopathologie , Tumeurs de la paupière/chirurgie , Femelle , Humains , Immunochimie , Mâle , Antigènes spécifiques du mélanome , Adulte d'âge moyen , Protéines tumorales/métabolisme , Neurinome/métabolisme , Neurinome/anatomopathologie , Neurinome/chirurgie , Maladies rares , Protéines S100/métabolisme , Jeune adulteRésumé
We present a case of perivascular epithelioid cell tumors (PEComas) in the abdominal cavity at the falciform ligament. A 30-yr-old Korean man visited to hospital for the evaluation of a growing, palpable abdominal mass. He had felt the mass growing over 6 months. There was no family or personal history of tuberous sclerosis. The resected specimen showed a mass of 8.0x7.0x5.5 cm in size. Histological examination showed sheets of spindle-to-epithelioid cells with clear-to-eosinophilic cytoplasm. Immunohistochemically, tumor cells were positive for HMB-4 (gp100) and smooth muscle actin. They were also positive for the S-100, which is a marker of neurogenic and melanocytic tumors. Patient was treated with radical resection of tumor without any adjuvant therapy. He is well and on follow-up visits without tumor recurrence.
Sujets)
Adulte , Humains , Mâle , Tumeurs de l'abdomen/diagnostic , Actines/métabolisme , Antigènes néoplasiques/métabolisme , Ligaments/anatomopathologie , Protéines tumorales/métabolisme , Tumeurs des cellules épithélioïdes périvasculaires/diagnostic , Protéines S100/métabolisme , TomodensitométrieRésumé
Renal oncocytoma, conventional RCC (granular cell type) and chromophobe RCC have different prognosis. Sometimes differentiation between them is difficult in HandE slides. In a 5-year study of 128 renal tumors, we selected 76 cases [30 conventional RCC (CRCC), 16 papillary RCC, 21 chromophobe RCC (ChRCC), 8 oncocytoma, 1 collecting duct carcinoma (cdc)] and staining with Hale's colloidal iron, CK7, CK8, CK18, CK19, CK20, Vimentin, EMA, CD10 and RCC marker were done. No significant difference was seen between renal tumor subtypes with CK8, CK18, CK19, CK20 and EMA. The most useful markers were Vimentin, CK7, CD10, RCC marker and Hale's colloidal iron. Hale's colloidal iron staining with diffuse reticular fine cytoplasmic pattern was present in ChRCCs, but was absent in other subtypes and oncocytomas. Vimentin, CK7, CD10, RCC marker and Hale's colloidal iron can be used for the differential diagnosis of problematic epithelial tumors of kidney (CRCC, ChRCC and oncocytoma) - i.e. ChRCC: Vimentin, CD10 and RCC marker - negative, CK7 - positive and positive diffuse fine reticular cytoplasmic pattern of Hale's colloidal iron; oncocytoma: Vimentin, CK7, RCC marker and CD10 - negative and Hale's colloidal iron - negative; CRCC: CK7 - negative, Vimentin, CD10 and RCC marker - positive and Hale's colloidal iron - negative.
Sujets)
Adénome oxyphile/diagnostic , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Antigènes néoplasiques/métabolisme , Néphrocarcinome/diagnostic , Diagnostic différentiel , Femelle , Humains , Kératine-7/métabolisme , Tumeurs du rein/diagnostic , Mâle , Adulte d'âge moyen , Mitogen-Activated Protein Kinases/métabolisme , Néprilysine/métabolisme , Marqueurs biologiques tumoraux/métabolisme , Vimentine/métabolismeSujets)
Humains , Marqueurs biologiques tumoraux/métabolisme , Mélanome/diagnostic , Mélanome/métabolisme , Tumeurs cutanées/diagnostic , Tumeurs cutanées/métabolisme , /métabolisme , Antigènes néoplasiques/métabolisme , Facteur de transcription associé à la microphtalmie/métabolisme , Immunohistochimie , Monophenol monooxygenase/métabolisme , /métabolismeRésumé
Clear cell tumor of the lung is a rare and very unusual benign pulmonary tumor. As clear cell tumor of the lung contains abundant cytoplasmic glycogen, this tumor is called "sugar tumor". We report a case of sugar tumor in a 64-yr-old man presenting as a round pulmonary nodule. On dynamic computed tomography (CT) scans, the solitary pulmonary nodule showed early wash-in enhancement with an early washout pattern like a lung malignancy. The patient underwent wedge resection for the tumor. Pathologic examination, including immunohistochemical studies, revealed that the nodule was a benign clear cell tumor, so-called "sugar tumor". Because only a small number of cases have been reported previously, clinical aspects, radiological characteristics on dynamic contrast-enhanced CT, and differential diagnosis of the tumor are not well established. Herein we present a clear cell tumor of the lung and discuss the clinical, radiological, and pathological features of the tumor.
Sujets)
Humains , Mâle , Adulte d'âge moyen , Antigènes néoplasiques/métabolisme , Diagnostic différentiel , Poumon/imagerie diagnostique , Tumeurs du poumon/diagnostic , Protéines tumorales/métabolisme , Tumeurs des cellules épithélioïdes périvasculaires/diagnostic , Nodule pulmonaire solitaire/diagnostic , TomodensitométrieRésumé
BACKGROUND: The molecular events that accompany the progression to adenocarcinoma (ADC) of the esophagus are poorly understood. Aberrant mucin receptor expression can contribute to increased cell growth and metastatic ability. AIM: The aim of this study was to establish a pattern for mucin (MUC) gene expression in the esophageal mucosa under normal and pathological conditions. SETTING: University Hospital Cancer Center Laboratory. Archived tissue samples studied in a retrospective fashion. MATERIALS AND METHODS: Tissue samples were obtained from the archives of patients with histological evidence of Barrett's esophagus (BE) progressing to ADC. Immunohistochemical analysis was performed using mouse monoclonal antibodies for MUC1, MUC2, MUC5AC, MUC6. Semiquantitative scoring of histological staining was performed using a linear scoring system: 0-staining absent; 1-staining in 0-25%; 2-staining in 25-50%; and 3-staining in 50-75% of the epithelium. The Binomial test was used to explore trends and differences in frequency of mucin expression along the pathological sequence. RESULTS: Only mild superficial staining of MUC1 was seen in normal squamous epithelium. MUC1 and MUC2 were uniformly expressed in all samples (7/7) of BE and dysplasia (P=0.008). MUC1 expression was upregulated (7/7) in progression to adenocarcinoma (P=0.008). The secretory mucins, MUC5AC and MUC6 showed a decrease in expression with progression from BE to dysplasia to ADC (P< 0.05). CONCLUSIONS: Downregulation of MUC5AC and MUC6 decreases mucosal protection against gastric acid. Increasing MUC1 expression is associated with progression from dysplasia to ADC. Upregulation of MUC2 reflects intestinal metaplasia in BE.
Sujets)
Adénocarcinome/métabolisme , Antigènes néoplasiques/métabolisme , Oesophage de Barrett/métabolisme , Tumeurs de l'oesophage/métabolisme , Oesophage/métabolisme , Régulation de l'expression des gènes tumoraux , Humains , Tumeurs de l'intestin/métabolisme , Métaplasie/métabolisme , Mucine-5AC , Mucine-1 , Mucine-2 , Mucine-6 , Mucines/métabolisme , États précancéreux/métabolisme , Études rétrospectives , Marqueurs biologiques tumoraux/métabolismeRésumé
In a review of 79 cases of gall bladder malignancy, nineteen cases were labelled as unusual tumors while sixty were diagnosed as adenocarcinoma. Alcian blue, PAS, Grimelius' and Masson trichrome stains were done. Expression of EMA, CEA and desmin was assessed (PAP). Histological subtype was revised, in eleven cases out of 19. Five tumors initially diagnosed as squamous cell carcinoma were found to be positive for mucin and CEA and hence were reclassified as adenosquamous carcinoma. Three undifferentiated carcinomas and two malignant carcinoids were labelled as adenocarcinoma and composite tumor respectively. Positive reactivity with CEA and alcian blue PAS and absence of AFP helped in differentiating one giant cell carcinoma from hepatocellular carcinoma. No definite marker could be identified in one case of malignant mesenchymal tumor. Histochemistry and immunohistochemistry also helped in confirming the diagnosis of three cases of carcinoma in situ, one of malignant carcinoid and three of clear cell carcinoma.
Sujets)
Adulte , Sujet âgé , Antigènes néoplasiques/métabolisme , Femelle , Tumeurs de la vésicule biliaire/diagnostic , Histocytochimie , Humains , Mâle , Adulte d'âge moyen , PhénotypeRésumé
The proliferative activity of human gastric carcinoma was measured by means of in vitro incorporation of the thymidine analogue, 5-bromo-2'-deoxyuridine (BrdU), into the newly-synthesized DNA of fresh tumors and immunohistochemical staining of proliferating cell nuclear antigen (PCNA) using avidin-biotin peroxidase method. Eighty-two cases of surgically resected human gastric carcinomas consisting of 18 various histologic types were subjected to study. The mean BrdU labelling index (LI) and PCNA LI were 22.9% and 39.1%, respectively. The correlation between BrdU LI and PCNA LI was statistically significant (correlation coefficient mu = 0.61334, p = 0.0001). We concluded that immunohistochemical staining for PCNA may become a practical method instead of in vitro or in vivo BrdU labeling to assess the proliferation fraction of the gastric cancer patient.