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1.
Front Oncol ; 13: 1160239, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37546427

RESUMEN

Locally aggressive mesenchymal tumors comprise a heterogeneous group of soft tissue and bone tumors with intermediate histology, incompletely understood biology, and highly variable natural history. Despite having a limited to absent ability to metastasize and excellent survival prognosis, locally aggressive mesenchymal tumors can be symptomatic, require prolonged and repeat treatments including surgery and chemotherapy, and can severely impact patients' quality of life. The management of locally aggressive tumors has evolved over the years with a focus on minimizing morbid treatments. Extensive oncologic surgeries and radiation are pillars of care for high grade sarcomas, however, play a more limited role in management of locally aggressive mesenchymal tumors, due to propensity for local recurrence despite resection, and the risk of transformation to a higher-grade entity following radiation. Patients should ideally be evaluated in specialized sarcoma centers that can coordinate complex multimodal decision-making, taking into consideration the individual patient's clinical presentation and history, as well as any available prognostic factors into customizing therapy. In this review, we aim to discuss the biology, clinical management, and future treatment frontiers for three representative locally aggressive mesenchymal tumors: desmoid-type fibromatosis (DF), tenosynovial giant cell tumor (TSGCT) and giant cell tumor of bone (GCTB). These entities challenge clinicians with their unpredictable behavior and responses to treatment, and still lack a well-defined standard of care despite recent progress with newly approved or promising experimental drugs.

2.
Clin Cancer Res ; 29(7): 1163-1166, 2023 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-36692840

RESUMEN

A recent randomized phase II study of sunitinib or cediranib in alveolar soft part sarcoma established benchmark activity for commonly used tyrosine kinase inhibitors (TKI). The impact of TKIs, as well as immunotherapy, has redefined treatment paradigms and greatly improved outcomes for this historically dismal sarcoma. See related article by Nguyen et al., p. 1200.


Asunto(s)
Antineoplásicos , Sarcoma de Parte Blanda Alveolar , Humanos , Sarcoma de Parte Blanda Alveolar/tratamiento farmacológico , Sunitinib/uso terapéutico , Antineoplásicos/uso terapéutico , Quinazolinas/uso terapéutico
3.
Pediatr Blood Cancer ; 69(2): e29442, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34767314

RESUMEN

Bone tumors are a group of histologically diverse diseases that occur across all ages. Two of the commonest, osteosarcoma (OS) and Ewing sarcoma (ES), are regarded as characteristic adolescent and young adult (AYA) cancers with an incidence peak in AYAs. They are curable for some but associated with unacceptably high rates of treatment failure and morbidity. The introduction of effective new therapeutics for bone sarcomas is slow, and to date, complex biology has been insufficiently characterized to allow more rapid therapeutic exploitation. This review focuses on current standards of care, recent advances that have or may soon change that standard of care and challenges to the expert clinical research community that we suggest must be met.


Asunto(s)
Neoplasias Óseas , Osteosarcoma , Sarcoma de Ewing , Sarcoma , Adolescente , Neoplasias Óseas/patología , Humanos , Osteosarcoma/patología , Sarcoma/tratamiento farmacológico , Sarcoma de Ewing/patología , Adulto Joven
4.
Cancers (Basel) ; 12(8)2020 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-32823999

RESUMEN

Sarcomas are rare cancers with a spectrum of clinical needs and outcomes. We investigated care experiences and health-related quality of life (HRQoL) in sarcoma patients during the COVID-19 pandemic. Patients with appointments during the first two months of the UK lockdown were invited to complete a survey. Questions included views on care modifications, COVID-19 worry and psychosocial impact, and EORTC-QLQ-C30 items. 350 patients completed the survey; median age 58 (16-92) years. Care modifications included telemedicine (74%) and postponement of appointments (34%), scans (34%) or treatment (10%). Most felt the quality of care was not affected (72%), however, social life (87%) and emotional wellbeing (41%) were affected. Worry about COVID-19 infection was moderately high (mean 5.8/10) and significantly related to higher cancer-related worry; associated with lower emotional functioning irrespective of treatment intent. Curative patients (44%) with low resilient coping scores had significantly higher COVID-19 worry. Patients who did not know their treatment intent (22%) had significantly higher COVID-19 worry and insomnia. In summary, care experiences were generally positive; however, cancer-related worry, low resilient coping and uncertainty about treatment intent were associated with COVID-19 worry. These patients may benefit from additional psychological support during the pandemic and beyond.

5.
Int J Surg Case Rep ; 4(1): 7-10, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23088904

RESUMEN

INTRODUCTION: The peritoneum is one of the most common sites of distant gastrointestinal stromal tumor (GIST) metastases. In particular, GIST arising from the small intestine with resected minimal synchronous macroscopic peritoneal carcinomatosis or with primary tumor rupture has a higher risk of developing peritoneal recurrence. Current clinical practice does not envisage second-look surgery in GIST patients at high risk of developing peritoneal recurrence, and no literature data are available. PRESENTATION OF CASE: We describe a 45-year-old woman who underwent emergency surgical resection of jejunal GIST presenting with spontaneous tumor rupture, synchronous ovarian and minimal macroscopic peritoneal involvement, and subsequent second-look surgery after 13 months of imatinib treatment. DISCUSSION: Second-look surgery confirmed a 2.6cm lesion close to the mesenteric border of the fourth jejunal loop, and 11 peritoneal lesions with a macroscopic necrotic aspect related to treatment response. After conversion to an open procedure, a segmental jejunal resection was performed with removal of all peritoneal lesions and macroscopic radical cytoreduction. CONCLUSION: Second-look surgery in selected GIST patients may be performed after at least 12 months of medical treatment with tyrosine-kinase inhibitors to identify those patients with limited peritoneal disease not disclosed by instrumental imaging who could undergo radical cytoreduction of peritoneal lesions.

6.
Oncol Lett ; 3(3): 677-681, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22740975

RESUMEN

Large-scale studies have demonstrated that continuative treatment in advanced and adjuvant settings results in a gain-of-survival. However, the discontinuation, and the duration of treatment in disease-free patients who have undergone radical surgical resection of metastases from gastrointestinal stromal tumours (GISTs) have yet to be evaluated. We retrospectively reviewed 40 patients with advanced and recurrent GIST, included in our GIST database, focusing on patients (5 males and 2 females; median age 56 years) who continued medical treatment following radical surgical resection of metastatic lesions. Seven out of 40 patients underwent surgery and continued medical treatment following radical surgical resection of metastatic lesions. The duration of adjuvant therapy was 3, 12, 16, 24, 35, 37 and 52 months, respectively, with a median of 26 months. No patients discontinued therapy and all were disease-free at the final CT-scan evaluation. Considering that the discontinuation of imatinib in responding patients with advanced GIST (even in complete remission) results in a rapid high risk of progression, and a short adjuvant therapy results in a shorter disease-free and overall survival in high-risk GIST patients, it is also likely that treatment should not be discontinued in this setting. However, large-scale studies are required to better assess the optimal duration of treatment, particularly after 5 years, by focusing on the identification of predictive factors for the selection of patients who may benefit from a prolonged or lifelong imatinib treatment.

7.
Med Oncol ; 29(1): 144-50, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21258878

RESUMEN

In practice, relapses of gastrointestinal stromal tumours after long time of surgical resection occur. However, few published data are available for duration, intensity and imaging sources of follow-up in radically excised patients with localized disease. Therefore, every single institution chooses the surveillance schedule according to its experience. The aim of this study was to describe the late recurrences of disease 5 years after the primary tumour's excision in a series of patients with recurrent GIST from our institution. We retrospectively reviewed 42 patients with "recurrent" GIST, collected since 2001. Ten patients were always followed at our institution, and 32 patients came to our attention at the time of recurrence. The analysed series were divided into two groups: patients who developed recurrence before 5 years and patients who developed recurrence 5 years after the primary tumour's excision. Among 42 patients, 36 patients developed the recurrence within 5 years of the primary tumour excision, whereas 6 patients developed the recurrence 5 years after primary tumour excision diagnosed during follow-up or casually for other reasons. All patients had distant recurrence, involving liver and peritoneum, whereas no local relapse was observed. These patients were heterogeneous in primary tumour site, risk classification and molecular analysis. Duration of the follow-up for radically excised patients with GIST remains still unsettled; however, the integration of every clinical, pathological and molecular parameter is essential to optimize the duration and intensity of the follow-up for each single patient.


Asunto(s)
Tumores del Estroma Gastrointestinal/patología , Recurrencia Local de Neoplasia/patología , Adulto , Anciano , Anciano de 80 o más Años , Análisis Mutacional de ADN , Femenino , Estudios de Seguimiento , Tumores del Estroma Gastrointestinal/genética , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Proteínas Proto-Oncogénicas c-kit/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Estudios Retrospectivos , Factores de Riesgo
8.
Histopathology ; 59(6): 1071-80, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22175887

RESUMEN

AIMS: To compare the genomic signatures of wild-type (WT) and mutated GISTs and the murine interstitial cells of Cajal (ICCs) to find markers of cell differentiation and other functions that may identify cells that give rise to WT tumours. METHODS AND RESULTS: We analysed the gene expression profiles of a total of 30 tumour samples (four WT GISTs and 26 mutated GISTs), selected the genes most differentially expressed (P < 0.001:448 probe sets) and validated these results by quantitative polymerase chain reaction (PCR) and immunohistochemistry. In addition, we conducted a meta-analysis merging data from human GISTs with a genomic data set from murine ICCs. The gene expression profiles of WT and mutated GISTs differed profoundly, especially in the expression of those genes restricted primarily to neural tissues. We found that mature ICCs are more similar to mutated GISTs than WT GISTs. CONCLUSIONS: WT GISTs have different genomic profiles from both mutated GISTs and murine mature ICCs. Considering that IGF1R expression is common to both WT GISTs and putative precursor ICCs, this study suggests that WT GISTs may derive either from ICCs at a different step of differentiation or from a different cell of origin.


Asunto(s)
Biomarcadores de Tumor/análisis , Tumores del Estroma Gastrointestinal/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Células Intersticiales de Cajal/patología , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Factor de Células Madre/genética , Adulto , Anciano , Anciano de 80 o más Años , Animales , Biomarcadores de Tumor/genética , Análisis Mutacional de ADN , Tumores del Estroma Gastrointestinal/patología , Humanos , Inmunohistoquímica , Células Intersticiales de Cajal/metabolismo , Ratones , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa
9.
Rare Tumors ; 3(2): e17, 2011 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-21769316

RESUMEN

Gastrointestinal stromal tumors (GISTs) are rare, but represent the most common mesenchymal neoplasms of the gastrointestinal tract. Tumor resection is the treatment of choice for localized disease. Tyrosine kinase inhibitors (imatinib, sunitinib) are the standard therapy for metastatic or unresectable GISTs. GISTs usually metastasize to the liver and peritoneum. Bone metastases are uncommon. We describe three cases of bone metastases in patients with advanced GISTs: two women (82 and 54 years of age), and one man (62 years of age). Bones metastases involved the spine, pelvis and ribs in one patient, multiple vertebral bodies and pelvis in one, and the spine and iliac wings in the third case. The lesions presented a lytic pattern in all cases. Two patients presented with multiple bone metastases at the time of initial diagnosis and one patient after seven years during the follow-up period. This report describes the diagnosis and treatment of the lesions and may help clinicians to manage bones metastases in GIST patients.

10.
J Transl Med ; 9: 75, 2011 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-21605429

RESUMEN

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Most GIST harbor a mutation affecting either the KIT or PDGFRA genes, whereas a small subgroup of tumors is wild type for mutations.Mutation of tyrosine kinase receptors is a mechanism of drug resistance that can occur either at the beginning of treatment (primary resistance) or during the course of therapy (secondary resistance). In addition, mutational status can predict the response to treatment with tyrosine kinase inhibitors, but the role of mutational status as a prognostic factor remains controversial.Evidence of a potential role of mutational status as a prognostic factor has emerged over the past decade. The presence of KIT exon 11 insertion/deletion involving either one or both Trp557-Lys558 amino acids correlates with a poorer clinical outcome if compared to patients with tumors wild type for KIT exon 11 mutations. A malignant clinical behavior has also been documented for KIT exon 13 and KIT exon 9 mutant GIST. Patients with GIST harboring a PDGFRA mutation seem to have a better prognosis than the others.The aim of this paper is to review the clinical significance of tyrosine kinase mutational status.


Asunto(s)
Tumores del Estroma Gastrointestinal/enzimología , Tumores del Estroma Gastrointestinal/genética , Proteínas Proto-Oncogénicas c-kit/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Análisis Mutacional de ADN , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Humanos , Pronóstico
11.
Expert Opin Ther Targets ; 15(7): 803-15, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21385119

RESUMEN

INTRODUCTION: The biological complexity of gastrointestinal stromal tumors (GISTs) and the concomitant increase in patients' life expectancy have enhanced the need for new therapeutic options to overcome the development of primary and secondary resistance to tyrosine kinase inhibitors. Aided by more sophisticated molecular biology techniques, researchers have recently sought to identify new therapeutic targets with a defined role in GISTs pathogenesis and a potential application in clinical practice. AREAS COVERED: The first aim of this review is to describe new targets and drugs in GISTs, alone or in combination, both in pre-clinical and clinical settings. The second aim is to discuss the criticism in this field, the role of molecular biology, and future perspectives in light of the recent development of more sophisticated whole-genomic technologies. EXPERT OPINION: Several targets involved in GIST pathogenesis have been identified and novel biological drugs have recently been developed, offering new treatment options in the scenario of GIST therapy. However, the identification of new therapeutic targets represents a long process and requires a global overview of the problem and a multi-step approach to convert an initial intuition or casual finding into a systematic analytical process.


Asunto(s)
Antineoplásicos/farmacología , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-kit/efectos de los fármacos , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/efectos de los fármacos , Antineoplásicos/uso terapéutico , Humanos
12.
Oncol Rep ; 25(1): 113-20, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21109965

RESUMEN

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that most frequently arise in the gastrointestinal tract. The liver and peritoneum are common sites of distant GIST lesions, whereas lung metastases are infrequent, accounting for 7% of all lesions. The clinical significance of these metastases remains unknown. Although lung metastases are relatively rare in the natural history of GIST, they may become more prevalent due to increased patient life expectancy. The present report describes four patients with GIST who had lung metastases. Two were female (54 and 28 years of age), and two were male (64 and 44 years of age). The primary GISTs were localized in the stomach in two patients and in the small intestine in the other two patients. Three patients presented with multiple lung lesions and one presented with one lung lesion. Lung metastases were present at the time of initial diagnosis in one patients, and were observed during the follow-up period in the other three. In this report we detail the clinical presentation and radiological features of the lung lesions as observed by computed tomography (CT) and computed tomography/ positron emission tomography (CT/PET). We describe each patient's clinical history and treatment which included surgery and the tyrosine kinase inhibitors, imatinib and sunitinib, and the novel therapy, nilotinib. Moreover, we discuss some biological aspects of this relatively rare occurrence and the resulting clinical implications. These findings may help clinicians to manage lung metastases arising from GISTs in future.


Asunto(s)
Tumores del Estroma Gastrointestinal/patología , Neoplasias Pulmonares/secundario , Adulto , Femenino , Tumores del Estroma Gastrointestinal/diagnóstico por imagen , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X
13.
Tumori ; 96(2): 219-28, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20572577

RESUMEN

AIMS AND BACKGROUND: Even though the standard treatment of patients affected by gastrointestinal stromal tumors has been well defined by clinical trials and clinical guidelines, in practice it may be different from those proposed in the literature. This paper reports and comments on a critical picture of the management of patients with gastrointestinal stromal tumors who received at least one treatment before arriving at our GIST Study Group. METHODS AND STUDY DESIGN: Attention was focused on 60 patients from various hospitals. Retrospective clinical data were recorded and analyzed with the "event tree" model, which describes the algorithm of all treatment options that each patient received before. Responses from first to fourth line of therapy, time to progression, and survival analysis were also analyzed. RESULTS: Starting from the diagnosis of disease, seven possible therapeutic event trees were identified: one for 7 unresectable patients and six different trees for 53 recurred patients who initially underwent surgery. The event trees describe the multitude of different treatments that patients with gastrointestinal stromal tumors received during the course of their disease. CONCLUSIONS: In clinical practice, the treatment of patients affected by gastrointestinal stromal tumor is still difficult, and the published recommendations often do not cover all therapeutic decisions for all clinical presentations of disease. Multidisciplinary dedicated teams are needed to offer the possibility to receive appropriate surgery and innovative medical therapies. The formation of formalized GIST Units is in progress in several parts of Italy. The GIST Units can be organized in a network to facilitate discussion and agreement for the wide variety of clinical presentation.


Asunto(s)
Toma de Decisiones , Tumores del Estroma Gastrointestinal/terapia , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Tumores del Estroma Gastrointestinal/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
14.
Lab Invest ; 90(9): 1285-94, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20548289

RESUMEN

In addition to KIT and PDGFRA mutations, sequential accumulation of other genetic events is involved in the development and progression of gastrointestinal stromal tumors (GISTs). Until recently, the significance of these other alterations has not been thoroughly investigated. We report the first study that integrates gene expression profiling and high-resolution genomic copy number analyses in GIST. Fresh tissue specimens from 25 patients with GIST were collected, and gene expression profiling and high-resolution genomic copy number analyses were performed, using Affymetrix U133Plus and SNP array 6.0. We found that all 21 mutant GIST patients showed both macroscopic cytogenetic alterations and cryptic microdeletions or amplifications, whereas 75% (three of four) of wild-type patients with GIST did not show genomic imbalances. The most frequently observed chromosomal alterations in patients with mutant GIST included 14q complete or partial deletion (17 of 25), 1p deletion (14 of 25) and 22q deletion (10 of 25). Genetic targets of the chromosomal aberrations were selected by integrated analysis of copy number and gene expression data. We detected the involvement of known oncogenes and tumor suppressors including KRAS in chr 12p amplification and KIF1B, PPM1A, NF2 in chr 1p, 14q and 22p deletions, respectively. The genomic segment most frequently altered in mutated samples was the 14q23.1 region, which contains potentially novel tumor suppressors, including DAAM1, RTN1 and DACT1. siRNA-mediated RTN1 downregulation showed evidence for the potential role in GIST pathogenesis. The combination of gene expression profiling and high-resolution genomic copy number analysis offers a detailed molecular portrait of GISTs, providing an essential comprehensive knowledge necessary to guide the discovery of novel target genes involved in tumor development and progression.


Asunto(s)
Tumores del Estroma Gastrointestinal , Perfilación de la Expresión Génica/métodos , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Aberraciones Cromosómicas , Cromosomas Humanos Par 22/metabolismo , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/metabolismo , Tumores del Estroma Gastrointestinal/patología , Expresión Génica , Genes ras , Genoma , Genotipo , Humanos , Análisis por Micromatrices , Proteínas de Microfilamentos , Mutación , Oncogenes , Polimorfismo de Nucleótido Simple , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Proteínas de Unión al GTP rho
15.
Int J Cancer ; 125(12): 2991-4, 2009 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-19672856

RESUMEN

Aberrations of the Insulin-like Growth Factor (IGF) system have been found in association with a variety of cancer types. The potential role of IGF1R has been postulated in a small subset of GISTs, but until now the implications of its aberrations have not been defined. The aim of the study was to examine the IGF1R status in patients with gastric GIST in regard to KIT and PDGFRA genotype. Fresh resection specimens were collected from 8 primary tumours [2 wild-type (WT) and 6 mutant cases]. IGF1R was studied as gene expression profiling with Affymetrix GeneChip HG-U133Plus 2.0 arrays and as genomic copy number with SNP array analysis Affymetrix Genome Wide Human SNP 6.0 arrays, and at protein level with western blotting (WB) and immunohistochemistry (IHC). The unsupervised analysis of gene expression profiling of our patients merged with a data set from gastric GISTs identified 2 patients out of 8 with different expression of IGF1R. The data were confirmed by WB and IHC. In particular, IGF1R was upregulated in 2 young patients (<30-years old), who had both WT disease and metastases at diagnosis. The SNP array analysis showed that none of the tumours had IGF1R amplification. GISTs are characterized by abnormalities of the KIT and PDGFRA receptors that affect prognosis and response to tyrosine kinase inhibitors. Both young adult with WT GIST had the over-expression of IGF1R at mRNA and protein level. These results further confirm the hypothesis that IGF1R may be a potential therapeutic target in GISTs lacking KIT and PDGFRA mutations.


Asunto(s)
Tumores del Estroma Gastrointestinal/metabolismo , Amplificación de Genes , Mutación/genética , Polimorfismo de Nucleótido Simple/genética , Receptor IGF Tipo 1/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Western Blotting , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/secundario , Perfilación de la Expresión Génica , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas Proto-Oncogénicas c-kit/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptor IGF Tipo 1/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
16.
Tumori ; 95(3): 382-4, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19688982

RESUMEN

Sunitinib is an oral multitargeted tyrosine kinase inhibitor with antiangiogenic properties used for treatment of renal cell carcinoma and gastrointestinal stromal tumors at a dose of 50 mg/day consecutively for 4 weeks followed by 2 weeks off per cycle. At present, no data are available on the early prediction of sunitinib response in renal cell carcinoma. We report a clinical case of a patient with metastatic renal cell carcinoma diagnosed with 11C-acetate PET and conventional CT and treated with sunitinib. Partial and complete remission documented by CT was preceded by early functional tumor inhibition shown by 11C-acetate-PET after only 14 days of therapy. This case report highlights some interesting points related to the potential role of a novel non-FDG PET tracer, 11C-acetate, in the early prediction of the response to targeted therapies in metastatic renal cell carcinoma.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/secundario , Indoles/uso terapéutico , Neoplasias Renales/patología , Neoplasias Hepáticas/tratamiento farmacológico , Tomografía de Emisión de Positrones , Pirroles/uso terapéutico , Neoplasias de las Glándulas Suprarrenales/secundario , Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía , Anciano , Inhibidores de la Angiogénesis/uso terapéutico , Radioisótopos de Carbono , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/cirugía , Femenino , Fluorodesoxiglucosa F18 , Humanos , Neoplasias Renales/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Nefrectomía , Neoplasias Pancreáticas/secundario , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía , Tomografía de Emisión de Positrones/métodos , Valor Predictivo de las Pruebas , Inhibidores de Proteínas Quinasas/uso terapéutico , Sunitinib , Resultado del Tratamiento
17.
Oncol Rep ; 21(6): 1359-66, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19424610

RESUMEN

Treatment of patients affected by advanced or inoperable GIST was revolutionized by the use of the tyrosine kinase inhibitors. Despite the fact that most patients have a good durable response of disease, they develop a resistance to treatments after a median time of 24 months. The acquired resistance is an emerging aspect in medical oncology especially in the era of target therapies. The aim of this review is to report all known mechanisms of secondary resistance to tyrosine kinase inhibitors and to highlight their clinical implications. In general, they may be divided in mechanisms related to the acquisition of new molecular abnormalities associated to KIT and PDGFRA receptor signalling pathway, such as the loss of KIT expression, the genomic amplification of KIT, the activation of an alternative downstream signalling pathways such as AKT/mTOR and the acquisition of new receptor mutations, and other mechanisms different to KIT/PDGFRA receptors. Future research perspectives on target therapy and early resistance evaluation are also discussed.


Asunto(s)
Antineoplásicos/uso terapéutico , Resistencia a Antineoplásicos , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Animales , Resistencia a Antineoplásicos/genética , Tumores del Estroma Gastrointestinal/enzimología , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/patología , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Mutación , Proteínas Tirosina Quinasas/genética , Proteínas Tirosina Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-kit/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Factores de Tiempo , Insuficiencia del Tratamiento
19.
Cancer Chemother Pharmacol ; 64(1): 189-93, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19151974

RESUMEN

PURPOSE: We investigated the efficacy and toxicity of metronomic capecitabine administered at a fixed dose of 1,000 mg daily in three elderly or poor performance status patients with advanced colorectal cancer (CRC) and gastric cancer. METHODS: In this study a pretreated advanced CRC patient (patient 1), a not previously treated advanced gastric cancer patient (patient 2), and a not previously treated advanced rectal cancer patient (patient 3) were given metronomic capecitabine administered at a fixed dose of 1,000 mg daily (day 1-28 continuously). The efficacy was evaluated every 3 months by instrumental evaluation and the treatment was continued until progression of disease or toxicity. RESULTS: A stable disease was observed in all three patients. The duration of treatment was above 3 months and no major toxicities occurred. CONCLUSIONS: Our results indicate that metronomic capecitabine may be considered a safe and valid treatment option for advanced CRC and gastric cancer patients, both after failure of previous lines of chemotherapy or in front-line when standard chemotherapy is contraindicated, especially when the aim of medical treatment is to achieve disease control and to arrest tumour growth without affecting the patient's quality of life. Nevertheless, further clinical studies, as well as a greater clinical experience are required in order to better define the role of this strategy in medical oncology.


Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Fluorouracilo/análogos & derivados , Neoplasias Gástricas/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/efectos adversos , Capecitabina , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Estudios de Seguimiento , Humanos , Neoplasias del Recto/tratamiento farmacológico , Resultado del Tratamiento
20.
Cancer Treat Rev ; 35(3): 201-9, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19081199

RESUMEN

Nowadays molecular biology represents one of the most interesting topics in medical oncology, because it provides a global and detailed view on the molecular changes involved in tumour progression, leading to a better understanding of the carcinogenesis process, to discovering new prognostic markers and novel therapeutic targets. The gene expression profiling analysis with microarray technology has shown a great potential in cancer research and in medical oncology, mapping simultaneously the expression of thousands of genes in a single tumour sample and giving a measurement of articulated genes expression patterns. Colorectal cancer represents a wide and exciting area of research for molecular biology, due to the growing need of a molecular classification as well as prognostic and predictive molecular factors that may guide oncologists in patient's clinical management. The aim of this review is to analyze the state of art of gene expression profile in colorectal cancer using microarrays technologies and to explore some perspectives in this research field.


Asunto(s)
Adenocarcinoma/genética , Neoplasias Colorrectales/genética , Perfilación de la Expresión Génica , Proteínas de Neoplasias/análisis , Análisis de Secuencia por Matrices de Oligonucleótidos , Adenocarcinoma/química , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/secundario , Antineoplásicos/uso terapéutico , Transformación Celular Neoplásica , Neoplasias Colorrectales/química , Neoplasias Colorrectales/tratamiento farmacológico , ADN Complementario/análisis , ADN de Neoplasias/genética , Progresión de la Enfermedad , Monitoreo de Drogas/métodos , Femenino , Predicción , Humanos , Neoplasias Hepáticas/secundario , Masculino , Oncología Médica/métodos , Pronóstico , ARN Mensajero/análisis , ARN Mensajero/biosíntesis , ARN Mensajero/genética , ARN Neoplásico/análisis , ARN Neoplásico/biosíntesis , ARN Neoplásico/genética , Resultado del Tratamiento
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