RESUMO
Pheochromocytomas and paragangliomas (PPGL) are neuroendocrine tumors characterized by the excessive production of catecholamines. This study aims to describe the clinical characteristics of PPGL cases in Argentina over recent decades. A multicenter retrospective cross-sectional analysis was carried out using a database comprising both pediatric and adult patients with confirmed PPGL diagnoses based on pathological reports. A cohort of 486 patients with PPGL was recruited. Women represent 58.4% of the patients, with a mean age of 38.3 years old at the time of diagnosis and 15.2% of the patients were under the age of 18. Hypertension, as well as classic signs and symptoms, were present in 80.9% of the patients. The adrenal incidentaloma, as a mode of presentation, increased in the last two decades rising from 3.9% (1953-2000) to 21.8% (2001-2022), p<0.001. Most tumors were located within the adrenal glands, accounting 83.0% of the cases, with bilateral occurrences noted in 20.0%. The median tumor size was 4.8cm. Local recurrence and metastases were observed in 10.9% and 12.2%. Out of 412 patients, 87.0% exhibited urinary excretion elevation of catecholamines and/or their metabolites. Furthermore, 148 patients, representing 30.4% of the study population, displayed a distinct genetic profile indicative of hereditary syndromes. The distribution of hereditary syndromes revealed that MEN2, VHL, and PGL4 constituted the most prevalent syndromes. This population-based study, spanning seven decades, offers valuable insights into the demographic and clinical characteristics of PPGL patients in Argentina.
Assuntos
Neoplasias das Glândulas Suprarrenais , Bases de Dados Factuais , Paraganglioma , Feocromocitoma , Humanos , Feocromocitoma/patologia , Feocromocitoma/epidemiologia , Argentina , Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/patologia , Feminino , Masculino , Estudos Retrospectivos , Adulto , Paraganglioma/patologia , Estudos Transversais , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Criança , Idoso , Recidiva Local de Neoplasia/epidemiologia , Pré-Escolar , Hipertensão/epidemiologiaRESUMO
BACKGROUND: This article describes and compares approved targeted therapies and the newer immunotherapy agents. MATERIALS AND METHODS: This article especially performs an in-depth review of currently available data for tivozanib, explaining its mechanism of action, its safety profile and its role as an efficacy drug in the management of renal cancer. RESULTS: Despite the fact that the treatment of advanced RCC has been dramatically modified in recent years, durable remissions are scarce and it remains a lethal disease. For first- and second-line therapy, there is now growing evidence to guide the selection of the appropriate treatment. CONCLUSIONS: Several TKIs are standard of care at different settings. Among those approved TKIs, tivozanib has similar efficacy than others with a better safety profile. The use of prognostic factors is critical to the selection of optimal therapy.
Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Ensaios Clínicos como Assunto , Consenso , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Metástase NeoplásicaRESUMO
INTRODUCCIÓN: Problema de Investigación: La parálisis facial periférica es una de las causas más frecuentes de deformidad estética facial y alteraciones funcionales, entre los factores de riesgo de parálisis facial está la hipertensión arterial. OBJETIVO: Determinar la asociación entre hipertensión arterial y Parálisis Facial Periférica en pacientes que acuden a Consulta Externa del Servicio de Medicina Física y Rehabilitación del Hospital de Clínicas Universitario durante la gestión 2013 a 2016 DISEÑO METODOLÓGICO: El presente estudio es un estudio analítico de casos y controles, realizado en pacientes que acuden a Consulta Externa del Servicio de Medicina Física y Rehabilitación del Hospital Clínicas Universitario de enero de 2008 a diciembre de 2010. En total se estudiaron 122 pacientes con parálisis facial leve, moderada y severa, en diferentes edades y con distintos factores de riesgo, estos datos fueron estratificados por la Escala de House Brackman. Los casos fueron pacientes con parálisis facial severa y los controles pacientes con parálisis facial moderada y leve. RESULTADOS: Se encontró asociación positiva entre la hipertensión arterial y la parálisis facial severa (p=0.025), triplicando la hipertensión arterial el riesgo de padecer una parálisis facial severa (OR=3.3), en todo los grupos de edad. CONCLUSIÓN: La hipertensión arterial sistémica es un factor de riesgo de parálisis facial severa, independientemente de la edad de la persona.
INTRODUCTION: Research Problem: Peripheral facial paralysis is one of the most frequent causes of facial aesthetic deformity and functional alterations, among the risk factors for facial paralysis is high blood pressure. OBJECTIVE: To determine the association between arterial hypertension and Peripheral Facial Paralysis in patients attending the External Consultation of the Physical Medicine and Rehabilitation Service of the Hospital de Clínicas Universitario during the TERM 2013 to 2016 METHODOLOGICAL DESIGN: The present study is an analytical study of cases and controls, carried out in patients who attend the Outpatient Service of Physical Medicine and Rehabilitation of the Hospital Clínicas Universitario from January 2008 to December 2010. In total, 122 patients were studied. Mild, moderate and severe facial paralysis, at different ages and with different risk factors, these data was stratified by the House Brackman Scale. The cases were patients with severe facial paralysis and the controls patients with moderate and mild facial paralysis. RESULTS: A positive association was found between arterial hypertension and severe facial paralysis (p = 0.025), tripling the arterial hypertension the risk of suffering a severe facial paralysis (OR = 3.3), in all the age groups. CONCLUSION: Systemic arterial hypertension is a risk factor for severe facial paralysis, regardless of the age of the person.
Assuntos
Humanos , Nervo Facial , Paralisia Facial/reabilitação , Hipertensão , Serviços de ReabilitaçãoRESUMO
The immune system regulates angiogenesis in cancer by way of both pro- and antiangiogenic activities. A bidirectional link between angiogenesis and the immune system has been clearly demonstrated. Most antiangiogenic molecules do not inhibit only VEGF signaling pathways but also other pathways which may affect immune system. Understanding of the role of these pathways in the regulation of immunosuppressive mechanisms by way of specific inhibitors is growing. Renal cell carcinoma (RCC) is an immunogenic tumor in which angiogenesis and immunosuppression work hand in hand, and its growth is associated with impaired antitumor immunity. Given the antitumor activity of selected TKIs in metastatic RCC (mRCC), it seems relevant to assess their effect on the immune system. The confirmation that TKIs improve cell cytokine response in mRCC provides a basis for the rational combination and sequential treatment of TKIs and immunotherapy.
Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/imunologia , Imunoterapia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/imunologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , HumanosRESUMO
Advanced prostate cancer is an androgen-dependent disease for which the initial treatment is an androgen deprivation maneuver. However, some primary resistances to hormonal treatment occur with increasing incidence throughout the evolution of the disease. The taxanes, docetaxel and cabazitaxel, exert their action at multiple levels at the tumor cell: besides inhibiting the mitosis and inducing the cell death, they induce the nuclear accumulation of FOXO1, a potent nuclear factor that acts against the activation of androgen receptor inhibiting the transcription of AR-V7 variant associated with the development of resistances to abiraterone and enzalutamide. Docetaxel, as first-line therapy, and cabazitaxel, as second-line therapy, have demonstrated to increase the survival in castration-resistant prostate cancer. The results from last studies either on high-risk localized disease or on androgen-sensitive tumors demonstrate the increasing role of taxanes at earlier states of prostate cancer.
Assuntos
Neoplasias da Próstata/tratamento farmacológico , Taxoides/uso terapêutico , Animais , Humanos , MasculinoRESUMO
We performed a literature search that shed light on the signaling pathways involved in the sorafenib activity as first- or subsequent-line treatment, taking into account its toxicity profile. Sorafenib appears to have better tolerability when compared with other agents in the same indication. Cross-resistance between tyrosine kinase inhibitors (TKIs) may be limited, even after failure with a previous VEGFR inhibitor, but the optimal sequence with TKIs remains to be determined. Randomized trials of second-line treatment options have showed either modest or no differences in terms of progression-free and overall survival (OS). Direct comparison between sorafenib and axitinib demonstrated differences in terms of PFS in favor of axitinib, but not in terms of OS as second-line treatment. In contrast, a phase III study showed a benefit in OS, favoring sorafenib when compared with temsirolimus. In conclusion, after using other VEGF inhibitor such as sunitinib, sorafenib is active and safe for the treatment of patients with advanced or metastatic RCC.
Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Carcinoma de Células Renais/mortalidade , Ensaios Clínicos como Assunto , Humanos , Neoplasias Renais/mortalidade , Niacinamida/uso terapêutico , Terapia de Salvação , Sorafenibe , Taxa de Sobrevida , Resultado do TratamentoRESUMO
INTRODUCTION: Kidney tumours are frequently characterised by hypoxic conditions due to a local imbalance between oxygen (O2) supply and consumption. Hif1-α regulates angiogenesis, tumour growth, tumour progression, metastatic spread, and glucose metabolism by acting as a transcription factor for relevant genes. Here, we describe an immunohistochemical study of Hif1-α, a comprehensive computational study of Hif1-α interacting proteins (HIPs), an analysis correlating expression levels of Hif1-α with upstream and downstream proteins, and an analysis of the utility of Hif1-α for prognosis in a cohort of patients with renal cell carcinoma. MATERIALS AND METHODS: The patient cohort included 80 patients. For immunohistochemistry evaluation, tissue microarrays were constructed. The IntAct, MINT, and BOND databases were used for the HIP approach. The Kruskal-Wallis test was used for comparing protein expression with pathology measurements. Correlation was expressed as the Pearson coefficient. RESULTS: Hif1-α expression correlates significantly with the "clear" histological subtype of renal cell carcinoma (p < 0.01). The samples with the worst prognoses related to the pathological variables analysed showed the highest levels of Hif1-α expression. Significant correlations were found with Bcl-2, CAIX, C-kit, EGFR, TGF-ß, proteins of the VEGF family, proteins related to differentiation (such as Notch1 and Notch3) and certain metabolic enzymes. Bioinformatic analysis suggested 45 evidence-based HIPs and 4 complexes involving protein Hif1-α. CONCLUSIONS: This work summarises the multifaceted role of Hif1-α in the pathology of renal cell carcinomas, and it identifies HIPs that could help provide mechanistic explanations for the different behaviours seen in tumours.
Assuntos
Carcinoma de Células Renais/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Renais/metabolismo , Mapeamento de Interação de Proteínas , Adulto , Idoso , Carcinoma de Células Renais/patologia , Estudos de Coortes , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Orthostatic hypotension (OH) is a risk factor for morbidity and mortality and one of the causes of non compliance to treatment among medicated hypertensive subjects. Our objective was to assess the prevalence of OH among treated hypertensive patients and its association with clinical characteristics and antihypertensive drug class. METHODS: This was a cross-sectional study in which we assessed the prevalence of OH, defined according to the American Autonomic Society and American Academy of Neurology guidelines, among adult treated hypertensive patients who performed a home blood pressure monitoring at our institution. We also determined the prevalence of OH according to age group (< 65, 65-79 and > 80), antihypertensive drug class, office and home hypertension control status. RESULTS: We included 302 medicated patients in the study. Mean age was 66.6 (+13.8), 67% were women. We found a 9.7% global prevalence of OH, which was significantly higher among older individuals (3.6% among patients < 65 years-old, 12.2% in the 65-79 year-old group and 16.7% among octogenarians, p = 0.02) and those who consumed alpha-blockers (75 vs. 8.5%, p < 0.01). Uncontrolled hypertensive patients at office and/or at home had also a significantly higher prevalence of OH: uncontrolled vs. controlled office blood pressure (BP), 14.3 vs. 6.5%, p = 0.03 and uncontrolled vs. controlled home BP, 15.1 vs. 6.6%, p = 0.02. Remarkably, 64% of patients with OH had their BP under control when considering office-standing BP. CONCLUSION: OH is a prevalent entity among treated hypertensive patients and systematic measurement of standing BP should be mandatory in the evaluation of these patients.
Assuntos
Hipertensão/tratamento farmacológico , Hipotensão Ortostática/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/classificação , Anti-Hipertensivos/uso terapêutico , Determinação da Pressão Arterial , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
Prokaryotes have developed multiple strategies to survive phage attack and invasive DNA. Recently, a novel genetic program denominated the CRISPR/Cas system was demonstrated to have a role in these biological processes providing genetic immunity. This defense mechanism is widespread in the Archaea and Bacteria, suggesting an ancient origin. In the last few years, progress has been made regarding the functionality of the CRISPR/Cas system; however, many basic aspects of the system remain unknown. For instance, there are few studies about the conditions and regulators involved in its transcriptional control. In this work, we analyzed the transcriptional organization of the CRISPR/Cas system as well as the positive and negative regulators involved in its genetic expression in Salmonella enterica serovar Typhi. The results obtained show that in S. Typhi the CRISPR/Cas system is a LeuO-dependent operon silenced by the global regulator LRP, in addition to the previously known nucleoid-associated protein H-NS; both LRP and H-NS bind upstream and downstream of the transcriptional start site of casA. In this study, relevant nucleotides of the casA regulatory region that mediate its LeuO transcriptional activation were identified. Interestingly, specific growth conditions (N-minimal medium) were found for the LeuO-independent expression of the CRISPR/Cas system in S. Typhi. Thus, our work provides evidence that there are multiple modulators involved in the genetic expression of this immune system in S. Typhi IMSS-1.
Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação Bacteriana da Expressão Gênica , Proteína Reguladora de Resposta a Leucina/metabolismo , Óperon , Salmonella typhi/genética , Fatores de Transcrição/metabolismo , Análise Mutacional de DNA , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Ligação Proteica , Análise de Sequência de DNA , Deleção de SequênciaRESUMO
An incomplete inhibition of the renin angiotensin aldosterone system (RAAS) may be responsible for the residual organ damage and event rate that still occur in spite of an apparent blood pressure control in patients with hypertension, diabetes, chronic kidney disease and heart failure treated with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Additional antiproteinuric effect in diabetic and non diabetic chronic kidney disease, and reduction in hospitalizations in patients with heart failure already receiving a single RAAS antagonist, has been achieved by incremental inhibition of the RAAS with dual therapy or uptitration of an individual agent above conventional dosages. However, the synergistic increase in plasma renin activity (PRA) and the angiotensin II escape could reduce the expected benefit obtained with dual therapy. Results from ONTARGET showing a lack of additional outcome benefit over monotherapy, with a concomitant increase risk of hyperkalemia, renal impairment, and hypotension, discourage the use of the ACEI/ARB combination in patients at high risk of cardiovascular events. This occured despite a lower albumin excretion in dual versus single RAAS blockade, indicating that an incremental antiproteinuric effect is not automatically translated into clinical outcome benefits. The efficacy and safety of ACEI/ARB combination versus monotherapy in patients with overt proteinuria is currently evaluated by LIRICO and VA NEPHRON-D clinical trials. The long lasting direct renin inhibitor aliskiren, acting at the first and rate limiting step of the RAAS cascade, prevents the reactive increase in PRA when combined with ACEIs, ARBs or diuretics. The ASPIRE HIGHER programme, involving more than 35,000 patients with hypertension, heart failure, kidney disease and diabetes, is currently evaluating the efficacy and safety of aliskiren on top of standard therapy. The clinical benefit of adding mineralocorticoid receptor blockers (MRBs) in the control of resistant hypertension, proteinuric kidney diseases, and prevention of mortality in patients with heart failure on top of conventional treatment, evidences the pathogenic role of inadequately suppressed aldosterone as a cause of suboptimal response to conventional RAAS inhibition. The present review will focus on the pathophysiological ground, and the evidence provided by clinical trials assessing the efficacy and safety of recent strategies for the prevention of cardiovascular events and target organ damage progression via enhanced RAAS inhibition.
Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Nefropatias/prevenção & controle , Doenças Cardiovasculares/etiologia , Humanos , Nefropatias/etiologia , Sistema Renina-Angiotensina/fisiologiaRESUMO
Epidemiological studies provided the first evidence that COX may be involved in the pathogenesis of cancer. In the process of carcinogenesis and in the route of intracellular signalling during carcinogenesis, COX-2 expression may be a universal phenomenon. In general, COX-2 is up-regulated throughout the tumorigenic process, from early hyperplasia to metastatic disease. COX-2 has been reported to be constitutively overexpressed in a variety of malignancies and is frequently constitutively elevated in prostate carcinoma. COX-2 was consistently overexpressed in premalignant lesions such as prostatic intraepithelial neoplasia, and carcinoma. Cases are described with evolution of proliferative inflammatory atrophy of the prostate and prostate carcinoma. The increase of evidence implicating COX-2 in cancer has stimulated clinical trials to investigate the efficacy of selective COX-2 inhibitors in individuals at risk for human cancer. Regarding prostate carcinoma there is much direct or indirect evidence to support the use of COX-2 inhibitors in this disease. Trials using these drugs in familial adenomatous polyposis (FAP) and other patients with a high risk of colorectal carcinoma are ongoing.
Assuntos
Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Neoplasias da Próstata/enzimologia , Humanos , Masculino , Transdução de SinaisRESUMO
Parathyroid carcinoma is a rare malignancy of the parathyroid glands, and is the cause of primary hyperparathyroidism in fewer than one percent of cases. Symptoms are mainly due to local compression or hypercalcaemia secondary to markedly elevated parathyroid hormone levels. A minority of patients remain asymptomatic. Mediastinal parathyroid cysts are infrequent and may or may not be functioning. We present an 84-year-old woman with a giant functioning cystic parathyroid carcinoma located in the middle mediastinum. We performed a thorough MEDLINE and LILACS database search on published cases of parathyroid carcinoma and functioning parathyroid cysts, and found no case report with identical features to the one presented here.
Assuntos
Hiperparatireoidismo Primário/diagnóstico , Cisto Mediastínico/diagnóstico , Neoplasias do Mediastino/diagnóstico , Neoplasias das Paratireoides/diagnóstico , Idoso de 80 Anos ou mais , Obstrução das Vias Respiratórias/diagnóstico , Obstrução das Vias Respiratórias/patologia , Obstrução das Vias Respiratórias/cirurgia , Biópsia por Agulha Fina , Diagnóstico Diferencial , Feminino , Humanos , Hiperparatireoidismo Primário/patologia , Hiperparatireoidismo Primário/cirurgia , Imageamento por Ressonância Magnética , Cisto Mediastínico/patologia , Cisto Mediastínico/cirurgia , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/cirurgia , Futilidade Médica , Invasividade Neoplásica , Glândulas Paratireoides/patologia , Neoplasias das Paratireoides/patologia , Neoplasias das Paratireoides/cirurgia , Tomografia Computadorizada por Raios X , Doenças da Traqueia/diagnóstico , Doenças da Traqueia/patologia , Doenças da Traqueia/cirurgiaRESUMO
The Hedgehog (Hh) family of intercellular signalling proteins have come to be recognised as key mediators in many fundamental processes in embryonic development. Their activities are central to the growth, patterning and morphogenesis of many different regions within the bodies of vertebrates. In some contexts, Hh signals act as morphogens in the dose-dependent induction of distinct cell fates within a target field, in others as mitogens in the regulation of cell proliferation or as inducing factors controlling the form of a developing organ. These diverse functions of Hh proteins raise many intriguing questions about their mode of action. Various studies have now demonstrated the function of Hh signalling in the control of cell proliferation, especially for stem cells and stem-like progenitors. Abnormal activation of the Hh pathway has been demonstrated in a variety of human tumours. Hh pathway activity in these tumours is required for cancer cell proliferation and tumour growth. Recent studies have uncovered the role for Hh signalling in advanced prostate cancer and demonstrated that autocrine signalling by tumour cells is required for proliferation, viability and invasive behaviour. Thus, Hh signalling represents a novel pathway in prostate cancer that offers opportunities for prognostic biomarker development, drug targeting and therapeutic response monitoring.
Assuntos
Proteínas Hedgehog/metabolismo , Neoplasias da Próstata/metabolismo , Transdução de Sinais , Animais , Células Epiteliais/metabolismo , Proteínas Hedgehog/genética , Humanos , Masculino , Mesoderma/metabolismo , Modelos Biológicos , Próstata/metabolismoRESUMO
Choroid plexus carcinomas are rare tumours, found chiefly during childhood. The commonest pattern of progression is via the neural axis. We present the case of a patient with unusual metastatic dissemination, affecting lungs and bones two years after diagnosis, and the approach adopted towards him.
Assuntos
Carcinoma/terapia , Neoplasias do Plexo Corióideo/terapia , Adulto , Neoplasias Ósseas/secundário , Carcinoma/secundário , Neoplasias do Plexo Corióideo/patologia , Humanos , Neoplasias Pulmonares/secundário , MasculinoRESUMO
The association of mediastinal germ-cell tumours (MGCTs) with haematologic neoplasms is a rare though well known circumstance, and few cases are found in the literature. Most of these refer to non-seminomatous tumours in young males. The diagnosis of the haematological condition is usually either synchronic or metachronic with that of the germ-cell tumour. From those cases that have been published, we know that the prognosis is poor and basically determined by the haematologic neoplasia. The case report we present is that of a young male with an initial diagnosis of both conditions. It was possible to apply specific treatment, initially in the case of the leukaemia, and later in the case of the germ-cell tumour. The approach adopted is a multidisciplinary one.
Assuntos
Leucemia Megacarioblástica Aguda , Neoplasias do Mediastino , Neoplasias Embrionárias de Células Germinativas , Neoplasias Primárias Múltiplas , Adulto , Humanos , Leucemia Megacarioblástica Aguda/diagnóstico , Leucemia Megacarioblástica Aguda/terapia , Masculino , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/terapia , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/terapiaRESUMO
Stem cells, as classically defined, are cells with a capacity to self-renew and to generate daughter cells that can differentiate down several cell lineages to form all of the cell types that are found in the mature tissue. Stem cells and tumour cells have many similar features, including infinite lifespan, self-renewal, multidrug resistance, telomerase expression and, in the instance of the prostate, androgen independence. Evidence supports a role for stem cells in the etiology of many types of cancer. The evolution of androgen-independent prostate carcinoma may reflect the emergence of stemlike prostate tumour cells. Because cancer may be a disease of stem cell lineages and Shh-Gli signalling controls the behaviour of precursors and of cells with stem cell properties in the mammalian tissues, prostate cancer might derive from inappropriate expansion of prostatic epithelial stem cell lineages caused by abnormal Shh-Gli function. This review attempts to integrate these recent results.