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1.
Clin Ter ; 174(2): 203-210, 2023.
Article in English | MEDLINE | ID: mdl-36920140

ABSTRACT

Abstract: Pancreatic cancer is associated to a high risk of malnutrition and neoplastic cachexia even at first diagnosis. Malnutrition is a negative prognostic factor for the outcome of surgery or medical oncology treatments. Despite the good awareness of the problem and the knowledge of the guidelines, the early recognition of malnutrition and its management are still uneven, mainly due to the lack of implementation of standardized and shared protocols and the shortage of dedicated clinical nutritionists and dieticians. An early and appropriate nutritional intervention is mandatory to improve the outcome of patients with pancreatic cancer at any stage of disease. The Mini Nutritional Assessment is useful tool to screen patients malnourished or at risk of malnutrition. The need for the establishment and implementation of an integrated hospital - territorial assistance as well as a home-delivered nutrition service is discussed.


Subject(s)
Malnutrition , Pancreatic Neoplasms , Humans , Malnutrition/diagnosis , Malnutrition/etiology , Malnutrition/therapy , Cachexia/diagnosis , Cachexia/etiology , Cachexia/therapy , Nutrition Assessment , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/therapy , Hospitals , Pancreatic Neoplasms
2.
Curr Neurol Neurosci Rep ; 22(8): 427-440, 2022 08.
Article in English | MEDLINE | ID: mdl-35674870

ABSTRACT

PURPOSE OF REVIEW: Neuroinflammation plays a significant role in Parkinson's disease (PD) etiology along with mitochondrial dysfunction and impaired proteostasis. In this context, mechanisms related to immune response can act as modifiers at different steps of the neurodegenerative process and justify the growing interest in anti-inflammatory agents as potential disease-modifying treatments in PD. The discovery of inherited gene mutations in PD has allowed researchers to develop cellular and animal models to study the mechanisms of the underlying biology, but the original cause of neuroinflammation in PD is still debated to date. RECENT FINDINGS: Cell autonomous alterations in neuronal cells, including mitochondrial damage and protein aggregation, could play a role, but recent findings also highlighted the importance of intercellular communication at both local and systemic level. This has given rise to debate about the role of non-neuronal cells in PD and reignited intense research into the gut-brain axis and other non-neuronal interactions in the development of the disease. Whatever the original trigger of neuroinflammation in PD, what appears quite clear is that the aberrant activation of glial cells and other components of the immune system creates a vicious circle in which neurodegeneration and neuroinflammation nourish each other. In this review, we will provide an up-to-date summary of the main cellular alterations underlying neuroinflammation in PD, including those induced by environmental factors (e.g. the gut microbiome) and those related to the genetic background of affected patients. Starting from the lesson provided by familial forms of PD, we will discuss pathophysiological mechanisms linked to inflammation that could also play a role in idiopathic forms. Finally, we will comment on the potential clinical translatability of immunobiomarkers identified in PD patient cohorts and provide an update on current therapeutic strategies aimed at overcoming or preventing inflammation in PD.


Subject(s)
Gastrointestinal Microbiome , Parkinson Disease , Animals , Humans , Inflammation/metabolism , Neuroinflammatory Diseases , Neurons/metabolism , Parkinson Disease/metabolism
3.
J Interv Card Electrophysiol ; 55(3): 267-275, 2019 Sep.
Article in English | MEDLINE | ID: mdl-30607667

ABSTRACT

BACKGROUND: Pulmonary vein isolation by cryoablation (PVI-C) is a standard therapy for the treatment of atrial fibrillation (AF); however, PVI-C can become a challenging procedure due to the anatomy of the left atrium and pulmonary veins (PVs). Importantly, the utility of imaging before the procedure is still unknown regarding the long-term clinical outcomes following PVI-C. The aim of the analysis is to evaluate the impact of imaging before PVI-C on procedural data and AF recurrence. METHODS: Patients with paroxysmal AF underwent an index PVI-C. Data were collected prospectively in the framework of 1STOP ClinicalService® project. Patients were divided into two groups according to the utilization of pre-procedural imaging of PV anatomy (via CT or MRI) or the non-usage of pre-procedural imaging. RESULTS: Out of 912 patients, 461 (50.5%) were evaluated with CT or MRI before the PVI-C and denoted as the imaging group. Accordingly, 451 (49.5%) patients had no pre-procedural imaging and were categorized as the no imaging group. Patient baseline characteristics were comparable between the two cohorts, but the ablation centers that comprised the imaging group had fewer PVI-C cases per year than the no imaging group (p < 0.001). The procedure, fluoroscopy, and left atrial dwell times were significantly shorter in the no imaging cohort (p < 0.001). The rates of complications were significantly greater in the imaging group compared to the no imaging group (6.9% vs. 2.7%; p = 0.003); this difference was attributed to differences in transient diaphragmatic paralysis. The 12-month freedom from AF was 76.2% in the imaging group and 80.0% in the no imaging group (p = 0.390). CONCLUSIONS: In our analysis, PVI-C was effective regardless of the availability of imaging data on PV anatomy.


Subject(s)
Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/surgery , Cryosurgery/methods , Pulmonary Veins/diagnostic imaging , Pulmonary Veins/surgery , Female , Humans , Italy , Magnetic Resonance Imaging , Male , Middle Aged , Prospective Studies , Tomography, X-Ray Computed
4.
Curr Mol Med ; 17(6): 405-420, 2017.
Article in English | MEDLINE | ID: mdl-29256350

ABSTRACT

Prostate cancer is one of the most difficult cancers to treat especially when it becomes hormone resistant such as castrate resistant prostate cancer (CRPC) and subsequent metastatic CRPC. Apart from the genetic alterations in prostate cancer, epigenetic modifications also play an important role in the development and neoplastic progression of this disease. These include DNA methylation, histone modifications, and non-coding microRNAs. miRNAs are a novel class of small endogenous single-stranded non-coding RNAs of 19-25 nucleotides in length that typically silence gene expression. Considering the reversibility of epigenetic alterations in early carcinogenesis process, reversion (correction) of these modifications by green tea catechins could be a promising strategy for cancer chemoprevention and therapy. Recent evidence suggests that green tea catechins such as epigallocatechin gallate (EGCG) not only act as epigenetic modulators but can also modify miRNA expression and their target mRNAs, consistently contributing to the inhibition of prostate carcinogenesis. Various studies also indicate that several green tea polyphenols (GTPs) exert synergistic effects with other cancer chemotherapeutic agents. Therefore, the use of appropriate combinations of green tea catechins with the existing chemotherapeutics will lead to a reduction in side effects without decreasing the chemotherapeutic effects. This review will summarize the key results from recent studies detailing the effects of green tea catechins such as EGCG on epigenetic alterations and miRNA expression in prostate cancer.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Catechin/pharmacology , Drug Synergism , Epigenesis, Genetic/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Prostatic Neoplasms/prevention & control , Tea/chemistry , Animals , Humans , Male , Prostatic Neoplasms/genetics
6.
Leukemia ; 31(11): 2407-2415, 2017 11.
Article in English | MEDLINE | ID: mdl-28321119

ABSTRACT

In chronic lymphocytic leukemia (CLL), the mechanisms controlling cell growth and proliferation in the presence of NOTCH1 mutations remain largely unexplored. By performing a gene expression profile of NOTCH1-mutated (NOTCH1-mut) versus NOTCH1 wild-type CLL, we identified a gene signature of NOTCH1-mut CLL characterized by the upregulation of genes related to ribosome biogenesis, such as nucleophosmin 1 (NPM1) and ribosomal proteins (RNPs). Activation of NOTCH1 signaling by ethylenediaminetetraacetic acid or by coculture with JAGGED1-expressing stromal cells increased NPM1 expression, and inhibition of NOTCH1 signaling by either NOTCH1-specific small interfering RNA (siRNA) or γ-secretase inhibitor reduced NPM1 expression. Bioinformatic analyses and in vitro activation/inhibition of NOTCH1 signaling suggested a role of MYC as a mediator of NOTCH1 effects over NPM1 and RNP expression in NOTCH1-mut CLL. Chromatin immunoprecipitation experiments performed on NOTCH1 intracellular domain (NICD)-transfected CLL-like cells showed the direct binding of NOTCH1 to the MYC promoter, and transfection with MYC-specific siRNA reduced NPM1 expression. In turn, NPM1 determined a proliferation advantage of CLL-like cells, as demonstrated by NPM1-specific siRNA transfection. In conclusion, NOTCH1 mutations in CLL are associated with the overexpression of MYC and MYC-related genes involved in protein biosynthesis including NPM1, which are allegedly responsible for cell growth and/or proliferation advantages of NOTCH1-mut CLL.


Subject(s)
Genes, myc , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Mutation , Nuclear Proteins/metabolism , Receptor, Notch1/genetics , Ribosomes/metabolism , Cell Proliferation , Coculture Techniques , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Nucleophosmin , Receptor, Notch1/metabolism , Signal Transduction , Tumor Cells, Cultured , Up-Regulation
7.
Histol Histopathol ; 32(4): 371-377, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27411919

ABSTRACT

BACKGROUND: P53, a crucial suppressor of tumor formation, generates multiple isoforms, whose role in disease is still being defined. METHODS: By immunohistochemistry, we studied the expression of P53 protein and relative isoforms in benign papillomas (PA, n=9), inverted papilloma (IPA, n=10) and squamous cell carcinomas (SCC, n=21). RESULTS: In all lesions, P53 isoforms were significantly more expressed than P53. Immunoexpression of P53 matched with P53 isoforms in IPA as well as in SCC. Simultaneous immunoexpression of P53 and related isoforms was double in SCC compared to IPA (10% vs 24%), while expression of P53 isoforms was strongly reduced (70% vs 43%). IPA showed the highest percentage of both reactive cases and immunostained cells expressing P53 isoforms. CONCLUSIONS: We found the higher expression of P53 isoforms in IPA and SCC compared to PA, suggesting their role in local aggressiveness and malignant proliferation in head-neck lesions.


Subject(s)
Carcinoma, Squamous Cell/pathology , Head and Neck Neoplasms/pathology , Papilloma, Inverted/pathology , Papilloma/pathology , Tumor Suppressor Protein p53/biosynthesis , Adult , Aged , Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/metabolism , Female , Head and Neck Neoplasms/metabolism , Humans , Immunohistochemistry , Male , Middle Aged , Papilloma/metabolism , Papilloma, Inverted/metabolism , Protein Isoforms/antagonists & inhibitors , Protein Isoforms/biosynthesis , Protein Isoforms/genetics , Squamous Cell Carcinoma of Head and Neck , Tumor Suppressor Protein p53/antagonists & inhibitors , Tumor Suppressor Protein p53/genetics
8.
Leukemia ; 30(1): 182-9, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26165233

ABSTRACT

In chronic lymphocytic leukemia (CLL), NOTCH1 mutations have been associated with clinical resistance to the anti-CD20 rituximab, although the mechanisms behind this peculiar behavior remain to be clarified. In a wide CLL series (n=692), we demonstrated that CLL cells from NOTCH1-mutated cases (87/692) were characterized by lower CD20 expression and lower relative lysis induced by anti-CD20 exposure in vitro. Consistently, CD20 expression by CLL cells was upregulated in vitro by γ-secretase inhibitors or NOTCH1-specific small interfering RNA and the stable transfection of a mutated (c.7541-7542delCT) NOTCH1 intracellular domain (NICD-mut) into CLL-like cells resulted in a strong downregulation of both CD20 protein and transcript. By using these NICD-mut transfectants, we investigated protein interactions of RBPJ, a transcription factor acting either as activator or repressor of NOTCH1 pathway when respectively bound to NICD or histone deacetylases (HDACs). Compared with controls, NICD-mut transfectants had RBPJ preferentially complexed to NICD and showed higher levels of HDACs interacting with the promoter of the CD20 gene. Finally, treatment with the HDAC inhibitor valproic acid upregulated CD20 in both NICD-mut transfectants and primary CLL cells. In conclusion, NOTCH1 mutations are associated with low CD20 levels in CLL and are responsible for a dysregulation of HDAC-mediated epigenetic repression of CD20 expression.


Subject(s)
Antigens, CD20/analysis , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Mutation , Receptor, Notch1/genetics , Histone Deacetylase 1/analysis , Histone Deacetylase 2/analysis , Histone Deacetylase Inhibitors/pharmacology , Humans , Immunoglobulin J Recombination Signal Sequence-Binding Protein/metabolism , Leukemia, Lymphocytic, Chronic, B-Cell/immunology
9.
Curr Oncol ; 22(2): 113-21, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25908910

ABSTRACT

BACKGROUND: Enrolling patients in studies of pancreatic ductal adenocarcinoma (pdac) is challenging because of the high fatality of the disease. We hypothesized that a prospective clinic-based study with rapid ascertainment would result in high participation rates. Using that strategy, we established the Quebec Pancreas Cancer Study (qpcs) to investigate the genetics and causes of pdac and other periampullary tumours (pats) that are also rare and underrepresented in research studies. METHODS: Patients diagnosed with pdac or pat were introduced to the study at their initial clinical encounter, with a strategy to enrol participants within 2 weeks of diagnosis. Patient self-referrals and referrals of unaffected individuals with an increased risk of pdac were also accepted. Family histories, epidemiologic and clinical data, and biospecimens were collected. Additional relatives were enrolled in families at increased genetic risk. RESULTS: The first 346 completed referrals led to 306 probands being enrolled, including 190 probands affected with pdac, who represent the population focus of the qpcs. Participation rates were 88.4% for all referrals and 89.2% for pdac referrals. Family history, epidemiologic and clinical data, and biospecimens were ascertained from 91.9%, 54.6%, and 97.5% respectively of patients with pdac. Although demographics and trends in risk factors in our patients were consistent with published statistics for patients with pdac, the qpcs is enriched for families with French-Canadian ancestry (37.4%), a population with recurrent germ-line mutations in hereditary diseases. CONCLUSIONS: Using rapid ascertainment, a pdac and pat research registry with high participation rates can be established. The qpcs is a valuable research resource and its enrichment with patients of French-Canadian ancestry provides a unique opportunity for studies of heredity in these diseases.

10.
Eur Rev Med Pharmacol Sci ; 18(2 Suppl): 40-6, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25535191

ABSTRACT

BACKGROUND: Several trials showed that early laparoscopic cholecystectomy is superior to delayed laparoscopic cholecystectomy for the treatment of acute cholecystitis. However actual practice does not conform to current evidence. The aim of this study is to compare outcomes and total hospital costs between early and delayed laparoscopic cholecystectomy for acute cholecystitis. PATIENTS AND METHODS: A retrospective analysis of patients with acute cholecystitis that underwent a laparoscopic cholecystectomy at our institutions was performed. Patients were divided into 2 groups on the basis of the treatment received and statistical analysis was performed. RESULTS: The study included 91 patients, 52 female and 39 male, with a mean age of 55. Early surgery was performed in 32 cases and delayed surgery in 59 cases. The two groups were comparable for demographics data and severity of disease on admission. There was a no significant difference (p = 0.174) in the mean operative time between early (54.8 min) and delayed group (47.8 min). Conversion rate was higher in the early group (34.3% vs. 20.3%), but difference was not statistically significant (p = 0.223). The overall complications rate was comparable (18.7% early vs. 16.9% delayed, p = 0.941). Length of postoperative stay (4.3 vs. 3.8 days) was similar (p = 0.437), but total hospital stay was significantly 4 days shorter in the early group (p < 0.0001). The mean total cost was higher for the delayed group (4171 vs. 6041), with a significant difference of 1870 Euro (p < 0.0001). CONCLUSIONS: Early laparoscopic cholecystectomy has an outcome comparable to the delayed procedure, with a shorter total hospital stay and lower total costs, and it should be considered as the preferred approach in treatment of acute cholecystitis.


Subject(s)
Cholecystectomy, Laparoscopic/economics , Cholecystectomy, Laparoscopic/methods , Cholecystitis, Acute/economics , Cholecystitis, Acute/surgery , Adult , Aged , Aged, 80 and over , Female , Hospital Costs , Humans , Italy , Length of Stay , Male , Middle Aged , Retrospective Studies , Time Factors
11.
Eur Rev Med Pharmacol Sci ; 18(2 Suppl): 60-8, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25535194

ABSTRACT

BACKGROUND: Laparoscopic cholecystectomy has become the standard treatment for symptomatic gallstones. However, a conversion to open surgery is sometimes still required to complete the procedure safely. The aim of this study is to identify the predictive factors of conversion from laparoscopic to open cholecystectomy in both elective and emergency cases. PATIENTS AND METHODS: A retrospective review of all patients underwent laparoscopic cholecystectomy for symptomatic gallstones from January 2011 to October 2013 was performed. Data considered for analysis were: demographic data, comorbidities, preoperative laboratory values, preoperative ERCP, indication for surgery, and the timing of the intervention in acute cholecystitis. Conversion to open cholecystectomy was chosen as the dependent variable for both, univariate and multivariate analysis. RESULTS: 414 patients underwent laparoscopic cholecystectomy. 245 were female (59.1%) and 169 (40.8%) male, with a mean age of 51.7±16.4 years. The indication for surgery was acute cholecystitis in 91 cases (21.9%). Lithiasis of the bile duct was found in 40 patients (9.6%), and it was identified preoperatively in 37 patients, all treated with a preoperative ERCP. Conversion to open occurred in 33 cases (7.9%). Univariate analysis revealed as risk factor for conversion: increased age, acute cholecystitis, comorbidities, elevated white blood cell count, increased level of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transpeptidase, C-reactive protein, and fibrinogen. Multivariate logistic regression analysis showed that acute cholecystitis (OR 5.63) and age > 65 years (OR 3.025) were independent predictive factors for conversion. CONCLUSIONS: These patients should be properly informed of their increased risk of conversion and should be operated by surgeons skilled in laparoscopic procedures to reduce this risk.


Subject(s)
Cholecystectomy, Laparoscopic/methods , Cholecystectomy/methods , Gallstones/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Cholecystectomy/adverse effects , Cholecystectomy, Laparoscopic/adverse effects , Elective Surgical Procedures/methods , Female , Gallstones/pathology , Humans , Male , Middle Aged , Multivariate Analysis , Retrospective Studies , Risk Factors , Young Adult
12.
Transl Med UniSa ; 8: 75-9, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24779000

ABSTRACT

Monoclonal B-cell lymphocytosis (MBL) is an asymptomatic hematologic condition defined by the presence of a small (<5 x 10(9)/L) clonal B-cell population in the peripheral blood in the absence of lymph-node enlargement, cytopenias or autoimmune diseases. It is found in approximately 3-12% of normal persons depending on the accuracy of analytical techniques applied. According to the immunophenotypic profile of clonal B-cells, the majority of MBL cases (75%) are classified as chronic lymphocytic leukemia (CLL)-like. This form may progress into CLL at a rate of 1-2% per year. It is thought that CLL is always preceded by MBL. The remaining MBL cases are defined as atypical CLL-like (CD5+/CD20(bright)) and CD5(-) MBL. The MBL clone size is quite heterogenous. Accordingly, two forms of MBL are identified: i) high-count, or 'clinical' MBL, in which an evidence of lymphocytosis (<5 x 10(9)/L clonal B-cells) is seen, and ii) a low-count MBL, in which a normal leukocyte count is found and that is identified only in population-screening studies. Both forms of MBL may carry the cytogenetic abnormalities that are the hallmark of CLL, including 13q-, 17p- and trisomy 12. Consistent with the indolent phenotype of this condition, genetic lesions, such as TP53, ATM, NOTCH1 and SF3B1 mutations, usually associated with high-risk CLL, are rarely seen. Overall, no prognostic indicator of evolution of MBL to overt CLL has been found at present time. However, taking into account this possibility, a clinical and lab monitoring (at least annually), is recommended.

14.
Leukemia ; 28(5): 1060-70, 2014 May.
Article in English | MEDLINE | ID: mdl-24170027

ABSTRACT

The purpose of this study was to compare the expression and function of NOTCH1 in chronic lymphocytic leukemia (CLL) patients harboring a wild-type (WT) or mutated NOTCH1 gene. NOTCH1 mRNA and surface protein expression levels were independent of the NOTCH1 gene mutational status, consistent with the requirement for NOTCH1 signaling in this leukemia. However, compared with NOTCH1-WT CLL, mutated cases displayed biochemical and transcriptional evidence of an intense activation of the NOTCH1 pathway. In vivo, expression and activation of NOTCH1 was highest in CLL cells from the lymph nodes as confirmed by immunohistochemistry. In vitro, the NOTCH1 pathway was rapidly downregulated, suggesting that signaling relies upon micro-environmental interactions even in NOTCH1-mutated cases. Accordingly, co-culture of Jagged1(+) (the NOTCH1 ligand) nurse-like cells with autologous CLL cells sustained NOTCH1 activity over time and mediated CLL survival and resistance against pro-apoptotic stimuli, both abrogated when NOTCH1 signaling was pharmacologically switched off. Together, these results show that NOTCH1 mutations have stabilizing effects on the NOTCH1 pathway in CLL. Furthermore, micro-environmental interactions appear critical in activating the NOTCH1 pathway both in WT and mutated patients. Finally, NOTCH1 signals may create conditions that favor drug resistance, thus making NOTCH1 a potential molecular target in CLL.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Mutation , Receptor, Notch1/genetics , Down-Regulation , Flow Cytometry , Humans , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Signal Transduction
15.
Cell Death Differ ; 20(7): 920-30, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23519076

ABSTRACT

Mutations in the PINK1 gene are a frequent cause of autosomal recessive Parkinson's disease (PD). PINK1 encodes a mitochondrial kinase with neuroprotective activity, implicated in maintaining mitochondrial homeostasis and function. In concurrence with Parkin, PINK1 regulates mitochondrial trafficking and degradation of damaged mitochondria through mitophagy. Moreover, PINK1 can activate autophagy by interacting with the pro-autophagic protein Beclin-1. Here, we report that, upon mitochondrial depolarization, PINK1 interacts with and phosphorylates Bcl-xL, an anti-apoptotic protein also known to inhibit autophagy through its binding to Beclin-1. PINK1-Bcl-xL interaction does not interfere either with Beclin-1 release from Bcl-xL or the mitophagy pathway; rather it protects against cell death by hindering the pro-apoptotic cleavage of Bcl-xL. Our data provide a functional link between PINK1, Bcl-xL and apoptosis, suggesting a novel mechanism through which PINK1 regulates cell survival. This pathway could be relevant for the pathogenesis of PD as well as other diseases including cancer.


Subject(s)
Apoptosis/physiology , Mitochondria/physiology , Protein Kinases/physiology , bcl-X Protein/metabolism , Apoptosis Regulatory Proteins/physiology , Autophagy/physiology , Beclin-1 , Cell Line, Tumor , Cell Survival/physiology , HEK293 Cells , Humans , Membrane Proteins/physiology , Phosphorylation/physiology , Signal Transduction/physiology
16.
Int J Immunopathol Pharmacol ; 26(1): 117-25, 2013.
Article in English | MEDLINE | ID: mdl-23527714

ABSTRACT

Regulatory T cells (Tregs) are considered to be key immunomodulatory cells of the immune system and are increased in chronic lymphocytic leukemia (CLL). Rai stage 0 identifies patients with early stage CLL for which there is no effective intervention at the present time and a "wait and see" policy is usually adopted. Some biological and clinical studies have reported that green tea constituents, such as epigallocatechin-gallate (EGCG), have antitumor effects on hematologic malignancies including CLL. We report data on a clinical trial in which green tea extracts were given orally to 12 patients with stage 0 CLL and 12 healthy subjects. Ten patients and 10 controls completed the 6-month scheduled therapy. Two patients and 2 controls stopped therapy within 1 month because of tachycardia and epigastralgia. Eight out 10 evaluable patients (80 percent) showed a reduction of lymphocytosis and absolute number of circulating Tregs, as well. One patient (10 percent) had a stabilization of lymphocytosis and a reduction of Tregs, and 1 patient (10 percent) showed an increase of both lymphocytosis and Tregs. Only the non-responding patient progressed after 5 months from the end of green tea administration and chemotherapy was given. Interestingly, both IL-10 and TGF-beta serum levels declined throughout the green tea intake period, in both patients and controls. These data seem to indicate that green tea is able to modulate circulating Tregs in CLL patients with early stage of the disease. This can result in the control of lymphocytosis as well as in the prevention of disease progression.


Subject(s)
Camellia sinensis , Immunologic Factors/pharmacology , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Plant Extracts/pharmacology , T-Lymphocytes, Regulatory/drug effects , Adult , Aged , Aged, 80 and over , CD4 Lymphocyte Count , Caffeine/analysis , Catechin/analogs & derivatives , Catechin/analysis , Female , Humans , Immunologic Factors/chemistry , Interleukin-10/blood , Male , Middle Aged , Plant Extracts/chemistry , T-Lymphocytes, Regulatory/immunology , Transforming Growth Factor beta/blood
17.
Med. cután. ibero-lat.-am ; 40(6): 184-190, nov.-dic. 2012. ilus
Article in Spanish | IBECS | ID: ibc-108097

ABSTRACT

La Hidradenitis Supurativa o Enfermedad de Verneuil es un proceso inflamatorio crónico, recurrente que afecta las glándulas apócrinas de axila, ingle, periné, cuero cabelludo y región anoperineal. Se desconoce la etiología precisa. Es una enfermedad poco frecuente, mal diagnosticada, se estima la incidencia en 1 cada 300 adultos. Afecta más a mujeres y personas de raza negra, sin embargo la enfermedad de localización perianal afecta más a varones. El tratamiento médico mitigaría los síntomas pero la mayoría de los pacientes presentan lesiones crónicas que requerirán tratamiento quirúrgico. El Carcinoma de Células Escamosas es una complicación rara vez informada que se desarrolla en las lesiones crónicas de Hidradenitis Supurativa de larga evolución. Presentamos un caso de un paciente de sexo masculino, de 51 años de edad, que presenta sobre antiguas lesiones cicatrizales formación tumoral multilobulada, ulcerada centralmente localizada en región glútea-perineal izquierda de 3 meses de evolución. Se realizaron métodos complementarios arribando al diagnóstico de Hidradenitis Supurativa con Transformación Carcinomatosa (Carcinoma de Células Escamosas). Se realizó tratamiento quirúrgico con posterior injerto cutáneo con excelente evolución. Motiva ésta presentación la localización infrecuente y la complicación inusual. Como dato relevante cabe destacar las escasas publicaciones sobre dicho tema (AU)


Hidradenitis Suppurativa or Verneuil's disease is a chronic inflammatory recurring process that affects the apocrine glands of the armpit, groin, perineal area, scalp and an operineal area. Its accurate ethiology is unknown. It is a rare disease, it is misdiagnosed and its incidence rate is estimated in 1 every 300 adults. It affects mainly women and black race people. However the perianal localization disease affects mainly men. The medical treatment would mitigate the symptoms but most patients have chronic lesions that would require surgical treatment. The squamous cell carcinoma is a rarely reported complication which develops in the chronic lesions of Hidradenitis Suppurativa of long-term evolution. We present a case of a male patient, 51 years old, who has, on old scar lesions, a centrally ulcerated multilobulated tumor formation of 3 months of evolution localized in the left gluteo-perineal area. Complementary methods were used which led to the diagnostics of Hydradernitis Suppurativa with Carcinomatose Transformation (Squamous cellcarcinoma). Surgical treatment followed by skin graft was used with excellent evolution. The reason for this presentation is the infrequent localization and the unusual complication. Something important to point out is that publications on this topic are rare (AU)


Subject(s)
Humans , Male , Middle Aged , Hidradenitis Suppurativa/pathology , Carcinoma, Squamous Cell/pathology , Skin Neoplasms/pathology , Risk Factors , Skin Transplantation
18.
Exp Oncol ; 34(3): 306-11, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23070016

ABSTRACT

The recognition and removal of apoptotic cells by tissue macrophages and nonprofessional phagocytes, in a process called efferocytosis, is critical for development, tissue homeostasis and resolution of inflammation. Apoptotic bodies arising in tumor tissue are ingested by viable neoplastic cells and by resident macrophages. We described tumor cell phagocytosis of apoptotic neutrophils in human gastric carcinomas. This phenomenon is analogous to neutrophil efferocytosis performed by macrophages and by nonprofessional phagocytes during inflammatory reaction but is distinct by other types of cell-in-cell phenomena including emperipolesis and entosis both cytologically and biologically. In this review, we discussed them in their ultrastructural morphology, physiological roles, and clinicopathologic implications. This article is part of a Special Issue entitled "Apoptosis: Four Decades Later".


Subject(s)
Apoptosis , Neutrophils , Phagocytosis , Stomach Neoplasms , Apoptosis/immunology , Apoptosis/physiology , Cytophagocytosis/immunology , Cytophagocytosis/physiology , Emperipolesis/immunology , Emperipolesis/physiology , Entosis/immunology , Entosis/physiology , Humans , Inflammation/immunology , Inflammation/metabolism , Macrophages , Neutrophils/classification , Neutrophils/immunology , Neutrophils/physiology , Phagocytes/pathology , Phagocytes/physiology , Phagocytosis/immunology , Phagocytosis/physiology , Stomach Neoplasms/immunology , Stomach Neoplasms/pathology
19.
Med. cután. ibero-lat.-am ; 40(5): 154-157, sept.-oct. 2012. ilus
Article in Spanish | IBECS | ID: ibc-108090

ABSTRACT

La leishmaniasis es la infección producida por protozoos del género Leishmania. Presenta diferentes formas clínicas, dentro de las cuales, la leishmaniasis mucocutánea es una de las que conlleva mayor gravedad debido al compromiso de la vía aérea superior, que puede producir secuelas incapacitantes e incluso la muerte. Presentamos el caso de un paciente con diagnóstico de leishmaniasis mucocutánea con importante compromiso laríngeo, el cual tuvo excelente respuesta al tratamiento con antimoniales pentavalentes (AU)


Leishmaniasis is an infection caused by protozoa of the genus Leishmania. Mucocutaneous leishmaniasis is one of the clinical forms that presents more severity, due to the involvement of the upper airway, which can lead to incapacitating consequences or even death. We report the case of a patient with diagnosis of mucocutaneous leishmaniasis with significant laryngeal involvement which had excellent response to treatment with pentavalent antimonials (AU)


Subject(s)
Humans , Male , Adult , Leishmaniasis, Mucocutaneous/microbiology , Laryngitis/microbiology , Antimony/therapeutic use , Leishmania/pathogenicity , Anti-Bacterial Agents/therapeutic use
20.
Ann Oncol ; 23(6): 1499-502, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22039089

ABSTRACT

BACKGROUND: The best therapeutic approach for primary plasma cell leukemia (PPCL) remains unknown so far. In very limited studies, the poor clinical outcome of this aggressive variant of multiple myeloma seemed to be ameliorated by the use of the proteasome inhibitor bortezomib. Aiming to provide more consolidated data, this multicenter retrospective survey focused on unselected and previously untreated PPCL patients who had received bortezomib as frontline therapy. PATIENTS AND METHODS: Twenty-nine patients with PPCL were collected. Bortezomib was given at standard doses and schedules, in various combinations with dexamethasone, thalidomide, doxorubicin, melphalan, prednisone, vincristine, and cyclophosphamide. RESULTS: An overall response rate of 79% was observed, with 38% of at least very good partial remission. Grade 3-4 hematological, neurological, infectious, and renal toxic effects occurred in 20%, 21%, 16%, and 4% of patients, respectively. After a median follow-up of 24 months, 16 patients were alive (55%), 12 of whom were in remission phase and 4 relapsed. The best long-term results were achieved in patients who received stem-cell transplantation after bortezomib induction. CONCLUSION: Bortezomib, used as initial therapy, is able to increase the percentage and the quality of responses in PPCL patients, producing a significant improvement of survival.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Plasma Cell/drug therapy , Adult , Aged , Aged, 80 and over , Boronic Acids/administration & dosage , Bortezomib , Cyclophosphamide/administration & dosage , Dexamethasone/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Female , Humans , Kaplan-Meier Estimate , Leukemia, Plasma Cell/mortality , Male , Melphalan/administration & dosage , Middle Aged , Prednisone/administration & dosage , Pyrazines/administration & dosage , Retrospective Studies , Thalidomide/administration & dosage , Treatment Outcome , Vincristine/administration & dosage
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