0000000000993485
AUTHOR
Giuseppe Cicero
MicroRNAs in Colorectal Cancer Drug Resistance: Shooters become Targets
Copyright: © 2013 Fanale D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. MicroRNAs (MiRNAs) are involved in the regulation of several biological processes such as development, differentiation, metabolism, apoptosis and proliferation. Recently, it has been shown that deregulated expression of miRNAs are present in different human cancers, suggesting a potential role in carcinogenesis [1,2]. Recent evidence suggests that miRNAs may represent potential new therapeutic approaches in patients with dru…
Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer Patients Progressing after Docetaxel: A Prospective Single-Center Study
<b><i>Purpose:</i></b> The present study aims to evaluate the efficacy of cabazitaxel in combination with prednisone treatment in Italian patients affected by hormone-refractory metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel plus prednisone. <b><i>Methods:</i></b> Thirty patients with mCRPC were enrolled between June 2013 and January 2016 (the last follow-up was in January 2016). Cabazitaxel was used according to the summary of product characteristics and administered at a dose of 25 mg/m<sup>2</sup> every 3 weeks plus oral prednisone at a dose of 5-mg tablets twice a day continuously. The…
Leptin plasma levels in patients undergoing prostate biopsy. a preliminary study in 50 patients
Introduction/Aim: To reduce the number of negative prostate biopsies and to detect clinical significant prostate tumors in patients with elevated serum PSA represent major challenges in urological oncology. Prostate tumors diagnosed in patients with elevated Body Mass Index (BMI) show higher Gleason score and more aggressive biological behavior than those diagnosed in normal population (1). Elevated plasma levels of leptin and other adipose tissue derived factors (adipokines), are evident in obese men (2). Many studies have investigated the role of leptin as a putative molecular mediator between obesity and prostate cancer with contradictory results. Also in normal or overweight (BMI <30) m…
Significance of P16INK4A hypermethylation gene in primary head/neck and colorectal tumors: it is a specific tissue event? Results of a 3-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study
Background Methylation of the p16 promoter is one of the most frequent mechanisms of gene inactivation; its incidence is extremely variable according to the type of tumor involved. Our purpose was to analyze the hypermethylation of the p16 promoter in laryngeal squamous cell carcinomas (LSCC), salivary gland (SG) tumors and in colorectal cancer (CRC), to detect any possible association with the clinicopathological features and to determine the prognostic significance of the p16 gene in the tumors analyzed. Patients and methods The hypermethylation of the p16 promoter was prospectively analyzed, by MSP, in a consecutive series of 64 locally advanced LSCC patients, in a consecutive series of …
Does Exist A Correlation Between BMI and Gleason Patterns 4 and 5 At Prostate Biopsy?
Background: Obesity has been related with higher Gleason grade and worse prognosis. Increasing proportion of Gleason pattern 4 or 5 is a critical factor for biochemical recurrence, progression and mortality. The endocrine activity of visceral fat could be responsible of the differentation of the prostatic malignant cell towards a more aggressive fenotype. The aim of our study was to correlate Body Mass Index with the presence of Gleason pattern 4 or higher at biopsy. Materials and Methods: Consecutive patients with positive prostate biopsy were included. A transrectal prostate biopsy procedure with 12 cores, was performed. All tissue samples were reviewed. Results: Out of 135 patients diagn…
Bortezomib: a new pro-apoptotic agent in cancer treatment.
Bortezomib is a proteasome inhibitor. It targets the ubiquitin-proteasome pathway with subsequent inhibition of the degradation of proteins involved in cell cycle regulation and cancer cell survival. The best known molecular mechanism concerns the inhibition of IkappaB breakdown and the related stabilization of NFkappaB, thus preventing its translocation to the nucleus for the activation of downstream pathways. Bortezomib is the only drug in this class which has been approved for clinical use. It has shown an efficient antitumor effect in a phase III clinical trial (APEX) involving relapsed multiple myeloma patients. Response rate, time to progression and overall survival have been improved…
HSP10,HSP70 AND HSP90 IMMUNOHISTOCHEMICAL LEVELS CHANGE IN ULCERATIVE COLITIS AFTER THERAPY
Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) characterized by damage of large bowel mucosa and frequent extra-intestinal autoimmune comorbidities. The role played in IBD pathogenesis by molecular chaperones known to interact with components of the immune system involved in inflammation is unclear. We previously demonstrated that mucosal Hsp60 decreases in UC patients treated with conventional therapies (mesalazine, probiotics), suggesting that this chaperonin could be a reliable biomarker useful for monitoring response to treatment, and that it might play a role in pathogenesis. In the present work we investigated three other heat shock protein/molecular chaperones:…
Are erlotinib and gefitinib interchangeable, opposite or complementary for non-small cell lung cancer treatment? Biological, pharmacological and clinical aspects
Abstract: Gefitinib and erlotinib are the two anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) approved for treatment of advanced NSCLC patients. These drugs target one of the most important pathways in lung carcinogenesis and are able to exploit the phenomenon of 'oncogene addiction', with different efficacy according to EGFR gene mutational status in tumor samples. Gefitinib has been approved only for EGFR mutation bearing patients regardless the line of treatment, while erlotinib is also indicated in patients without EGFR mutation who undergo second- or third-line treatment. Some studies evaluated the main differences between these drugs both for direct comp…
The Clinical Efficacy of Radium-223 for Bone Metastasis in Patients with Castration-Resistant Prostate Cancer: An Italian Clinical Experience.
<b><i>Background/Aim:</i></b> Prostate cancer frequently causes bone metastases and skeletal events that impair quality of life (QoL) and survival. The alpha emitter radium-223 is a new drug that improves treatment in men with castration-resistant prostate cancer (CRPC) and bone metastases. Our aim was to evaluate the effectiveness of radium-223. <b><i>Subjects and Methods:</i></b> In this retrospective study we enrolled 48 subjects. Pain reduction, alkaline phosphatase (ALP), time to first symptomatic skeletal event, and QoL were the variables we evaluated. <b><i>Results:</i></b> Radium-223 was well tolerated, with a m…
Co-expression of CD133+/CD44+in human colon cancer and liver metastasis
Although relatively good therapeutic results are achieved in non-advanced cancer, the prognosis of the advanced colon cancer still remains poor, dependent on local or distant recurrence of the disease. One of the factors responsible for recurrence is supposed to be cancer stem cells (CSCs) or tumor-initiating cells, which are a population of cancer cells with ability to perpetuate themselves through self-renewal and to generate differentiated cells, thought to be responsible for tumor recurrence. This study globally approach the possible role of tissue-derived stem cells in the initiation of colon cancer and its metastatic process in the liver. Fresh surgical specimens from colon cancer, no…
Terapia medica e supporto psicologico in un gruppo di pazienti affette da carcinoma mammario
Hypoxia and Human Genome Stability: Downregulation of BRCA2 Expression in Breast Cancer Cell Lines
Previously, it has been reported that hypoxia causes increased mutagenesis and alteration in DNA repair mechanisms. In 2005, an interesting study showed that hypoxia-induced decreases in BRCA1 expression and the consequent suppression of homologous recombination may lead to genetic instability. However, nothing is yet known about the involvement of BRCA2 in hypoxic conditions in breast cancer. Initially, a cell proliferation assay allowed us to hypothesize that hypoxia could negatively regulate the breast cancer cell growth in short term in vitro studies. Subsequently, we analyzed gene expression in breast cancer cell lines exposed to hypoxic condition by microarray analysis. Interestingly,…
Emergenze metaboliche
Reduced-dose of doublet chemotherapy combined with anti-EGFR antibodies in vulnerable older patients with metastatic colorectal cancer: Data from the REVOLT study
Abstract Objectives To assess the toxicity patterns and effectiveness of doublet chemotherapy when administered at reduced doses of 20% (FOLFOX or FOLFIRI) in combination with anti-EGFR antibodies (cetuximab or panitumumab) in old, vulnerable patients with metastatic colorectal cancer (mCRC). Patients and methods We performed a retrospective observational study of RAS and BRAF wild-type, vulnerable patients aged ≥70 years with previously untreated mCRC. The primary endpoint was safety, and secondary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results One hundred and eighteen patients were collected from 14 selected Italian centres.…
Efficacy and Safety of the Oral Multikinase Regorafenib in Metastatic Colorectal Cancer.
<b><i>Background/Aim:</i></b> A clinical trial demonstrated that treatment with oral multikinase regorafenib improved overall survival (OS), progression-free survival (PFS), and disease control [García-Alfonso et al.: J Clin Transl Oncol 2016;18:1072-1081; Bertocchi et al.: J Chemother 2017;29:102-105]. In this study, we aimed to evaluate its effectiveness in Italian patients with hormone-refractory metastatic castration-resistant prostate cancer (mCRPC) progressing after chemotherapy with docetaxel plus prednisone. <b><i>Materials and Methods:</i></b> 60 patients were enrolled. OS has been assessed as the primary endpoint while PFS, quality o…
Gemcitabine (GEM) plus oxaliplatin, folinic acid, and 5-fluorouracil (FOLFOX-4) in patients with advanced gastric cancer
Abstract BACKGROUND AND AIMS: oxaliplatin in combination with folinic acid (FA) and infusional 5-fluorouracil (5-FU) has shown significant anti-tumor activity in gastric cancer patients (FOLFOX). Previous studies have shown that gemcitabine (GEM), a new fluorinated anti-metabolite, enhances the individual anti-tumor activity of either 5-FU or oxaliplatin. We have therefore designed a multi-center phase II trial in order to test a novel GEM+FOLFOX-4 regimen in patients with metastatic gastric cancer. METHODS: we enrolled 36 patients, 28 males and 8 females, with an average age of 64.4 years (range 37-78), who received bi-weekly treatment with GEM (1,000 mg/m2 on day 1), levo-FA (100 mg/m2 on…
Pegylated liposomal doxorubicin (PLD) and weekly paclitaxel (P) as second line chemotherapy in metastatic bladder cancer.
Relationship between anxiety level and radiological investigation. Comparison among different diagnostic imaging exams in a prospective single-center study
Objective: Every patient could feel anxious when he waits in a radiological department to undergo diagnostic exams. The aim of our study is to evaluate the impact of the radiological exams on patient anxiety. Materials and methods: We evaluated 343 patients (mean age 54.83 years) who underwent different types of diagnostic exams in the Department of Diagnostic Imaging at our Hospital from April 2013 to August 2014. We administered to patients the State and Trait Anxiety Inventory Test, which detected with high sensitivity both state anxiety and trait anxiety. A team of clinical psychologists and radiologists evaluated the scores obtained. Results: 83 out of 343 patients were excluded becaus…
Cetuximab rechallenge in metastatic colorectal cancer patients: how to come away from acquired resistance?
Background: Scientific data provide the evidence that secondary K-RAS mutations do not occur during anti-epidermal growth factor receptor therapy in colorectal cancer patients. This multicenter phase II prospective study aims to investigate the activity of a retreatment with a cetuximab-based therapy. Patients and methods: We enrolled 39 irinotecan-refractory patients who had a clinical benefit after a line of cetuximab- plus irinotecan-based therapy and then a progression of disease for which underwent a new line chemotherapy and finally, after a clear new progression of disease, were retreated with the same cetuximab- plus irinotecan-based therapy. Results: Median number of therapeutic li…
Correlation between leptin plasmatic levels in non-obese patients and detection rate at prostate biopsy”- Poster P147
Immunotherapy for recurrent ovarian cancer: a further piece of the puzzle or a striking strategy?
Introduction: Treatment of ovarian cancer has been long standardized with the inclusion of surgery and chemotherapy based on platinum and taxanes, this strategy reaching high remission rates. However, when this treatment fails, further options are available with little benefit. Since ovarian cancer has specific immunologic features, actually immunotherapy is under evalua- 15 tion to overcome treatment failure in patients experiencing recurrence. Areas covered: Immunogenicity of ovarian cancer and its relationship with clinical outcomes is briefly reviewed. The kinds of immunotherapeutic strategies are summarized. The clinical trials investigating immunotherapy in recurrent ovarian cancer pa…
Gastrointestinal stromal tumors (GISTs): Focus on histopathological diagnosis and biomolecular features
Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract that are believed to originate from a neoplastic transformation of the intestinal pacemaker cells (interstitial cells of Cajal) normally found in the bowel wall or their precursors. Although the microscopic features have been known for a long time, the defining characteristic of GIST is the presence of the cell-surface antigen CD117 (KIT), which is demonstrated by immunohistochemistry. KIT, which is a growth factor transmembrane receptor, is the product of the proto-oncogene c-kit (chromosome 4). Surgical removal remains the only curative treatment for patients with GISTs. Tumor size, mitotic index,…
Ramucirumab and its use in gastric cancer treatment
Abstract: The inhibition of the mechanisms of tumor neo-angiogenesis represents a milestone that in the last 10 years has seen the advent of numerous molecules to target action against the vascular endothelial growth factor (VEGF). More recently, new molecules have been developed that inhibit tumor spread by the blockade of specific VEGF receptors (VEGFRs), thereby preventing the binding of a ligand to its receptor and the cascade of proliferative events downstream. Ramucirumab is a fully humanized IgG1 monoclonal antibody that performs its action by blocking the isoform 2 of the VEGF receptor (VEGFR-2). Numerous preclinical and clinical studies have demonstrated its activity in several sol…
Targeting apoptosis in solid tumors: the role of bortezomib from preclinical to clinical evidence.
The ubiquitin-proteasome pathway is the main proteolytic system present in the nucleus and cytoplasm of all eukaryotic cells. Apoptosis activation induced by ubiquitin-proteasome pathway inhibition makes the proteasome a new target of anticancer therapy. Bortezomib is the first proteasome inhibitor to be approved by the US FDA; in 2003 as a third line and in 2005 as a second line therapy for the treatment of multiple myeloma only. This review focuses on the use of bortezomib, not only in its therapeutic role but also, more specifically, in its biologic role and discusses the most recent applications of the drug in solid tumors, both at a preclinical and clinical level.
WHATSAPP MESSENGER AS A REAL-TIME TOOL FOR A LONG-DISTANCE ACTIVITY OF A MULTIDISCIPLINARY
CORRELATION BETWEEN FIBRONECTIN GENE EXPRESSION AND LOCAL TOXICITY INDUCED BY ADJUVANT INTRAVESICAL THERAPY
Triple negative breast cancer: shedding light onto the role of pi3k/akt/mtor pathway
// Daniela Massihnia 1,* , Antonio Galvano 1,* , Daniele Fanale 1 , Alessandro Perez 1 , Marta Castiglia 1 , Lorena Incorvaia 1 , Angela Listi 1 , Sergio Rizzo 1 , Giuseppe Cicero 1 , Viviana Bazan 1 , Sergio Castorina 2,3,** and Antonio Russo 1,** 1 Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy 2 Fondazione Mediterranea “G.B. Morgagni”, Catania, Italy 3 Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy * These authors have contributed equally to this work ** Both the authors are last name Correspondence to: Antonio Russo, email: // Keywords : ER, HER2, PI3K/AKT/mTOR inhib…
Biomarkers as Prognostic, Predictive, and Surrogate Endpoints
The improved understanding of tumor biology associated with the recent technological advancement has revealed a growing number of potential tumor biomarkers as candidate for clinical use, providing new opportunities for improving the management of cancer patients in all phases of care. Biomarkers have several clinical applications in oncology, including risk assessment for disease recurrence or early diagnosis in healthy population. After the advent of targeted therapies, a growing interest has been focused on their potential role as prognostic, predictive, and surrogate endpoints, in order to promote personalized strategies. The introduction of molecular biomarkers in clinical practice has…
Targeted Therapies in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is one of the main causes of death in patients affected by chronic liver diseases. The awareness of the biomolecular mechanisms underlying the complex carcinogenic process led to the development of targeted molecules, which are able to block this process. Sorafenib is a tyrosine-kinase inhibitor, and currently, it is the only drug approved by the US Food and Drug Administration (FDA) for the treatment of HCC. However, some studies have demonstrated the efficacy of single drug therapies or combination therapies. They showed an improvement with regard to overall survival, time to progression, and progression-free survival, although these therapies were not free …
Quality of Life in Patients With Severe Skin Reactions in Course of First-Generation Epidermal Growth Factor Receptor Inhibitors Monoclonal Antibodies (Our Experience With Cetuximab).
Background: Metastatic colorectal cancer (mCRC) with wild type expression of RAS and RAF genes can be treated with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, such as cetuximab, in combination with chemotherapy. Skin toxicity represents the most serious and frequent side effect in these patients. Skin manifestations occur in approximately 80% of patients. In this study, we investigated the consequences on body image and quality of life (QoL) of patients with severe skin toxicity. Methods: One hundred patients were enrolled with mCRC. All patients signed informed consent and completed questionnaires to assess QoL and body discomfort. Toxicity was assessed on Common Te…
KRAS and BRAF as prognostic biomarkers in patients undergoing surgical resection of colorectal cancer liver metastasis: A systematic review and meta-analysis.
3565Background: Clinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical treatment of li...
Characterization of γδ T cells in intestinal mucosa from patients with early onset or long standing inflammatory bowel disease and their correlation with clinical status
Abstract Background and Aims Inflammatory bowel disease [IBD] is a complex chronic inflammatory disease of the human gut with no clear aetiology. Traditionally, dysregulated adaptive immune responses play an important role even though accumulating evidence suggests a role also for innate immunity. Because of the well-known plasticity of γδ T cells, we investigated their percentage occurrence, phenotypic features and effector functions in the intestinal mucosa of early-onset and long-standing IBD patients, as compared to healthy subjects. Methods Fresh biopsies from 30 Crohn’s disease and ulcerative colitis patients were obtained and digested, and cells were analysed by flow cytometry. Resul…
Aminobisphosphonates as new weapons for gammadelta T Cell-based immunotherapy of cancer.
BACKGROUND: Activated V gamma 9 V delta 2 T cells are able to kill most tumour cells because of recognition by T cell receptor and natural killer receptors. OBJECTIVE: We discuss the possibility that the intentional activation of gammadelta T cells in vivo by aminobisphosphonates may represent a promising target for the design of novel and highly innovative immunotherapy in cancer patients. METHODS: The antitumoral effects of gammadelta T cells both in vitro and in vivo have been demonstrated suggesting a new therapeutic approach for translation into the clinical setting. RESULTS/CONCLUSION: V gamma 9 V delta 2 T lymphocytes represent a particularly interesting target for immunotherapeutic …
The Clinical Efficacy of Enzalutamide in Metastatic Prostate Cancer: Prospective Single-center Study
Background/Aim: To evaluate the effectiveness of enzalutamide in Italian patients with hormone-refractory metastatic castration-resistant prostate cancer, progressing after chemotherapy with docetaxel plus prednisone. Patients and Methods: A total of 60 patients were enrolled. Reduction in serum prostate-specific antigen (PSA) was assessed as the primary endpoint, while reduction in pain, safety, progression-free survival and overall survival represented secondary endpoints. Results: Enzalutamide was well tolerated, with a manageable toxicity profile and a modest objective response rate. A considerable difference in serum levels of PSA before and after treatment was observed. A significant …
Prognostic and predictive biomarkers for targeted therapy in NSCLC: For whom the bell tolls?
Introduction: The discovery of molecular biomarkers and the advent of targeted therapies have led to a radical change in the treatment of several tumors, including NSCLC. In the last few years, the number of molecular biomarkers has rapidly increased, and a growing interest has been recently focused on their potential prognostic and predictive value in clinical settings. Areas covered: This review describes all the molecular biomarkers with prognostic and predictive value in NSCLC, including both clinically approved biomarkers, and emerging biomarkers under investigation in clinical trials. Liquid biopsy and applications of circulating biomarkers are also described. Expert opinion: The onco…
Prognostic Relevance of Neutrophil to Lymphocyte Ratio (NLR) in Luminal Breast Cancer: A Retrospective Analysis in the Neoadjuvant Setting
The neutrophil to lymphocyte ratio (NLR) is a promising predictive and prognostic factor in breast cancer. We investigated its ability to predict disease-free survival (DFS) and overall survival (OS) in patients with luminal A- or luminal B-HER2-negative breast cancer who received neoadjuvant chemotherapy (NACT). Pre-treatment complete blood cell counts from 168 consecutive patients with luminal breast cancer were evaluated to assess NLR. The study population was stratified into NLRlow or NLRhigh according to a cut-off value established by receiving operator curve (ROC) analysis. Data on additional pre- and post-treatment clinical-pathological characteristics were also collected. Kaplan–Mei…
A phase II study of pegylated liposomal doxorubicin oxaliplatin and cyclophosphamide as second-line treatment in relapsed ovarian carcinoma
We carried out a phase II nonrandomized study to examine the level of activity of oxaliplatin, pegylated liposomal doxorubicin, and cyclophosphamide in a patient population with relapsed ovarian cancer pretreated with platinum derivatives and paclitaxel. Patients received oxaliplatin (85 mg/m2), pegylated liposomal doxorubicin (30 mg/m2), and cyclophosphamide (750 mg/m2). A total of 49 patients (39 assessable for toxicity and response) were enrolled in this trial. Neutropenia grade 3 was observed in six patients (15%) and anemia grade 3 in one patient (0.2%). Fatigue grade 1–2 occurred in 26 patients (66%), nausea/vomiting grade 1 in 23 patients (58%), and alopecia grade 1–2 in 19 patients …
Effects of anti-miR-182 on TSP-1 expression in human colon cancer cells: there is a sense in antisense?
Abstract: Objective: miRNAs are attractive molecules for cancer treatment, including colon rectal cancer (CRC). We investigate on the molecular mechanism by which miR-182 could regulate thrombospondin-1 (TSP-1) expression, a protein down-regulated in CRC and inversely correlated with tumor vascularity and metastasis. Background: MicroRNAs are small non-coding RNAs that regulate the expression of different genes, involved in cancer progression, angiogenesis and metastasis. miR-182, over-expressed in colorectal cancer (CRC), has like predictive target thrombospondin-1 (TSP-1), a protein inversely correlated with tumor vascularity and metastasis that results downregulated in different types of…
Studio pilota sul valore predittivo dei livelli plasmatici di 9 fattori angiogenetici nella selezione di pazienti candidati alla biopsia prostatica
To reduce the number of negative prostate biopsies in patients with elevated PSA serum levels represents a major challenge in urological oncology. Angiogenetic factors might be involved in initial stages of prostate cancer and might represent useful tools in patients' selection for prostate biopsy. The plasmatic levels of Angiopoietin-2, Follistatin, G-CSF, HGF, IL-8, Leptin, PDGF-BB, PECAM-1 and VEGF were measured by BioPlex immunoassay in patients undergoing prostate biopsy for palpable prostate nodule and/or elevated PSA levels (≥4 ng/mL). They were related with biopsy results. ROC curve analysis was exploited to test the diagnostic accuracy of each biomarker by AUC calculation. A potent…
Farletuzumab for NSCLC: Exploiting a well-known metabolic pathway for a new therapeutic strategy
Abstract: Introduction: The therapeutic options for NSCLC are limited barring targeted drugs, such as EGFR tyrosine-kinase inhibitors and anaplastic lymphoma kinase inhibitors, for patients bearing oncogenic mutations. Platinum-based chemotherapy remains the best strategy for most patients. New targeted drugs, including mAbs and small molecules, are currently under clinical investigation for treating NSCLC patients. Areas covered: The authors of this article focus on farletuzumab, a mAb targeting folate receptor, which has been studied in ovarian cancer and various other malignancies. In this review, the authors review its potential as therapy for NSCLC, because of the biological rationale …
Progression-free survival as a surrogate endpoint of overall survival in patients with metastatic colorectal cancer
Giuseppe Cicero,1 Rossella De Luca,1 Francesco Dieli2 1Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy; 2Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Italy Background: In many clinical trials designed to assess the efficacy of anticancer treatments, overall survival (OS) is often used as a primary endpoint despite its several points of weakness. Methods: This study evaluated the role of progression-free survival (PFS) in the first three lines of treatment as a potential surrogate endpoint of OS in patients with metastatic colorectal cancer (MCRC). One hu…
Impact of microRNAs in Resistance to Chemotherapy and Novel Targeted Agents in Non-Small Cell Lung Cancer
Despite recent advances in understanding the cancer signaling pathways and in developing new therapeutic strategies, non-small cell lung cancer (NSCLC) shows grim prognosis and high incidence of recurrence. Insufficient dis- ruption of oncogenic signaling and drug resistance are the most common causes of tumor recurrence. Drug resistance, in- trinsic or acquired, represents a main obstacle in NSCLC therapeutics by limiting the efficacy both of conventional che- motherapeutic compounds and new targeted agents. Therefore, novel and more innovative approaches are required for treatment of this tumor. MicroRNAs (miRNAs) are a family of small non-coding RNAs that regulate gene expression by sequ…
Optimizing the Choice for Adjuvant Chemotherapy in Gastric Cancer.
Advances in the management of gastric cancer have improved patient survival in the last decade. Nonetheless, the number of patients relapsing and dying after a diagnosis of localized gastric cancer is still too high, even in early stages (10% in stage I). Adjuvant systemic chemotherapy has been proven to significantly improve outcomes. In the present article we have critically reviewed the clinical trials that guide the current clinical practice in the adjuvant treatment of patients affected by resectable gastric cancer, focusing on the different approaches worldwide, i.e., adjuvant chemotherapy, adjuvant chemoradiotherapy, and perioperative chemotherapy. We also delineate the clinical–path…
In vivo manipulation of Vgamma9Vdelta2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patients.
The potent anti-tumour activities of gamma delta T cells have prompted the development of protocols in which gamma delta-agonists are administered to cancer patients. Encouraging results from small Phase I trials have fuelled efforts to characterize more clearly the application of this approach to unmet clinical needs such as metastatic carcinoma. To examine this approach in breast cancer, a Phase I trial was conducted in which zoledronate, a V gamma 9V delta 2 T cell agonist, plus low-dose interleukin (IL)-2 were administered to 10 therapeutically terminal, advanced metastatic breast cancer patients. Treatment was well tolerated and promoted the effector maturation of V gamma 9V delta 2 T …
The Risk of Toxicities from Trastuzumab, Alone or in Combination, in an Elderly Breast Cancer Population
<b><i>Background:</i></b> Breast cancer in the elderly is associated with high recurrence and death rates, due mostly to undertreatment. Human epidermal growth factor receptor type 2 (HER2) overexpression is infrequent in older patients. Trastuzumab-based chemotherapy is often withheld from elderly patients because of its cardiotoxicity. <b><i>Patients and Methods:</i></b> Medical records of consecutive HER2-positive breast cancer patients aged ≥70 years old treated between 2005 and 2010 in the participating centers were retrospectively reviewed. All patients underwent multidimensional geriatric assessment (MGA). <b><i>Results:<…
I tumori della mammella e/o dell’ovaio di tipo eredofamiliare: strategie di prevenzione nelle donne ad alto rischio
Numerosi fattori sono stati coinvolti nell’insorgenza del carcinoma mammario e dell’ovaio tra cui l’età, fattori ormonali e riproduttivi come l’età e il numero di gravidanze e l’utilizzo di contraccettivi orali e, in minor misura, fattori ambientali e stili di vita. Le possibilità per la gestione clinica delle pazienti considerate ad alto rischio di sviluppare carcinoma della mammella e/o dell’ovaio includono chirurgia profilattica (es. mastectomia bilaterale profilattica o ovarosalpingectomia bilaterale), chemioprevenzione (principalmente tamoxifene e raloxifene ma anche, più recentemente, inibitori dell’aromatasi nelle donne ad alto rischio in postmenopausa), cambiamenti nelle abitudini d…
Effects of PPARγ agonists on the expression of leptin and vascular endothelial growth factor in breast cancer cells.
The obesity hormone leptin has been implicated in breast cancer development. Breast cancer cells express the leptin receptor and are able to synthesize leptin in response to obesity-related stimuli. Furthermore, leptin is a positive regulator of vascular endothelial growth factor (VEGF) and high levels of both proteins are associated with worse prognosis in breast cancer patients. Peroxisome proliferator-activated receptor γ (PPARγ) ligands are therapeutic agents used in patient with Type 2 diabetes and obesity which have recently been studied for their potential anti-tumor effect. Here, we studied if these compounds, ciglitazone and GW1929, can affect the expression of leptin and VEGF in b…
Well-being among Italian medical oncologists: An exploratory study
<b><i>Background:</i></b> Recently, attention has been focused on physicians' stress and quality-of-life improvement. Due to their relationship with patients, oncologists in particular are overloaded physically, emotionally and psychologically. Previous studies showed that training of communication skills improves the satisfaction and well-being of physicians and patients. <b><i>Aims:</i></b> Our research investigates the relationship between work stress and engagement and personal well-being in physicians working in Italian hospitals. <b><i>Materials and Methods:</i></b> 176 physicians were included. Doctors filled out…
Vinflunine in Metastatic Urothelial Carcinoma of the Bladder in Progression after a Platinum-Containing Regimen
<b><i>Background:</i></b> Vinflunine is a microtubule inhibitor of the vinca alkaloid class approved for the treatment of urothelial bladder carcinoma after a platinum-containing regimen. <b><i>Methods:</i></b> To evaluate the effectiveness of vinflunine, we enrolled 80 subjects with a histologically confirmed diagnosis of metastatic urothelial bladder carcinoma that had previously undergone chemotherapy with a platinum-containing regimen and had measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST). The patients (<i>n</i> = 80) received vinflunine (Javlor®) every 3 weeks at 320 mg/m<sup>2&…
Gemcitabine and oxaliplatin combination chemotherapy in advanced biliary tract cancers
Background Biliary tract cancers are uncommon tumors with a poor prognosis and most patients present with invasive and inoperable disease at diagnosis. Chemotherapy represents a palliative treatment, with poor response rates and a median survival of less than 6 months. Oxaliplatin and gemcitabine have shown an interesting activity as single agents in this group of patients. Patients and methods We carried out a multicenter phase II study to evaluate the efficacy and safety of combined oxaliplatin and gemcitabine in locally advanced and metastatic biliary tract carcinoma. The schedule of chemotherapy included oxaliplatin 100 mg/m2 on day 1 and gemcitabine 1000 mg/m2 on days 1 and 8, every 21…
Zoledronic acid induces a significant decrease of circulating endothelial cells and circulating endothelial precursor cells in the early prostate cancer neoadjuvant setting
<b><i>Purpose:</i></b> Published data demonstrated that zoledronic acid (ZOL) exhibits antiangiogenetic effects. A promising tool for monitoring antiangiogenic therapies is the measurement of circulating endothelial cells (CECs) and circulating endothelial precursor cells (CEPs) in the peripheral blood of patients. Our aim was to investigate the effects of ZOL on levels of CECs and CEPs in localized prostate cancer. <b><i>Methods:</i></b> Ten consecutive patients with a histologic diagnosis of low-risk prostate adenocarcinoma were enrolled and received an intravenous infusion of ZOL at baseline (T0), 28 days (T28) and 56 days (T56). Blood samp…
Chemotherapy Sensitizes Colon Cancer Initiating Cells to Vγ9Vδ2 T Cell-Mediated Cytotoxicity
Colon cancer comprises a small population of cancer initiating stem cells (CIC) that is responsible for tumor maintenance and resistance to anti-cancer therapies, possibly allowing for tumor recapitulation once treatment stops. Combinations of immune-based therapies with chemotherapy and other anti-tumor agents may be of significant clinical benefit in the treatment of colon cancer. However, cellular immune-based therapies have not been experimented yet in the population of colon CICs. Here, we demonstrate that treatment with low concentrations of commonly used chemotherapeutic agents, 5- fluorouracyl and doxorubicin, sensitize colon CICs to Vc9Vd2 T cell cytotoxicity. Vc9Vd2 T cell cytotox…
Corrections to “Cetuximab rechallenge in metastatic colorectal cancer patients: how to come away from acquired resistance?”
Nessuno
Intraosseous gas distribution as a marker of postmortem interval
Abstract The postmortem interval is probably the most important puzzle piece in clarifying the circumstances in case of death occurred in unknown conditions. Over the years, radio-imaging modalities have proved their worth in forensic field, providing additional and significant improvements and findings. CT-scan is characterized by wide availability, fast scan times and sustainable healthcare costs. Detection of gas, hemorrhage and bone fractures are points of strength of CT-scan. A reliable evaluation of the post-mortem interval is interesting in the victims of a mass disaster, also following a natural disaster, for the individuation of responsibility in the efficiency of the help and assi…
Targeted Therapies in Hepatocellular Carcinoma
Abstract: The onset of hepatocellular carcinoma (HCC) is related to the development of non-neoplastic liver disease, such as viral infections and cirrhosis. Even though patients with chronic liver diseases undergo clinical surveillance for early diagnosis of HCC, this cancer is often diagnosed in advanced stage. In this case locoregional treatment is not possible and systemic therapies are the best way to control it. Until now sorafenib, a Raf and multi-kinase inhibitor has been the best, choice to treat HCC systemically. It showed a survival benefit in multicenter phase III trials. However the proper patient setting to treat is not well defined, since the results in Child-Pugh B patients a…
Geldanamycin and its derivatives as Hsp90 inhibitors
The Hsp90 molecule, one of the most abundant heat shock proteins in mammalian cells, maintains homeostasis and prevents stress-induced cellular damage. Hsp90 is expressed under normal conditions at a level of about 1-2 Percent of total proteins, while its expression increases 2-10 fold in cancer cells. The two main constitutively expressed isoforms of Hsp90 are known as Hsp90-alpha and Hsp90-beta, and their upregulation is associated with tumor progression, invasion and formation of metastases, as well as development of drug resistance. The Hsp90 is a key target for many newly established, potent anticancer agents containing Hsp90 N-terminal ATP binding inhibitors, such as geldanamycin, and…
Detection and quantification of mammaglobin in the blood of breast cancer patients: can it be useful as a potential clinical marker? Preliminary results of a GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.
BACKGROUND: Mammaglobin is expressed mainly in mammary tissue, overexpressed in breast cancer (BC) and rarely in other tissue. The aim of this study was to assess the sensitivity and specificity of transcript MGB1 detection and to evaluate the role of MGB1 as potential clinical marker for the detection of disseminated cancer cells in the blood of BC patients. PATIENTS AND METHODS: A consecutive series of 23 BC tissues, 36 peripheral blood BC samples and 35 healthy peripheral blood samples was prospectively recruited to investigate MGB1 expression by means of a quantitative Real Time RT-PCR assay. RESULTS: MGB1 overexpression in tissue samples of BC patients is significantly associated only …
Distinctive features of tumor-infiltrating γδ T lymphocytes in human colorectal cancer.
γδ T cells usually infiltrate many different types of cancer, but it is unclear whether they inhibit or promote tumor progression. Moreover, properties of tumor-infiltrating γδ T cells and those in the corresponding normal tissue remain largely unknown. Here we have studied features of γδ T cells in colorectal cancer, normal colon tissue and peripheral blood, and correlated their levels with clinicopathologic hallmarks. Flow cytometry and transcriptome analyses showed that the tumor comprised a highly variable rate of TILs (5–90%) and 4% γδ T cells on average, with the majority expressing Vδ1. Most Vδ1 and Vδ2 T cells showed a predominant effector memory phenotype and had reduced production…
Stabilizing versus Destabilizing the Microtubules: A Double-Edge Sword for an Effective Cancer Treatment Option?
Microtubules are dynamic and structural cellular components involved in several cell functions, including cell shape, motility, and intracellular trafficking. In proliferating cells, they are essential components in the division process through the formation of the mitotic spindle. As a result of these functions, tubulin and microtubules are targets for anticancer agents. Microtubule-targeting agents can be divided into two groups: microtubule-stabilizing, and microtubule-destabilizing agents. The former bind to the tubulin polymer and stabilize microtubules, while the latter bind to the tubulin dimers and destabilize microtubules. Alteration of tubulin-microtubule equilibrium determines th…
Circulating exosomal Hsp60 as a new marker of colon cancer.
The use of zoledronic acid in patients with bone metastases from prostate carcinoma: Effect on analgesic response and bone metabolism biomarkers
Zoledronic acid is a bisphosphonate that is effective in the treatment of complications of metastatic bone disease. We have carried out a perspective study on 24 consecutive patients with prostate cancer metastatic to bone to verify the effect of zoledronic acid on analgesic response and a possible relationship with the levels of bone metabolism biomarkers. Eligibility for this study required prostate cancer patients with metastatic bone disease and pain not controlled by analgesics. Patients were excluded from the study if they were receiving cytotoxic chemotherapy or radiation therapy within three months. Eighteen patients (75%) were considered responder to acid zoledronic, only 6 patient…
Germline copy number variation in theYTHDC2gene: does it have a role in finding a novel potential molecular target involved in pancreatic adenocarcinoma susceptibility?
Abstract: Objective: The vast majority of pancreatic cancers occurs sporadically. The discovery of frequent variations in germline gene copy number can significantly influence the expression levels of genes that predispose to pancreatic adenocarcinoma. We prospectively investigated whether patients with sporadic pancreatic adenocarcinoma share specific gene copy number variations (CNVs) in their germline DNA. Patients and methods: DNA samples were analyzed from peripheral leukocytes from 72 patients with a diagnosis of sporadic pancreatic adenocarcinoma and from 60 controls using Affymetrix 500K array set. Multiplex ligation-dependent probe amplification (MLPA) assay was performed using a s…
Risk Perception and Psychological Distress in Genetic Counselling for Hereditary Breast and/or Ovarian Cancer
International audience; Oncological Genetic Counselling (CGO) allows the identification of a genetic component that increases the risk of developing a cancer. Individuals' psychological reactions are influenced by both the content of the received information and the subjective perception of their own risk of becoming ill or being a carrier of a genetic mutation. This study included 120 participants who underwent genetic counselling for breast and/or ovarian cancer. The aim of the study was to examine the relation between their cancer risk perception and the genetic risk during CGO before receiving genetic test results, considering the influence of some psychological variables, in particular…
<p>Nab-paclitaxel in pretreated metastatic breast cancer: evaluation of activity, safety, and quality of life</p>
Objective Metastatic breast cancer (MBC) is an incurable disease; the treatment of this disease prolongs survival, improving the quality of life (QoL) with a balance between efficacy and toxicity of the treatment. In recent years, treatment with nab-paclitaxel has improved the already known antitumor activity of conventional paclitaxel, in terms of increased efficacy and better tolerability. The aim of this study was to evaluate nab-paclitaxel in Italian patients with MBC. Methods We conducted a retrospective analysis of 90 patients with histologically confirmed diagnosis of MBC. To evaluate the efficacy of nab-paclitaxel, overall survival (OS), progression-free survival (PFS), and overall …
Effects of erybuline/capecitabine (EC) treatment in very elderly women (VEW) with MBC.
e12508 Background: Eribuline mesylate, is widely prescribed for MBC pts alone or in combination with Capecitabine in patients pretreated with at least 1-2 lines of chemotherapy, including anthracyclines and taxanes (A&T). Elderly Patients (EP) develop rapid and sometimes fatal toxicity during treatments due to pharmacokinetic features of these drugs.A combination schedule (E+C) to evaluate its suitability for VEW with MBC patients ,was used in this study. Methods: Treatment plan: E 0.96 mg/sqm IV on d1 every 21d - C 900 mg/sqm bid d1-14 every 28d (Dose-adjustement if necessary was according to Kintzel-Dorr’s formula for elderly), schedule administration continued until progression or i…
Vγ9Vδ2 T cells as a promising innovative tool for immunotherapy of hematologic malignancies
The potent anti-tumor activities of γδ T cells, their ability to produce pro-inflammatory cytokines, and their strong cytolytic activity have prompted the development of protocols in which γδ agonists or ex vivo-expanded γδ cells are administered to tumor patients. γδ T cells can be selectively activated by either synthetic phosphoantigens or by drugs that enhance their accumulation into stressed cells as aminobisphosphonates, thus offering new avenues for the development of γδ T cell-based immunotherapies. The recent development of small drugs selectively activating Vγ9Vδ2 T lymphocytes, which upregulate the endogenous phosphoantigens, has enabled the investigators to design the experiment…
Linfomas malignos primários nas glandulas salivares
Primary malignant lymphomas in the salivary glands are relatively rare. Clinical presentation is not characteristic and the disease is often overlooked resulting in diagnosis and treatment delays. AIM: To stress the importance of the diagnostic process and combined management, we present a series of eight patients with malignant lymphoma of the parotid who were diagnosed only after surgery and managed with radiation and chemotherapy. METHODS: Retrospective series of patients with primary malignant lymphoma of the parotid gland managed with radiotherapy and diagnostic surgical partial resection. RESULTS: After treatment completion we achieved a loco-regional control rate of 87.5%. Toxicity w…
The role of microRNAs in cancer: diagnostic and prognostic biomarkers and targets of therapies
Introduction: miRNAs are noncoding RNAs that target specific mRNA with subsequent regulation of particular genes, implicated in various biological processes. In cancer, miRNAs could show a different expression from normal tissues. miRNAs have a role as oncogenes when they target tumor suppressor genes and similarly they are tumor suppressors when they target oncogenes. Areas covered: In this review, areas covered include the role of miRNAs in cancer diagnosis, prognosis and research for achievement of therapeutic strategies implicating miRNAs in oncology. As biogenesis of miRNAs is fundamental to understand their usefulness, this has also been discussed. Both miRNA expression profiles in ca…
A randomized phase II study of estramustine phosphate versus estramustine phosphate plus etoposide in hormone refractory prostate cancer (HRPC)
20632 Background: Docetaxel-based regimens represent the treatment of choice of HRPC. However, in some patients toxicity may be a concern and the quality of life may be compromised. The aim of this phase II randomized study is to investigate the efficacy and safety of low-dose chemotherapy regimen adopting a combination of EMP and VP16 in patients affected by HRPC. Methods: 54 HRPC patients were randomized between: arm A, daily oral standard dose EMP (10mg/kg) and arm B, low-dose EMP (3mg/kg) plus VP16 (25mg/mq) for 2 weeks followed by 2-weeks’rest. Systemic toxicity and hematologic exams were monitored every 2 weeks. Performance status, pain and analgesic use were evaluated according to WH…
Combining conventional chemotherapy and γδ T cell-based immunotherapy to target cancer-initiating cells.
Colon cancer comprises a small population of cancer initiating stem cells (CIC) that is responsible for tumor maintenance and resistance to anti-cancer therapies, possibly allowing for tumor recapitulation once treatment stops. Combinations of immune-based therapies with chemotherapy and other anti-tumor agents may be of significant clinical benefit in the treatment of colon cancer. However, cellular immune-based therapies have not been experimented yet in the population of colon CICs. Here, we demonstrate that treatment with low concentrations of commonly used chemotherapeutic agents, 5-fluorouracyl and doxorubicin, sensitize colon CICs to Vγ9Vδ2 T cell cytotoxicity. Vγ9Vδ2 T cell cytotoxi…
Treatment with abiraterone in metastatic castration-resistant prostate cancer patients progressing after docetaxel: a retrospective study.
The aim of this study was to evaluate abiraterone's efficacy in Italian patients affected with metastatic prostate cancer progressing after treatment with docetaxel. We conducted a retrospective analysis of 60 patients. Prostate-specific antigen (PSA) reduction in serum was the primary endpoint for evaluating the efficacy of abiraterone in combination with prednisone treatment, whereas reduced pain, safety, progression-free survival, response rate, and overall survival (OS) were secondary endpoints. A significant correlation was noticed between PSA response and OS. Further, the Index Bravais-Pearson (r) correlation allowed us to observe a significant negative interdependence between PSA res…
Clinical and biochemical markers of visceral adipose tissue activity: Body mass index, visceral adiposity index, leptin, adiponectin, and matrix metalloproteinase-3. Correlation with Gleason patterns 4 and 5 at prostate biopsy
Context: The correlation between aggressive prostate cancer and obesity mainly based on body mass index (BMI) and pathology after surgery remains controversial. Aims: The aim of the study was to correlate BMI, visceral adiposity index (VAI), and the plasmatic levels of leptin, adiponectin, and matrix metalloproteinase-3 (MMP-3), and biomarkers of adipose tissue function, with the detection of Gleason patterns 4 and 5 at biopsy. Subjects and Methods: Consecutive patients with prostate cancer at 12-core transrectal biopsy were enrolled. BMI, waist circumference (WC), blood samples to evaluate the plasmatic levels of triglycerides (TG) and high-density lipoproteins (HDL), adiponectin, leptin, …
Gene expression profiling of cumulus oophorus cells reveals altered pathways in patients with endometriosis
Evaluation of anxiety level in patients wating to undergo to diagnostic radiological exams
Aims and objectives Methods and materials Results Conclusion Personal information References
Characterization of Human γδ T Lymphocytes Infiltrating Primary Malignant Melanomas
T lymphocytes are often induced naturally in melanoma patients and infiltrate tumors. Given that gamma delta T cells mediate antigen-specific killing of tumor cells, we studied the representation and the in vitro cytokine production and cytotoxic activity of tumor infiltrating gamma delta T cells from 74 patients with primary melanoma. We found that gamma delta T cells represent the major lymphocyte population infiltrating melanoma, and both V delta 1(+) and V delta 2(+) cells are involved. The majority of melanoma-infiltrating gamma delta cells showed effector memory and terminally-differentiated phenotypes and, accordingly, polyclonal gamma delta T cell lines obtained from tumor-infiltrat…
A phase II study of oxaliplatin (O) and gemcitabine (G) first line chemotherapy in patients with advanced biliary tract cancers
Background: Biliary tract cancers are uncommon tumors with a poor prognosis and most patients (pts) present with invasive and inoperable disease at diagnosis. Chemotherapy represents a palliative treatment, but single or combination-drug schedules have demonstrated poor response rates with a median survival less than 6 months. Recently O and G have showed an interesting activity as single agents in this group of pts. Methods: We carried out a multicenter phase II study to evaluate the efficacy and safety of combined O and G in locally advanced and metastatic biliary tract carcinoma. The schedule of chemotherapy included O 100 mg/m2 on day 1 and G 1000 mg/m2 on days 1 and 8, every 21 days. I…
The molecular changes driving the carcinogenesis in Barrett's esophagus: which came first, the chicken or the egg?
Esophageal adenocarcinoma originates from columnar metaplastic epithelium of the distal esophagus. Various steps for this carcinogenetic process are known. Before the onset of high-grade dysplasia and adenocarcinoma, endoscopic surveillance is possible. However, because of the high cost of long-term surveillance, predictive factors for cancer are being evaluated to identify subjects with metaplasia who have a higher risk of developing malignancy. Molecular changes seem suitable for this purpose, but could require a high resource expenditure. While trying to identify the best predictive factors for cancer risk, molecular changes and differences in miRNA expression profile between the various…
Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer
Rossella De Luca,1 Livio Blasi,2 Massimiliano Al&ugrave;,2 Valerio Gristina,1 Giuseppe Cicero1 1Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy; 2Medical Oncology Unit, ARNAS Hospital Civico, Di Cristina, Benfratelli, Palermo, Italy Purpose: Pancreatic carcinoma is the neoplasia with the major mortality, and main standard treatments in this cancer increase survival but do not lead to complete recovery of the patient. The aim of this study was to evaluate the efficacy of Abraxane&reg; (nab-paclitaxel) in Italian patients with metastatic pancreatic cancer (MPC).Patients and methods: We conducted a retrospective …
An Update on the Role of Anti-EGFR in the Treatment of Older Patients with Metastatic Colorectal Cancer
Although colorectal cancer is increasingly being diagnosed in older patients, their number is largely underrepresented in phase II or III clinical trials. Consequently, guidelines and the SIOG recommendations are not sufficiently clear regarding the treatment of these patients, particularly when chemotherapy is combined with monoclonal antibodies (bevacizumab, cetuximab, and panitumumab). Targeted therapy based on the use of anti-epidermal growth factor receptors (EGFRs) is conditioned by the potential for increased toxicity, making it more difficult to treat an older, rat sarcoma virus (RAS) and B rapidly accelerated fibrosarcoma (BRAF) wild-type patient. In light of a more detailed charac…
Pilot Study on Predictive Value of Plasmatic Levels of 9 Angiogenetic Biomarkers in Selection of Patients Candidate to Prostate Biopsy
To reduce the number of negative prostate biopsies in patients with elevated PSA serum levels represents a major challenge in urological oncology. Angiogenetic factors might be involved in initial stages of prostate cancer and might represent useful tools in patients’ selection for prostate biopsy. The plasmatic levels of Angiopoietin-2, Follistatin, G-CSF, HGF, IL-8, Leptin, PDGF-BB, PECAM-1 and VEGF were measured by BioPlex immunoassay in patients undergoing prostate biopsy for palpable prostate nodule and/or elevated PSA levels (≥4 ng/mL). They were related with biopsy results. ROC curve analysis was exploited to test the diagnostic accuracy of each biomarker by AUC calculation. A poten…
A case of guillain-barre syndrome in a patient with non small cell lung cancer treated with chemotherapy
Guillain-Barré Syndrome (GBS) is a demyelinating polyneuropathy of probable autoimmune pathogenesis characterized by rapidly progressive symmetric paralysis. In the literature some cases of GBS associated with anticancer chemotherapy are reported. We present a case of a 55-year old woman who complained of progressive motor deficit in four limbs, areflexia in lower limbs and facial nerve paralysis one week after beginning cisplatin-gemcitabine chemotherapy for metastatic lung cancer. The cerebrospinal fluid analysis showed a strong positive Pandy reaction with 435 mg/dl total protein. The electromyography and the electroneuronography established the diagnosis of inflammatory demyelinating po…
Specific TP53 and/or Ki-ras mutations as independent predictors of clinical outcome in sporadic colorectal adenocarcinomas: results of a 5-year Gruppo Oncologico dell'Italia Meridionale (GOIM) prospective study
BACKGROUND: Although Ki-ras and TP53 mutations have probably been the genetic abnormalities most exhaustively implicated and studied in colorectal cancer (CRC) progression, their significance in terms of disease relapse and overall survival has not yet clearly been established. PATIENTS AND METHODS: A prospective study was carried out on paired tumor and normal colon tissue samples from a consecutive series of 160 previously-untreated patients, undergoing resective surgery for primary operable sporadic CRC. Mutations within the TP53 (exons 5-8) and Ki-ras (exon 2) genes were detected by PCR-SSCP analyses following sequencing. RESULTS: Mutation analyses of exons 5 to 8 of the TP53 gene showe…
Whatsapp messenger as a tool for the multidisciplinary management in everyday clinical practice
Introduction & Objectives Communication between doctors is traditionally conducted by written clinical charts. Mobile health is becoming an integral part of modern healthcare system, improving accessibility and quality of medical care. Recent papers suggest that an increasing number of doctors are using in their practice mobile tools to communicate clinical informations (1,2). The aim of our study was to verify the adoption of WhatsApp Messenger in everyday clinical practice to obtain a real-time multidisciplinary collaboration among medical centers located in different areas of the city. Material & Methods In January 2016 a WhatsApp Messenger group was created among 25 specialists:…
Nivolumab in metastatic melanoma: good efficacy and tolerability in elderly patients.
Nivolumab is an anti&ndash
TAS-102 in metastatic colorectal cancer (mCRC): efficacy, tolerability, and quality of life in heavily pretreated elderly patients: a real-life study
Background: TAS-102 is an oral monotherapy, combining trifluridine and tipiracil hydrochloride, indicated for the treatment of pretreated metastatic colorectal cancer (mCRC). The aim of this real-life study is to evaluate the efficacy and safety of TAS-102 in heavily pretreated elderly patients with mCRC whose disease has progressed with standard therapies. Methods: In this retrospective observational study, we enrolled 50 elderly patients >70 years of age (median age 78 years) with a diagnosis of mCRC who were previously treated or were not considered candidates for treatment with other available therapies. Patients aged >70 years with advanced colorectal cancer and with an ECOG perf…
Aminobisphosphonates as New Weapons for &#947; &#948; T Cell-Based Immunotherapy of Cancer
Several observations in mice and in humans have collectively laid the foundation for examining the potential of γ δ T cells to exert tumor immunotherapy. Human γ δ T cells can be activated in a non-MHC dependent fashion either by low molecular mass phosphoantigens, or by agents that provoke the accumulation of endogenous pyrophosphates such as isopentenylpyrophosphate. Among the latter, aminobisphosphonates are well-established in the clinic, and extensive data are available on the compounds antiangiogenic, antiosteolytic and pro-apoptotic properties. In this review we discuss on the possibility that the intentional activation of γ δ T cells in vivo by aminobisphosphonates may represent a p…
Raltitrexed plus levofolinic acid and bolus/continuous infusion 5-fluorouracil on a biweekly schedule for elderly patients with advanced colorectal carcinomas
BACKGROUND: The aim of the study was to evaluate the safety and efficacy of the raltitrexed/5-fluorouracil/levofolinic acid combination regimen as first-line chemotherapy for elderly patients with advanced/metastatic colorectal cancer. PATIENTS AND METHODS: Previously untreated patients with metastatic colorectal cancer received raltitrexed 2 mg/m(2) i.v. plus levofolinic acid and 5-fluorouracil according to the De Gramont' schedule given every 2 weeks as first-line chemotherapy. Patients were re-evaluated after six cycles and chemotherapy was continued up to tolerance or disease progression. RESULTS: Seventy patients aged >/=65 years were accrued from 11 centers between September 2001 and …
The gene expression profile of cumulus cells reveals altered pathways in patients with endometriosis
PURPOSE: The objective of this experimental study was to compare the global gene expression profile of CC of mature oocytes in 18 patients with severe endometriosis and CC in 18 control patients affected by a severe male factor. METHODS: For each group, the CC were pooled, RNA was extracted and a microarray performed. For validating the microarray, a quantitative real-time PCR was performed in the CC of an independent set of patients with endometriosis (n = 5) and controls (n = 7). RESULTS: 595 differentially expressed genes (320 down-regulated, 275 up-regulated, p < 0.05, fold change ≥1.5) were identified. The most significant changes were observed in genes involved in the chemokine signal…
Monoclonal antibodies in gastrointestinal cancers
Introduction: Among gastrointestinal cancers, colorectal and gastric neoplasms are the most frequent. The development of new targeted drugs improved the efficacy of systemic therapy in advanced stages of those malignancies. Areas covered: This review highlights the main biological processes implicated in gastrointestinal cancer development and progression, such as angiogenesis and epidermal growth factor receptor (EGFR) signaling pathway. On these bases, anti-EGFR and anti-vascular endothelial growth factor (VEGF) monoclonal antibodies in colorectal and gastric cancer are discussed. Data about further monoclonal antibodies in development are also reported. Expert opinion: The use of monoclo…
PD-L1 expression as predictive biomarker in patients with NSCLC: a pooled analysis
// Francesco Passiglia 1, * , Giuseppe Bronte 1, * , Viviana Bazan 1, * , Clara Natoli 2 , Sergio Rizzo 1 , Antonio Galvano 1 , Angela Listi 1 , Giuseppe Cicero 1 , Christian Rolfo 3 , Daniele Santini 4 , Antonio Russo 1 1 Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy 2 Department of Medical, Oral and Biotechnological Sciences, University “G. D’Annunzio”, Chieti, Italy 3 Phase I- Early Clinical Trials Unit, Oncology Department and Multidisciplinary Oncology Center Antwerp (MOCA), Antwerp University Hospital, Edegem, Belgium 4 Medical Oncology Department, Campus Biomedico, University of Rome, Rome, Italy * These auth…
HIF-1 is involved in the negative regulation of AURKA expression in breast cancer cell lines under hypoxic conditions
Numerous microarray-based gene expression studies performed on several types of solid tumors revealed significant changes in key genes involved in progression and regulation of the cell cycle, including AURKA that is known to be overexpressed in many types of human malignancies. Tumor hypoxia is associated with poor prognosis in several cancer types, including breast cancer (BC). Since hypoxia is a condition that influences the expression of many genes involved in tumorigenesis, proliferation, and cell cycle regulation, we performed a microarray-based gene expression analysis in order to identify differentially expressed genes in BC cell lines exposed to hypoxia. This analysis showed that h…
A headlight on liquid biopsies: a challenging tool for breast cancer management
Breast cancer is the most frequent carcinoma and second most common cause of cancer-related mortality in postmenopausal women. The acquisition of somatic mutations represents the main mechanism through which cancer cells overcome physiological cellular signaling pathways (e.g., PI3K/Akt/mTOR, PTEN, TP53). To date, diagnosis and metastasis monitoring is mainly carried out through tissue biopsy and/or re-biopsy, a very invasive procedure limited only to certain locations and not always feasible in clinical practice. In order to improve disease monitoring over time and to avoid painful procedure such as tissue biopsy, liquid biopsy may represent a new precious tool. Indeed, it represents a bas…
New findings on primary and acquired resistance to anti-EGFR therapy in metastatic colorectal cancer: Do all roads lead to RAS?
Abstract: Anti-epidermal growth factor receptor therapy with the monoclonal antibodies cetuximab and panitumumab is the main targeted treatment to combine with standard chemotherapy for metastatic colorectal cancer. Many clinical studies have shown the benefit of the addition of these agents for patients without mutations in the EGFR pathway. Many biomarkers, including KRAS and NRAS mutations, BRAF mutations, PIK3CA mutations, PTEN loss, AREG and EREG expression, and HER-2 amplification have already been identified to select responders to anti-EGFR agents. Among these alterations KRAS and NRAS mutations are currently recognized as the best predictive factors for primary resistance. Liquid b…
Does the Compliance to Intravesical BCG Differ between Common Clinical Practice and International Multicentric Trials?
<b><i>Introduction:</i></b> The aim of this study was to analyze the reasons for intravesical BCG interruption in clinical practice. BCG for at least one year is advocated as the best regimen to treat high-risk non-muscle invasive bladder cancer (NMIBC). However, almost 50% of patients don't complete it. Toxicity accounts for 10% of dropouts in international trials. <b><i>Materials and Methods:</i></b> Patients with T1HG NMIBC undergoing 1-year BCG were enrolled in this study. BCG was administered for one year. Toxicity and causes of treatment interruption were recorded. <b><i>Results:</i></b> A total of 411 patients we…
MicroRNAs in colorectal cancer stem cells: new regulators of cancer stemness?
Recently, the hypothesis that colorectal tumors originate from a subpopulation of cells called ‘cancer stem cells' (CSCs) or tumor-initiating cells, which exhibit stem-like features, has been confirmed experimentally in various human cancers. Several studies have confirmed the existence of colorectal CSCs (CRCSCs) and have demonstrated that this rare cell population can be isolated by the expression of specific cell surface biomarkers. MicroRNAs (miRNAs) are a class of small non-coding RNAs, which are crucial for post-transcriptional regulation of gene expression and participate in a wide variety of biological functions, including development, cell proliferation, differentiation, metabolism…
What are the Cancer Risks in BRCA Carriers Apart from Those Regarding the Breast and the Ovary?
Germline mutations in the tumor suppressor genes BRCA1 and BRCA2 predispose to familial breast and/or ovarian cancer. The lifetime risk of members of families with genetic predisposition depends on the mutations of susceptibility genes. BRCA1 mutations seem to confer the highest risk of developing neoplastic diseases. Apart from breast and ovarian cancer mutations in BRCA, related pathways are supposed to confer a smaller risk for additional cancers (colon, melanoma, pancreas, lymphoma, prostate, liver). All these tumors have an inherited component not necessarily associated with genetic susceptibility to BRCA genes. To date he main focus of this review has been argued still with difficulty…
P-42 Reduced-dose of doublet chemotherapy combined with anti-EGFR antibodies as treatment option in vulnerable older patients with metastatic colorectal cancer: A retrospective cohort study
Intravesical chemotherapy for intermediate risk non-muscle invasive bladder cancer recurring after a first cycle of intravesical adjuvant therapy
Context: The therapeutic strategy in intermediate risk (IR) non-muscle invasive bladder cancer (NMIBC) recurring after intravesical therapy (IT) is not well defined. Most patients are usually retreated by Bacillus Calmette-Guerin (BCG). Aims: To evaluate the efficacy of intravesical chemotherapy (ICH) given at recurrence after the first cycle of ICH in IR-NMIBC recurring 6 months or later. Settings and Design: Retrospective analysis of the efficacy of ICH given after previous IT. Materials and Methods: The clinical files of IR-NMIBC patients recurring later than 6 months after transurethral resection (TUR) and IT and retreated by IT were reviewed. The patients should be at intermediate risk…
How Much of Familial Breast Cancer Risk is Currently Explained by the Known Genes?
The need to answer the question “how much of the familial risk is currently explained by the known genes?” has increased ,and although BRCA1 and BRCA2 are considered the two major breast cancer (BC) susceptibility genes, they do not justify the entire percentage of all hereditary BC cases. The current consensus is that other BC predisposing genes could explain at least a portion of the remaining non-mutated familial cases, including not only other high- penetrance BC genes, but also moderate and low-penetrance genes. Considering these three different categories of genes, a gap of risk estimation in breast cancer can be observed. Moreover, different researchers tried to give significance to …
The Role of Couples' Attachment Styles in Patients' Adjustment to Cancer.
<b><i>Objective:</i></b> This study aimed to understand how psychological variables and attachment styles can contribute to improve effective and functional adjustment to the disease and promote better psychological well-being. <b><i>Methods:</i></b> A total of 176 participants (88 couples) took part in this research. One member of each couple attended surgery centers at the Oncology Department of the University Hospital of Palermo. Each participant had filled in 5 questionnaires assessing the variables couple relationships, quality of life, anxiety, depression, and psychosocial adjustment to illness. <b><i>Results:</i></b…
Targeting human {gamma}delta} T cells with zoledronate and interleukin-2 for immunotherapy of hormone-refractory prostate cancer.
Abstract The increasing evidence that γδ T cells have potent antitumor activity suggests their value in immunotherapy, particularly in areas of unmet need such as metastatic carcinoma. To this end, we initiated a phase I clinical trial in metastatic hormone-refractory prostate cancer to examine the feasibility and consequences of using the γδ T-cell agonist zoledronate, either alone or in combination with low-dose interleukin 2 (IL-2), to activate peripheral blood γδ cells. Nine patients were enlisted to each arm. Neither treatment showed appreciable toxicity. Most patients were treated with zoledronate + IL-2, but conversely only two treated with zoledronate displayed a significant long-te…