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Context and Aims: Eribulin is used in taxane and anthracycline refractory HER2-negative metastatic breast cancers (MBC). Patients treated in pivotal clinical trials achieved low survival rates, therefore, the identification of prognostic criteria for long progression-free survival (PFS) is still an unmet medical need. In this study, we sought to determine potential prognostic criteria for long-term eribulin response in HER2-negative MBC., Methods: Our retrospective cohort includes female patients with HER2-negative MBC treated with eribulin in Franche-Comté, France. We defined a long-term response as at least 6 months of eribulin treatment. The primary endpoint was the analysis of criteria that differ according to the progression-free survival. Secondary outcomes concerned overall survival and response rate., Results: From January 2011 to April 2020, 431 patients treated with eribulin were screened. Of them, 374 patients were included. Median PFS was 3.2 months (2.8-3.7). Eighty-eight patients (23.5%) had a long-term response to eribulin. Four discriminant criteria allowed to separate PFS in 2 arms (PFS < 3 months or > 6 months) with a 78% positive predictive value: histological grade, absence of meningeal metastasis, response to prior chemotherapy, and OMS status. We have developed a nomogram combining these 4 criteria. Median overall survival was 8.5 months (7.0-9.5)., Conclusion: Eribulin response in MBC can be driven by clinical and biological factors. Application of our nomogram could assist in the prescription of eribulin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Although useful prognostic and predictive insights can be gained from patient and tumour characteristics in early-stage breast cancer, it is not always straightforward to predict the likely risk of recurrence for each individual patient following breast surgery. One of the most difficult challenges faced by clinicians is identifying patients who may benefit most from adjuvant chemotherapy, and distinguishing these cases from those where endocrine therapy may be sufficient for cure. Genomic tests such as the Oncotype DX ® Breast Recurrence Score ® Assay have been developed to provide a robust and clinically validated assessment of a patient's individual tumour signature. The Oncotype DX Assay is included in treatment guidelines for estimating both the risk of distant recurrence and predicting adjuvant chemotherapy benefit for early-stage breast cancer patients with human epidermal growth factor receptor 2-negative, oestrogen-receptor positive, and axillary lymph node negative or positive (1-3 positive nodes) disease. In this article, we review unmet needs for prognostication and prediction in early-stage breast cancer, and consider how the information provided by the Recurrence Score is complementary to that gained from the assessment of more traditional clinicopathologic criteria. Routine use of the assay in clinical practice, limitations and possible future directions are also discussed., (Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: Pain management is a major public health problem, especially in oncology. In order to assess professional practice, the IRFC-FC conducted a survey amongst patients with metastatic osteophilic solid tumor in Franche-Comté. The aims were to assess the pain prevalence, and its characteristics, its management and its impact on patients' quality of life in patients in pain., Methods: An observational, prospective and multicenter survey was conducted using a self-report questionnaire. Patients with metastatic breast or prostate cancer managed in 5 day-hospitals of the IRFC-FC over a period of three months were included., Results: Two hundred thirty-three questionnaires were analyzed. Pain prevalence rate was 48.5%. Three quarters of patients in pain had chronic background pain, moderate to severe, with or without breakthrough pain. Considering their pain intensity and their analgesic therapy, 42.0% of patients seem to have an inadequate treatment. Eighty-five percent of treated patients reported to be compliant and felt that their pain was well managed despite a strong impact on their quality of life., Conclusion: The setting of a specific clinical pathway is essential to secure the standardized, optimal and efficient management of patients in pain. The assessment of patient satisfaction and quality of life must be integrated in clinical practice to identify patients in pain for which the treatment is inappropriate., (Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Takotsubo syndrome is a stress cardiomyopathy, characterized by reversible left ventricle (LV) apical ballooning in the absence of significant angiographic coronary artery stenosis. The frequent association with emotional stress suggests in this disease an autonomic nervous system involvement. We could think that a therapeutic treatment targeting heart sympathetic dysfunction could be of crucial importance., Methods: From January 2010 to June 2012, 886 patients were consecutively evaluated at Cardarelli Hospital, Naples, Italy. Among these, 48 patients met takotsubo cardiomyopathy (TCM) criteria. Each patient was assessed with history and physical examination, 12-lead electrocardiogram, serum troponin, coronary arteriography, and left ventricular angiogram, perfusion myocardial scintigraphy with technetium 99m, with echocardiography and 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. At discharge, the surviving patients were randomly assigned to α-lipoic acid (ALA) treatment (600mg once daily) or placebo. Following discharge, after the initial TCM event, patients returned to our outpatient clinic at Internal Medicine of the Second University Naples for the follow-up evaluation quarterly until 12 months. Routine analysis, myocardial damage serum markers, oxidative stress serum markers, pro-inflammatory cytokines, and sympathetic tone activity were evaluated in all patients., Results: ALA administration improved MIBG defect size at 12 months compared to placebo., Conclusions: Adrenergic cardiac innervation dysfunction in TCM patients persists after previous experience of transient stress-induced cardiac dysfunction. ALA treatment improves the adrenergic cardiac innervation. This study evaluates whether sympatho-vagal alterations are TCM event-related., (Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Eribulin gained its approval in March 2011 for the treatment of patients with locally advanced or metastatic breast cancer (MBC) whose disease has progressed despite anthracycline and taxane-containing regimens. This study retrospectively assessed the efficacy, safety and cost of this treatment for all patients with MBC treated by eribulin in Franche-Comté. Ninety-four patients received eribulin between July 2006 and October 2013. The median age was 62 years (35-83). Median overall survival was 10.3 months [95% CI: 7.6 to 17.9]. Median progression-free-survival was 3.8 months [95% CI: 2.9 to 5.0]. Clinical benefit was obtained in 55% evaluable patients [95% CI: 43.1 to 66.9] by RECIST criteria. Most common grade 3-4 adverse events (AEs) were neutropenia (38%), asthenia (10%) and peripheral neuropathy (7%). Median cost of the treatment was 9767 € per patient (6344-17,517). This analysis found similar results to the EMBRACE study despite less selected population. A medico-economic evaluation cost-utility type would assess the effectiveness of this strategy compared to standard treatments., (Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: The present review was conceived for describing the differences in biodistribution and diagnostic performance of two types of (18)F-radiolabeled choline for positron emission tomography (PET) imaging in prostate cancer (PCa), such as fluoromethylcholine (FCH) and fluoroethylcholine (FEC)., Materials and Methods: A collection of published data about two radiopharmaceutical agents was made by using PubMed, Web of Knowledge databases and Trip Database, and then a critical revision was discussed., Results: FCH was injected in 338 and 1164 patients, while FEC was injected in 20 and 139 patients, respectively for basal staging and re-staging. The diagnostic performances of FCH and FEC for the detection of lymph node metastasis before the surgical approach are typically around 50% or less and between 0% and 39%, respectively. Conversely, both the tracers appear useful for the detection of recurrent PCa in case of increase in absolute PSA value or in case of high levels of PSA velocity and PSA doubling time (sensitivity ranged between 42.9% and 96% for FCH and between 62% and 85.7% for FEC)., Conclusions: In according with the available information, FCH appears to be a more appropriate radiocompound as compared to FEC, although more comparative data are mandatory. A well designed and prospective trial for the evaluation of biokinetic data and diagnostic performance of both radiopharmaceutical agents seems essential., Advances in Knowledge and Implication for Patient Care: FCH seems to be an appropriate radiopharmaceutical agent as compared to FEC. Anyway both the radiocompounds are useful in the evaluation of recurrent disease in case of a serial increase in PSA value and their performance improves when a correct preparation and acquisition protocol is employed., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Hematopoietic cell transplantation (HCT) is a curative treatment for hematological malignancies. This therapeutic approach is associated with a profound immune deficiency and an increased rate of opportunistic infections. Nocardiosis is a rare bacterial infection occurring mainly in patients with deficient cell-mediated immunity, such as AIDS patients or transplant recipients. Diagnosis of nocardiosis can be challenging, as signs and symptoms are non-specific. Routine prophylaxis with trimethoprin/sulfamethoxazole (TMP/SMZ) does not prevent the risk of infection. Between May 2001 and December 2009, five cases of nocardiosis were diagnosed from the 366 allogeneic HCT recipients in our centre. Four patients developed a disseminated nocardiosis within the first year after HCT. The fifth patient presented a localized cutaneous nocardiosis. In disseminated cases, median total CD4+ T-cells were below 100 cells/μL. Naive CD4+ CD45RA+/RO- T-cells were almost undetectable. CD8(+) T-cells and NK cells were below the normal range and CD19+ B-cell reconstitution was completely deficient. In a localized case, we observed a lack of naive thymic emigrants CD4+ CD45RA+/RO- T-cells., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background: Squamous cell carcinoma of the anal canal (SCCA) is a rare disease, mostly diagnosed at early stage. After concurrent chemoradiation (CRT) with mitomycin C and 5-fluorouracil (5FU), local or metastatic recurrences occur in >20% of the patients. After treatment failure, cisplatin (CDDP)-based chemotherapy is the standard option, but complete response (CR) is a rare event and the prognosis remains poor., Patients and Methods: Eight consecutive patients with advanced recurrent SCCA after CRT were treated with DCF regimen (docetaxel 75 mg/m(2) day 1, CDDP 75 mg/m(2) day 1 and 5FU at 750 mg/m(2)/day for 5 days every 3 weeks). Tumour samples were analysed for human papillomavirus (HPV) genotyping, as well as p16 and p53 expression., Results: After a median follow-up of 41 months, the overall survival rate at 12 months was 62.5% (95% CI 22.9-86.1 months). Four patients achieved a complete remission and remain relapse-free at the time of analysis with a progression-free survival of 19, 33, 43 and 88 months. Three of these patients underwent surgery for all involved metastatic sites. For all of them, pathological CR was confirmed. DCF regimen appeared feasible in these patients previously exposed to pelvic CRT, and no grade IV toxicity occurred. All patients in complete remission had HPV-16-positive SCCA, while HPV could only be detected among 50% of the non-responding patients. Of interest, immunohistochemical study revealed a p16(+)/p53(-) phenotype in these patients, while none of non-responders expressed p16., Conclusion: The high level of complete and long-lasting remission among SCCA patients treated with DCF regimen supports the assessment of this strategy in prospective cohorts.

Background: We examined the effects of peri-procedural intensive glycemic control during early percutaneous coronary intervention (PCI) on the number and differentiation of endothelial progenitor cells (EPCs) and myocardial salvage (MS) in hyperglycemic patients with first ST-elevation myocardial infarction (STEMI)., Methods and Results: We conducted a randomized, prospective, open label study on 194 patients with STEMI undergoing PCI: 88 normoglycemic patients (glucose < 140 mg/dl) served as the control group. Hyperglycemic patients (glucose ≥140 mg/dl) were randomized to intensive glycemic control (IGC) for almost 24 h after PCI (n = 54; 80-140 mg/dl) or conventional glycemic control (CGC, n = 52; 180-200 mg/dl). EPC number, differentiation, and SIRT1expression were assessed immediately before, 24 h, 7, 30 and 180 days after PCI. The primary end point of the study was salvage index, measured as the proportion of initial perfusion defect (acute technetium-99m sestamibi scintigraphy, performed 5 to 7 days after STEMI) and myocardium salvaged by therapy (6 months after STEMI). Hyperglycemic patients had lower EPC number and differentiation and lower SIRT1 levels than normoglycemic patients (P < 0.01). After the insulin infusion, mean plasma glucose during peri-procedural period was greater in CGC group than in IGC group (P < 0.001). The EPC number, their capability to differentiate, and SIRT1 levels were significantly higher in IGC group than in CGC, peaking after 24 h (P < 0.01). In the IGC group, the salvage index was greater than in patients treated with CGC (P < 0.001)., Conclusions: Optimal peri-procedural glycemic control, by increasing EPC number and their capability to differentiate, may improve the myocardial salvage., (© 2013. Published by Elsevier Ireland Ltd. All rights reserved.)

Breast cancer is a heterogenic cancer being characterized by a variability of somatic mutations and in particular by different receptor expressions, such as estrogen, progesterone and human epidermal receptor. These phenotype characteristics play a crucial role in determining tumour response to various chemotherapies and other treatments and in the development of resistance to therapies. Positron emission tomography (PET) as a nuclear medicine technique, has recently demonstrated the advantages in determining the severity of disease and in evaluating the efficacy of treatments in a variety of neoplasm, including breast cancer. Because this procedure is able to pinpoint molecular activity within the body, it offers the potential to identify disease in its earliest stages as well as a patient's immediate response to therapeutic interventions in a non-invasive way. In this paper we performed an extended view about the correlation between molecular factors of breast cancer and PET tracers; in particular, we focalized our attention on their possible advantages in terms of 1) early detection of primary or recurrent cancer; 2) as a guide for target therapies and 3) for the evaluation of response to specific and now-available molecular treatments., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Castration resistant prostate cancer occurs when patients experience disease progression despite appropriate hormonal manipulations. In these patients, chemotherapy remains standard treatment. Preclinical and clinical data have demonstrated the potential utility of an immunotherapy-based approach for the treatment of prostate cancer (PC). The phase III trial (IMPACT) has recently reported an advantage for Sipuleucel-T over placebo, with an overall survival 4.1 months superior to placebo. Sipuleucel-T is also the first FDA-approved immunotherapy for prostate cancer. These promising results need to be confirmed with other large studies and within previous step of PC. Neoplasic cells can escape immune responses by multiple mechanisms. A better knowledge of these mechanisms is of major concern for the future development of new immunotherapies approach.

EGFR may be considered as an old target, which can be inhibited both by monoclonal antibodies and tyrosine kinase inhibitors. Those molecular targeted strategies are now approved in a wild range of tumors: colorectal cancer, lung cancer, pancreatic cancer and head and neck cancer. This paper proposes to describe the development of anti-EGFR drugs, highlighting several strategies points. Predicting biomarkers have been extensively studied for these agents, sustaining the hallmarks of the development of molecular targeting drugs.

Scientific knowledge on gastrointestinal stromal tumors (GIST) has highly progressed over the last 10 years. The molecular bases of oncogenic transformation, KIT activating mutations, were identified in 1998 by Hirota et al. The product of KIT proto-oncogene, KIT protein, is a transmembrane receptor with tyrosine kinase activity. Tyrosine kinase inhibitors targeting these mutated activated kinases, namely imatinib and more recently sunitinib, nilotinib, masitinib or sorafenib, have deeply modified GIST prognosis. Molecular biology in GIST is now becoming a routine tool for treatment selection. In patients with advanced GIST, imatinib should be given until progression, and then, other tyrosine kinase inhibitors targeting KIT should be used. In the adjuvant setting, the optimal duration of imatinib treatment remains unknown.

RAS proteins are among the first proteins to demonstrate a crucial implication in the cell cycle regulation. The RAS signalling pathway plays a key role in the regulation of cell cycle through the activation of numerous downstream pathways including the RAF/MEK/ERK, PI3K/AKT/mTOR, RAL and PKC pathways. These pathways are involved in gene transcription, regulation of cell survival and angiogenesis. As the RAS signalling pathway was shown to be altered in several cancers, molecularly targeted agents that trigger various components of this pathway have been evaluated in clinical practice. This paper first reviews the regulation processes of the RAS protein in cancer, as well as RAS downstream main signalling pathways. Therapeutic approaches to target RAS or some of its effectors are then detailed. Finally, the ability of RAS mutations to predict response to EGFR-targeting agents is discussed in the context of colorectal and lung cancers.

Diabetic cardiomyopathy is a ventricular dysfunction in the absence of coronary artery disease, valvular or hypertensive heart disease. The mechanisms underlying diabetic cardiomyopathy may involve metabolic disturbances, myocardial fibrosis, small vessel disease, microcirculation abnormalities, cardiac autonomic neuropathy and insulin resistance. Diagnostic problems emerge because no specific disease pattern characterizes the disease and because there may be coexistence in diabetes of coronary artery disease and hypertension as independent but compounding causes of biochemical, anatomical and functional alterations impairing cardiac function. In this paper we will review the role of nuclear imaging today, concentrating on the diagnostic capabilities of radionuclide ventriculography, to study the effect of insulin resistance and, more extensively, gated-single photon emission computed tomography with Tc-99m labelled agents. A broad analysis will be dedicated to: 1) positron emission tomography using perfusion agents, with the potential to quantify resting and stress blood flow and coronary flow reserve; 2) radionuclide procedures evaluating aerobic and anaerobic cardiac metabolism; and 3) cardiac neurotransmission imaging, studying the autonomic neuropathy., ((c) 2009 Elsevier B.V. All rights reserved.)

We report a novel method for preparing samples for laser capture microdissection. The procedure described here permits extraction of intact RNA while preserving morphology, thus being suitable both for identification of specific cells and for analysis of their gene expression. The method is applicable to both mouse embryos and human tumors and may improve the preparation of cDNA libraries from specific cell types without interfering with histological diagnosis., ((c)2001 Elsevier Science.)

The effect of L-acetyl carnitine (L-AC) on cerebral blood flow (CBF) was evaluated in 20 patients with chronic cerebrovascular disease, who suffered an ischaemic stroke at least 6 months before the study. All patients performed a CT scan and were investigated with xenon-133 by brain dedicated single photon emission computed tomography (SPECT, Tomomatic 32, Medimatic Inc., Copenhagen). A single high dose (1.5 g) of L-acetyl carnitine was intravenously administered to 10 patients, while sodium acetate as placebo was injected to 10 other subjects. Cerebral blood flow (ml/min x 100 g) was evaluated before and 45 min after the injection. No changes were observed after placebo injection (43 +/- 12 ml/min x 100 g versus 43 +/- 10 ml/min x 100 g). CBF increased (from 42 +/- 9 ml/min x 100 g to 46 +/- 9, P less than 0.05) in both ipsilateral and contralateral hemisphere, the ischaemic area, but not in the stroke corresponding zone. It was concluded that L-acetyl carnitine at the i.v. dosage of 1.5 g acutely enhanced CBF in patients with chronic cerebral infarct.

We investigated the effects of the antimycotic agent amphotericin B (AmB) on the phagocytic activity of the isolated perfused rat liver. At a concentration of 5 microM, the drug markedly reduced the clearance of latex beads by the liver as compared to control preparations. Scanning electron microscopy observations showed that latex beads were attached only to Kupffer cells. A liver scan performed infusing 99Tc-colloidal albumin showed that AmB depressed the uptake of the colloid in all hepatic lobes, with no focal defects. Both in control and AmB experiments no trypan blue uptake occurred. The pretreatment of the perfused liver with the calcium antagonist nifedipine prevented the decrease in phagocytosis induced by AmB. In addition, AmB had no effect on livers perfused with a Ca2(+)-free medium. A decrease in the phagocytic capacity of the perfused liver was also observed after the administration of the Ca2(+)-ionophore A23187. The observations suggest that AmB may exert an intrinsic toxicity on the Kupffer cells, which is, at least in part, responsible for the decrease in phagocytosis induced by the drug. This effect may be of relevance to clinical situations and deserves careful consideration.