Gian Paolo Spinelli

Albumin-bound formulation of paclitaxel (Abraxane ABI-007) in the treatment of breast cancer.

Breast cancer is the most common type of malignancy diagnosed in women. In the metastatic setting this disease is still uncurable. Taxanes represent an important class of antitumor agents which have proven to be fundamental in the treatment of advanced and early-stage breast cancer, but the clinical advances of taxanes have been limited by their highly hydrophobic molecular status. To overcome this poor water solubility, lipid-based solvents have been used as a vehicle, and new systemic formulations have been developed, mostly for paclitaxel, which are Cremophor-free and increase the circulation time of the drug. ABI-007 is a novel, albumin-bound, 130-nm particle formulation of paclitaxel, free from any kind of solvent. It has been demonstrated to be superior to an equitoxic dose of standard paclitaxel with a significantly lower incidence of toxicities in a large, international, randomized phase III trial. The availability of new drugs, such as Abraxane®, in association with other traditional and non-traditional drugs (new antineoplastic agents and targeted molecules), will give the oncologist many different effective treatment options for patients in this setting.

Nanoparticle-based delivery of small interfering RNA: challenges for cancer therapy

During recent decades there have been remarkable advances and profound changes in cancer therapy. Many therapeutic strategies learned at the bench, including monoclonal antibodies and small molecule inhibitors, have been used at the bedside, leading to important successes. One of the most important advances in biology has been the discovery that small interfering RNA (siRNA) is able to regulate the expression of genes, by a phenomenon known as RNA interference (RNAi). RNAi is one of the most rapidly growing fields of research in biology and therapeutics. Much research effort has gone into the application of this new discovery in the treatment of various diseases, including cancer. However, even though these molecules may have potential and strong utility, some limitations make their clinical application difficult, including delivery problems, side effects due to off-target actions, disturbance of physiological functions of the cellular machinery involved in gene silencing, and induction of the innate immune response. Many researchers have attempted to overcome these limitations and to improve the safety of potential RNAi-based therapeutics. Nanoparticles, which are nanostructured entities with tunable size, shape, and surface, as well as biological behavior, provide an ideal opportunity to modify current treatment regimens in a substantial way. These nanoparticles could be designed to surmount one or more of the barriers encountered by siRNA. Nanoparticle drug formulations afford the chance to improve drug bioavailability, exploiting superior tissue permeability, payload protection, and the “stealth” features of these entities. The main aims of this review are: to explain the siRNA mechanism with regard to potential applications in siRNA-based cancer therapy; to discuss the possible usefulness of nanoparticle-based delivery of certain molecules for overcoming present therapeutic limitations; to review the ongoing relevant clinical research with its pitfalls and promises; and to evaluate critically future perspectives and challenges in siRNA-based cancer therapy.

Primary low-grade and high-grade gastric MALT-lymphoma presentation

Goal To assess the clinical and endoscopic presentation of primary gastric lymphoma. Background Remission rate and long-term survival in patients with gastric lymphoma mainly depend on disease stage at diagnosis. Series reporting clinical and endoscopic presentation of gastric lymphoma are generally small and heterogeneous. Study Systematic review with pooled-data analysis assessing clinical and endoscopic presentation of primary gastric lymphoma. Results Data regarding 2000 patients were collected. Overall, males were slightly more prevalent, alarm symptoms were absent in near half of the patients, lymphoma was diagnosed in a stage >I in one-third of the patients, and Helicobacter pylori infection was present in 88.8% of considered patients. At endoscopy, the ulcerative type was the most frequent presentation, although low-grade lymphoma was diagnosed on normal/hyperemic gastric mucosa in 9% of cases. Patients with high-grade lymphoma presented alarm symptoms (anemia and/or melena and/or hemorrhage, persistent vomiting, weight loss), an exophytic or ulcerative lesion, a stage III-IV, and a H. pylori negative status more frequently than low-grade lymphoma cases. Conclusions Our pooled-data analysis showed that gastric lymphoma is still disappointingly diagnosed in an advanced stage in a large number of patients. This is probably due to presence of nonspecific symptoms at initial clinical presentation and/or a normal appearing mucosa at endoscopic observation in the early stages.

Positron Emission Tomography (PET) radiotracers in oncology – utility of 18F-Fluoro-deoxy-glucose (FDG)-PET in the management of patients with non-small-cell lung cancer (NSCLC)

PET (Positron Emission Tomography) is a nuclear medicine imaging method, frequently used in oncology during the last years. It is a non-invasive technique that provides quantitative in vivo assessment of physiological and biological phenomena. PET has found its application in common practice for the management of various cancers.Lung cancer is the most common cause of death for cancer in western countries.This review focuses on radiotracers used for PET scan with particular attention to Non Small Cell Lung Cancer diagnosis, staging, response to treatment and follow-up

High-throughput microRNA profiling of pediatric high-grade gliomas

Background High-grade gliomas (HGGs) account for 15% of all pediatric brain tumors and are a leading cause of cancer-related mortality and morbidity. Pediatric HGGs (pHGGs) are histologically indistinguishable from their counterpart in adulthood. However, recent investigations indicate that differences occur at the molecular level, thus suggesting that the molecular path to gliomagenesis in childhood is distinct from that of adults. MicroRNAs (miRNAs) have been identified as key molecules in gene expression regulation, both in development and in cancer. miRNAs have been investigated in adult high-grade gliomas (aHGGs), but scant information is available for pHGGs. Methods We explored the differences in microRNAs between pHGG and aHGG, in both fresh-frozen and paraffin-embedded tissue, by high-throughput miRNA profiling. We also evaluated the biological effects of miR-17-92 cluster silencing on a pHGG cell line. Results Comparison of miRNA expression patterns in formalin versus frozen specimens resulted in high correlation between both types of samples. The analysis of miRNA profiling revealed a specific microRNA pattern in pHGG with an overexpression and a proliferative role of the miR-17-92 cluster. Moreover, we highlighted a possible quenching function of miR-17-92 cluster on its target gene PTEN, together with an activation of tumorigenic signaling such as sonic hedgehog in pHGG. Conclusions Our results suggest that microRNA profiling represents a tool to distinguishing pediatric from adult HGG and that miR-17-92 cluster sustains pHGG.

A phase II trial of a biweekly combination of paclitaxel and gemcitabine in metastatic breast cancer

BackgroundMany emerging new drugs have recently been trialled for treatment of early and advanced breast cancer. Among these new agents paclitaxel and gemcitabine play a crucial role, mostly in patients with relapsed and metastatic disease after failure of chemotherapy with antracyclines.MethodsA phase II study was started in order to evaluate the activity and toxicity of a combination of paclitaxel and gemcitabine in a biweekly schedule on metastatic breast cancer patients previously treated with antracyclines.ResultsTwenty-five patients received paclitaxel (150 mg/mq) by 3-hours infusion, followed by gemcitabine (2000 mg/mq) given as a 60 min i.v. infusion (day 1–14) for a maximum of eight cycles. In all patients treatment was evaluated for toxicity and efficacy; four patients (16%) achieved a complete response, 12 (48%) a partial response giving an overall objective response rate of 64%. Stable disease was documented in 5 patients (20%) and progressive disease occurred in 4 patients (16%).ConclusionThe schedule of treatment was safe and tolerable from a haematological and non-haematological point of view. These data confirm that the combination of gemcitabine and paclitaxel on a biweekly basis is an effective and well-tolerated regimen in breast cancer patients with prior therapeutic exposure to antracyclines.

Fertility drugs, reproductive strategies and ovarian cancer risk

Several adverse effects have been related to infertility treatments, such as cancer development. In particular, the relationship between infertility, reproductive strategies, and risk of gynecological cancers has aroused much interest in recent years. The evaluation of cancer risk among women treated for infertility is very complex, mainly because of many factors that can contribute to occurrence of cancer in these patients (including parity status). This article addresses the possible association between the use of fertility treatments and the risk of ovarian cancer, through a scrupulous search of the literature published thus far in this field. Our principal objective was to give more conclusive answers on the question whether the use of fertility drug significantly increases ovarian cancer risk. Our analysis focused on the different types of drugs and different treatment schedules used. This study provides additional insights regarding the long-term relationships between fertility drugs and risk of ovarian cancer.

Ovarian function, reproduction and strategies for fertility preservation after breast cancer

There is strong evidence that infertility is a dramatic and frequent side effect in men and women of childbearing age who are undergoing chemotherapy for their cancer treatment. This, severe and often underestimated complication heavily deteriorates the quality of life of affected patients and risks to reduce the therapeutic efforts and the compliance towards the suggested treatments. Moreover, cancer related infertility is still considered a marginal aspect of the quality of life in cancer patients. Reproductions preservation plays today an emerging role in the culture of industrialized countries and moves extraordinary interests from the scientific and economic points, of view. Unfortunately medical oncologists, surgeons and gynaecologists have little consideration, for this complication and often possess a limited knowledge about the clinical aspects of cancer, related infertility and the possibilities of prevention and treatment of cancer related gonadic failure. Since more young people are offered adjuvant treatments at earlier stages of cancer, the problem of, chemotherapy related gonadic toxicity has considerably increased in the last years. It is also important to consider the new opportunity derived from the assisted reproductive techniques available. From this point of view the treating physicians need to be able to make accurate assessments of risks and benefits of antineoplastic treatments in order to schedule the best approach to and to preserve the possibility of reproduction in their young patients. These aspects are more relevant in breast cancer patients, mainly in the early phase of the disease, due to the high probability to retain reproductive possibilities also after aggressive and integrated therapies.

Breast cancer risk after exposure to fertility drugs.

In recent years, there has been an increase in the diagnosis of infertility. In industrialized countries, approximately 15% of couples experience this problem today, with a negative impact on quality of life. For this reason, assisted reproductive technologies and other treatments, finalized to overcome infertility, have become very common in clinical practice. For a long time, different ovulation-inducing drugs have been used for ovarian follicle stimulation, either as independent therapies or treatments used during in vitro fertilization cycles. Despite this long-term use, the medical care for infertility gave rise to a lively debate about the potential risk of developing breast cancer that has never been settled. Many studies have been conducted to address this question; but their results have been, and still are, contradictory. The aim of this review is to determine the potential link between the use of fertility drugs and the risk of developing breast cancer in women treated for infertility.

Breast cancer metastatic to the pituitary gland: a case report

BackgroundMetastases to the pituitary gland are rare events, and usually indicate widespread malignant disease. The lung and the breast are the most common sites of primary tumors that metastasize to the pituitary gland.Metastases are more frequent in older patients and the most common symptoms at presentation are diabetes insipidus and visual alterations.Case presentation72-year-old white woman was treated for a breast carcinoma with right superoexternal quadrantectomy, radiotherapy, and hormone therapy. Twelve years later, the patient presented with bone pain, bilateral progressive visual decline, and onset of hypopituitarism. A diagnosis of secondary bone involvement and pituitary metastasis was made.ConclusionThis was an unusual disease course, and stresses the importance of intensive follow-up in patients with breast cancer even many years after the initial diagnosis This case emphasizes that diagnosis can be difficultand controversial when relapse occurs at uncommon sites.