Search

Metabolic reprogramming is a hallmark of cancer which will provide tumor cells with all metabolites needed for growth and proliferation. Numerous oncogenes are responsible for a cellular metabolic reprogramming as part of their transforming role which illustrates the potential therapeutic advantage of targeting cancer metabolism. Anti-metabolites drugs, such as methotrexate or L-asparignase, have proven to be effective in many cancers and brought the proof of concept of cancer metabolism targeting. This justifies the development of new agents in this domain. When developing such molecules, many challenges are faced: to avoid toxicity linked to metabolism inhibition of normal cells, to anticipate redundancy of metabolic pathways which could abrogate efficacy, and to identify new targets and biomarkers. Therefore, cancer metabolism targeting is part of oncologic personalized medicine. Clinical and mostly pre-clinical researches are ongoing for glucose, glutamine, fatty acids, amino acids metabolism, and TCA cycle targeting. Genome scale Metabolic Modeling (GSMM) has been proven to be effective in identifying new metabolic targets. Cancer metabolism targeting is a promising way to treat cancer which has already proven efficacy with anti-metabolite drugs. At the moment, most of the data are preclinical but clinical trial of such agents will undoubtedly be set in the future. [ABSTRACT FROM AUTHOR]

The sole dysregulation of the cell cycle's molecular program does not explain the uncontrolled growth of cancer cells. Metabolism adaptation is also required. When differentiated (quiescent) cells depend on lactic fermentation in the absence of oxygen (and mitochondrial respiration when oxygen is present), cancer cells rely on lactic fermentation independently of oxygen availability. This metabolic adaptation is named as the Warburg effect. In this review, we will discuss the initial discovery of the Warburg effect and argue that it is not a simple adaptation to hypoxia. The Warburg effect emerges as a complex phenomenon and is now a hallmark of cancer due to its universality and specific molecular regulation. These recent discoveries open novel avenues for diagnostic and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Multidisciplinary meeting (MDM) should ensure a homogeneous management of the patients by following breast cancer guidelines. Are these guidelines really applied in MDM decisions? Patients and methods: We reviewed the last 200 cases of patients operated in our department for breast cancer. We searched for each case if MDM had been consulted, at which step of the management and if the decision was in accordance with our guidelines. Results: Mean age of the 200 patients was 56 (range 27–87)years old and 145 of them (72,5%) had an invasive breast cancer. All cases were presented to the MDM, 148 (74%) preoperatively and 200 (100%) postoperatively. Only four decisions did not follow our guidelines. In three cases, the decision was explained within the MDM report and in one case, the decision was not explained but could be understood. Discussion and conclusion: We found a significant relation between MDM decisions and our guidelines. However, complex cases require adapting the guidelines to the particularity and the wishes of the patients. [Copyright &y& Elsevier]

Angiogenesis constitutes a major process in cancer progression, especially by promoting the growth of malignant cells and dissemination of metastases. The development of anti-angiogenic targeted therapies has made significant progress over the last decade. Since the discovery of bevacizumab, numerous therapies have been designed. Among them, small molecules that inhibit the tyrosine-kinase activity of pro-angiogenic receptors such as VEGFR, are the most studied today. Current research focuses on the development of new targeted-therapies, able to inhibit the activity of several receptors at the same time and with a greater affinity. This article reviews the data on anti-angiogenic targetedtherapies, from available molecules to drugs still in the process of development. [ABSTRACT FROM AUTHOR]

Abstract: Angiogenesis is a crucial requirement for tumorogenesis, providing oxygen and nutrient supply necessary for tumor growth and metastasis. This is a complex phenomenon regulated by many factors that can now be targeted by novel anti-cancer therapies. Antiangiogenic approaches have shown positive results in clinical trials and are now approved as standard of care in medical oncology. Many clinical trials are evaluating antiangiogenic agents in association with radiotherapy. This review aims to summarize the knowledge useful to the understanding of these novel therapies and their potential in combination with radiotherapy. [Copyright &y& Elsevier]

Abstract: Metastatic tumors in the breast are quite rare and constitute 0.5 to 6% of all breast malignancies. They often occur in a polymetastatic context. The most frequent primitive tumors are lymphoma, leukaemia and malignant melanoma. The gastric origin is seldom reported. We report here the observation of a 40-years woman operated in urgency for an acute abdominal syndrome. A gastric tumor was discovered intraoperatively with ovarian metastasis and peritoneal carcinosis. The pathological examination revealed a gastric signet ring cell carcinoma with an infiltration of the right ovary. Four months later, the patient presented with a lump of the right breast. The histologic examination corresponded to a mammary metastasis by a signet ring cell carcinoma from stomach. The objective of our work is to discuss through this observation the anatomoclinical and evolutionary characteristics of breast metastasis. [Copyright &y& Elsevier]

Abstract: The first step for treatment of bone metastases is to confirm the diagnosis, particularly if there is only one localisation, so as to exclude a primary bone tumour. Surgery and percutaneous injection of acrylic cement are both efficient to relieve pain. Their indications and timing have to be discussed in pluridisciplinary staff. Long bones metastases have to be nailed before pathologic fracture. If there is suspicion of hypervascularisation, the lesion has to be embolized before any procedure. Treatment of spinal metastases with neurological impairment is an emergency. Paraplegia may be a consequence within a few hours. They have to be treated in an orthopedic or neurosurgery department with the experience of posterior and anterior approach of the spine. Surveillance may be useful to diagnose these metastases before neurological impairment. Depending from the type of cancer, the chemo- and radiotherapy sensibility, the number of metastases, the condition of the posterior wall of the vertebra and the general condition of the patient, different surgical treatments may be possible going from complete resection of the lesion to percutaneous injection of acrylic cement. Conventional radiotherapy is associated to surgery. Satisfactory results of such treatments justify greater involvement of orthopaedic surgery team in multidisciplinary staff. [Copyright &y& Elsevier]

Abstract: In clinically localized prostate cancers, the interest of pelvic lymphadenectomy is debated. Nevertheless, this intervention provides important information on disease prognosis (number of positive lymph nodes, tumoural volume, and extracapsular perforation of the affected ganglions); information that previously no other technique could provide. However, no consensus exists concerning patients who should benefit from pelvic lymphadenectomy and on the extent of this intervention. For most surgeons, decision making regarding ganglion curage is based on nomograms. According to these nomograms, patients with a level of prostate specific antigen (PSA)<10 ng/mL and a Gleason score<7 have a very low risk for ganglionic metastases; this is the reason why the benefit of pelvic lymphadenectomy remains controversial. Besides, most of these nomograms are based upon the results of standard lymphadenectomy (iliac vein and obturator fossa) with, subsequently, a related risk of imprecision. In addition, potential therapeutic benefit may be expected from extended ganglion curage, despite the fact that this is not clearly documented yet, due to the benign course of the disease. In other tumoural diseases (stomach cancer, breast cancer, colorectal cancer, blade cancer), on the contrary, survival and stage identification depend on the number of removed ganglions, thus on the extent of lymphadenectomy. [Copyright &y& Elsevier]

Abstract: Human papillomaviruses (HPV) are the most prevalent sexually-transmitted agents worldwide. HPV are small circular double-stranded DNA epitheliotropic viruses that exhibit either cutaneous or mucosal specificity. Most HPV infections are self-limiting and are spontaneously cleared within months or years. However, infections may persist and result in a variety of benign, pre-malignant and malignant tumors. Cytological and histopathological abnormalities associated with HPV infections of the male and female lower anogenital tract include condylomata, low-grade and high-grade squamous intraepithelial lesions which are incipient cancers, and squamous cell carcinomas. The modal time between HPV infection occurring in the late teens or early 20 s and precancer peaking around 30 years of age is 7-10 years. Women detected with invasive cancers tend to be an average 10 years older than women with high-grade disease. The natural history of cervical cancer reveals that infection with high-risk types may lead to low-grade or high-grade intraepithelial lesions. High-grade lesions may progress to cervical carcinoma if not treated. The purpose of screening, in addition to detecting cervical cancers at an early stage, is to detect and remove high-grade lesions and thus prevent the potential progression to cervical carcinoma. Early detection of cervical neoplasia is possible with regular Pap smears performed from 21 to 70 years of age. In case of abnormal Pap smear, a biopsy performed under colposcopy will allow the diagnosis of cervical lesion. Cancer of the cervix is the second leading cause of cancer related deaths among women across the world (3,400 new cases in France in 2000). [Copyright &y& Elsevier]

Abstract: The development of several new anti cancer agents has been made possible because of recent significant achievements in our global understanding of cancer biology. These new “targeted” agents selectively inhibit targets necessary for tumor cell growth and viability with little toxicity to normal cells compared to conventional cytotoxic agents. So far, the efficacy of many of these new promising agents when used alone treatment remains limited, it is likely that the optimal use of these agents could be obtained in combination with conventional agents such as radiation therapy. The potential benefit of these targeted therapies combined with irradiation seems important. They might offer the advantage of increasing the tumor response to radiation with no or little increase in normal tissue damage. Therefore, these new types of chemo-radiation approaches might respect the normal tissue versus tumor cell “therapeutic ratio”. These approaches can be sub divided in three sub groups: 1) Therapeutics targeting selectively one tumor related biochemical activity such as EGFR inhibitors. These approaches are efficient but one mutation of the target might render them inefficient. 2) Therapeutics directed against a widely expressed target. This is the case for anti Insulin Growth Factor-1 (IGF1R) interventions: IGF1R inhibition seems to specifically alter tumor cell viability with a minimal effect on normal cells viability. 3) Strategies which are not targeted against the tumor but the microenvironment, especially angiogenesis. This type of approaches seems to be applicable independently of tumor intrinsic biologic related factors. [Copyright &y& Elsevier]

Abstract: Small cell carcinoma of the ovary of the hypercalcemic type is a rare tumour, usually lethal and occurring almost exclusively in young patients. In the majority of described cases, signs of this lesion were revealed by the associated hypercalcemia or by virtue of the physical tumour bulk alone. We report the first case of ovarian small cell carcinoma of the hypercalcemic revealed by a severe acute pancreatitis in a 19-year-old patient. [Copyright &y& Elsevier]

Introduction: La metformine est un médicament couramment prescrit contre le diabète de type II, qui inhibe la production hépatique de glucose et augmente la captation de glucose par les muscles. Des études épidémiologiques ont montré que la metformine réduit le risque d’apparition de certains cancers. Cependant, son mode d’action sur les cellules cancéreuses reste inconnu. Nous avons étudié l’action de la metformine sur la croissance des lignées cancéreuses de la prostate humaine (DU145, PC-3, LNCaP) in vitro et in vivo. La metformine est un activateur de la voie AMPK (AMP activated Protein Kinase), un senseur de l’énergie cellulaire, celle-ci conduit à l’inhibition de mTOR connue pour induire la prolifération cellulaire et la synthèse protéique. Résultats: Nous montrons que la metformine n’induit pas l’apoptose mais un arrêt du cycle cellulaire en phase G0/G1 dans les cellules cancéreuses de prostate humaine. Cet arrêt s’accompagne par une forte diminution de la cycline D1 et de la phosphorylation de pRb mais également par une augmentation de l’expression de p27. Bien que la Metformine active la voie AMPK, celle-ci ne semble pas impliquée dans cet effet anti-prolifératif. En effet, l’inhibition de la voie AMPK à l’aide d’ARN interférent ne prévient pas l’effet de la metformine sur la croissance des cellules cancéreuses de la prostate. De façon intéressante, la metformine administrée par voie orale ou intrapéritonéale conduit à une diminution importante et significative de la croissance tumorale dans un modèle de xénogreffe chez la souris nude. De plus, comme observéin vitro, la metformine entraîne une diminution du niveau d’expression de la cycline D1 dans les tumeurs. Conclusion: Nous montrons que la metformine exerce un effet anti-néoplasique qui passe par un arrêt du cycle cellulaire. Ce travail pourrait ainsi expliquer les résultats observés par les récentes études épidémiologiques. [Copyright &y& Elsevier]