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Background Axillary staging (pN) is considered one of the most important prognostic factors in breast cancer patients. However, the Z0011 study data drastically reduced the number of surgical axillary dissections in a selected group of patients, limiting the prognostic information relating to axillary involvement to the sentinel lymph node (SLN). It is known that there is a relationship between SLN total tumour load (TTL) and axillary involvement. The objective of this study is to analyse the relationship between the TTL and outcomes in patients with early stage breast cancer. Patients and methods clinicopathological and follow-up data were collected from 950 patients with breast cancer between 2009 and 2010 on whom SLN analysis was conducted by molecular methods (One Step Nucleic Acid Amplification, Sysmex, Kobe, Japan). Results TTL (defined as the total number of CK19 mRNA copies in all positive SLN) correlates with disease free survival (HR, 1.08; p = 0.000004), with local recurrence disease free survival (HR = 1.07; p = 0.0014) and overall survival (HR: 1.08, p = 0.0032), clearly defining a low-risk group (TTL 2.5 × 104 CK 19 mRNA copies/µL). Conclusions SLN TTL permits the differentiation between two patient groups in terms of DFS and OS, independently of axillary staging (pN), age and tumour characteristics (size, grade, lymphovascular invasion). This new data confirms the clinical value of low axillary involvement and could partially replace the information that staging of the entire axilla provides in patients on whom no axillary lymph node dissection is performed. © 2017 The Authors

A 21-year old woman presented with a 2-month history of abdominal pain. The diagnostic work-up disclosed a 17-cm intraperitoneal mass. Biopsy showed islets containing small round cells surrounded by abundant desmoplastic stroma. Immunohistochemistry was strongly positive for desmin and weakly positive for vimentin and neuron-specific enolase. Pathological diagnosis was intraabdominal round cell desmoplastic tumor. The patient underwent an intensive schedule of high-dose alkylator-based chemotherapy, the P6 protocol, designed by the Pediatrics Division of the Memorial Sloan-Kettering Cancer Center. She had a partial response and subsequently underwent resection of the residual mass followed by high-dose chemotherapy with stem cell support. Ten months later, the patient had disease progression and is currently receiving second-line chemotherapy. Una mujer de 21 años consultó por dolor abdominal de dos meses de evolución. El estudio que se le practicó puso de manifiesto la existencia de una masa intraperitoneal de 17 cm. La biopsia demostraba la existencia de islotes de células pequeñas y redondas, rodeadas de abundante estroma desmoplásico. La inmunohistoquímica fue fuertemente positiva para desmina y débilmente positiva para vimentina y enolasa neuronal específica. Con estos hallazgos el diagnóstico anatomopatológico fue de tumor desmoplásico de célula pequeña intraabdominal. La paciente inició tratamiento con un esquema intensivo de altas dosis de quimioterapia basada en agentes alquilantes, de acuerdo con el Servicio de Pediatría del Memorial Sloan-Kettering Cancer Center, denominado protocolo P61. Tras el mismo presentó respuesta parcial siendo sometida a cirugía de las masa residuales y a continuación a quimioterapia de altas dosis con trasplante autólogo de médula ósea. Diez meses después la paciente presentó progresión de la enfermedad por lo que está recibiendo un asegunda línea de quimioterapia.

6 page, 3 figures. - PMID: 11479216, The development of new therapeutic strategies is essential for the management of gliomas, one of the most malignant forms of cancer. We have shown previously that the growth of the rat glioma C6 cell line is inhibited by psychoactive cannabinoids (I. Galve-Roperh et al., Nat. Med., 6: 313–319, 2000). These compounds act on the brain and some other organs through the widely expressed CB1 receptor. By contrast, the other cannabinoid receptor subtype, the CB2 receptor, shows a much more restricted distribution and is absent from normal brain. Here we show that local administration of the selective CB2 agonist JWH-133 at 50 μg/day to Rag-2−/− mice induced a considerable regression of malignant tumors generated by inoculation of C6 glioma cells. The selective involvement of the CB2 receptor in this action was evidenced by: (a) the prevention by the CB2 antagonist SR144528 but not the CB1 antagonist SR141716; (b) the down-regulation of the CB2 receptor but not the CB1 receptor in the tumors; and (c) the absence of typical CB1-mediated psychotropic side effects. Cannabinoid receptor expression was subsequently examined in biopsies from human astrocytomas. A full 70% (26 of 37) of the human astrocytomas analyzed expressed significant levels of cannabinoid receptors. Of interest, the extent of CB2 receptor expression was directly related with tumor malignancy. In addition, the growth of grade IV human astrocytoma cells in Rag-2−/− mice was completely blocked by JWH-133 administration at 50 μg/day. Experiments carried out with C6 glioma cells in culture evidenced the internalization of the CB2 but not the CB1 receptor upon JWH-133 challenge and showed that selective activation of the CB2 receptor signaled apoptosis via enhanced ceramide synthesis de novo. These results support a therapeutic approach for the treatment of malignant gliomas devoid of psychotropic side effects.

Sarcoidosis is a multisystem granulomatous disease of unknown cause with frequent pulmonary, ocular, and lymphatic system manifestations. Central nervous system involvement, although rare (1 to 5%), most commonly affects the cranial nerves. Cranial nerve VIII abnormalities occur in 20% of these patients and are associated with other neuropathies and organ or system involvement. We report a case of neurosarcoidosis that presented as isolated sudden sensorineural hearing loss and uveitis.

Squamous cell carcinomas can show different oncogenic alterations, histological patterns, and an unpredictable clinical behavior. We previously reported that the adenovirus E1a gene may induce sensitivity to DNA-damaging agents in mouse keratinocytes. In order to study whether E1a expression could be used as a therapeutic agent in different malignant cell lines carrying mutations on the p53 gene and other oncogenic alterations, we transfected and infected several murine and human carcinoma cell lines (HaCa4; MSC11A5; HeLa) with vectors containing the 13S or 12S E1a region. We evaluated the sensitivity to cisplatin (CDDP), doxorubicin (DOX) and gamma irradiation (RX) by the crystal violet method. The induction of apoptosis was assessed by flow cytometry and presence of DNA ladders in agarose gels. The expression of E1a and the tumor suppressor p53 protein was analysed by Western blotting. The carcinoma cell lines expressing E1a were about four- to tenfold more sensitive to CDDP and RX, respectively, than the control cells. Moreover, the reduction in cell viability and cell growth after exposure to CDDP or RX was very significant in the carcinoma cells expressing E1a. With these results, we conclude that expression of E1a may confer great sensitivity to DNA-damaging agents on squamous cell carcinoma cells independently of the p53 protein status and other oncogenic alterations.

The activation of oncogenes and the mutation/deletion of supressor genes may be involved in tumor heterogeneity. In an attempt to study tumor heterogeneity, we transformed cell lines from epithelial (PAM 212), mesenchymal (NIH-3T3), or melanocytic origin (L-BIOBR) with the wild type Ela oncogene. To make the cell lines tumorigenic, cells were infected with Harvey sarcoma virus carrying the v-H-ras oncogene. The transformed cells were injected into nude mice and the tumors studied by optical and electron microscopy. The tumors formed by v-H-ras-transformed cells consisted of epitheliod melanomas, spindle cells sarcomas and poorly-differentiated carcinomas, depending on the cell of origin. In contrast, the tumors obtained from cells also carrying the Ela oncogene showed a predominant small and undifferentiated cell pattem regardless of the cell of origin. We conclude that the Ela oncogene products induce a negative control of differentiation, independent of the cell type, and that tumors formed by cells carrying the Ela oncogene display an undifferentiated cell pattem.

We have previously reported that tumor formation of ras-transformed keratinocytes can be suppressed by dermal fibroblasts through production of a diffusible growth inhibitory factor of the transforming growth factor-beta (TGF-beta) family. Keratinocytes transformed by ras and E1a oncogenes or papilloma-derived keratinocytes transformed by a ras oncogene show concomitant resistance to dermal fibroblast tumor suppression and TGF-beta growth inhibition. We report here that dermal fibroblast tumor suppression is associated with a striking induction of squamous cell differentiation and that this effect is blocked in tumors resistant to dermal fibroblast inhibition. This experimental system strongly supports the notion that suppression of tumorigenicity and induction of a differentiated phenotype are closely associated events.

INTRODUCTION Cerebral gliomatosis is an infiltrating, non destructive process of glial type, with a diffuse growth pattern and great clinical variation in the initial symptoms. Confirmation of the diagnosis requires histological study of the lesion showing infiltration by well differentiated mature astrocytes (atypical forms are rare). We report three cases diagnosed by our department over the past five years. CASE REPORTS Case1. A 64 year old man presented with olfactory crises and right homonymous hemianopsia. On cerebral MR there was an extensive left occipital cortico subcortical lesion infiltrating the genum of the corpus callosum, with irregular uptake of contrast material. CASE REPORT 2: A 68 year old woman was admitted complaining of paresia of her right arm which had worsened over the past two months. On MR there was an extensive left paraventricular subcortical lesion, involving the anterior temporal and capsulo lenticular regions. Case 3. A 63 year old woman complained of staggering gait and headache. On examination she had a right facial palsy and intention tremor of her right arm. All the patients died. In all cases stereotactic biopsy confirmed the diagnosis of cerebral gliomatosis. CONCLUSIONS Cerebral gliomatosis is an infiltrating glial disorder with a poor prognosis. The clinical diagnosis is suggested on cerebral MR studies and confirmed on histological studies.