Analyse des délais de prise en charge des cancers thoraciques : étude prospective

RésuméIntroductionLe cancer broncho-pulmonaire est la première cause de décès par cancer en France. Son diagnostic est le plus souvent tardif, alors que le délai entre le début des symptômes et la prise en charge est considéré comme un facteur aggravant.Matériel et méthodesNotre étude prospective a recueilli les différentes dates de prise en charge de 139 patients consécutifs bénéficiant d’un traitement primaire pour un cancer thoracique dans notre hôpital entre novembre 2008 et mai 2009. L’objectif de cette étude était d’évaluer différents délais de prise en charge des patients porteurs d’un cancer thoracique quelle que soit sa prise en charge thérapeutique (médicale ou chirurgicale) et de déterminer la cause de ces délais.RésultatsLe délai médian entre la première imagerie pathologique et le traitement est de 9,6 semaines. Les délais étaient significativement plus courts dans les stades tardifs et les carcinomes à petites cellules (p=0,001). Il existait une tendance à des délais plus courts pour les femmes et des délais plus longs pour les classes d’âge les plus élevées.ConclusionL’évaluation des délais de prise en charge, en particulier pour les stades précoces, s’intègre dans le contrôle de la qualité de prise en charge de ces pathologies.SummaryIntroductionLung cancer is the main cause of cancer death in France. The diagnosis is often late and the delay between the onset of symptoms and management is considered an aggravating factor.Material and methodsOur prospective study collected the dates of the start of management of 139 consecutive patients receiving first line treatment for thoracic cancer in our hospital between November 2008 and May 2009. The aim of this study was to evaluate the delays in medical or surgical treatments in patients with thoracic cancer and to determine the cause of these delays.ResultsThe median delay between the first abnormal chest X-ray and treatment was 9.6 weeks. The delays were significantly shorter in the late stages and in small cell cancer (P=0.001). There was a tendency for shorter delays in women and for longer delays in older patients.ConclusionEvaluation of the delays in treatment, particularly in the early stages, is part of the quality control of management of these diseases

The role of SRC-3 in estrogen-dependent vasoprotection during vascular wall remodeling postinjury

Estrogen receptors are hormone-inducible transcription factors requiring coactivators such as members of the SRC/p160 family to modulate the transcription of their target genes. This perspective will examine the interplay between estrogen receptors and their coactivators in vasoprotection during vascular wall remodeling

Mouse mammary tumor virus-like gene sequences are present in lung patient specimens

<p>Abstract</p> <p>Background</p> <p>Previous studies have reported on the presence of Murine Mammary Tumor Virus (MMTV)-like gene sequences in human cancer tissue specimens. Here, we search for MMTV-like gene sequences in lung diseases including carcinomas specimens from a Mexican population. This study was based on our previous study reporting that the INER51 lung cancer cell line, from a pleural effusion of a Mexican patient, contains MMTV-like <it>env </it>gene sequences.</p> <p>Results</p> <p>The MMTV-like <it>env </it>gene sequences have been detected in three out of 18 specimens studied, by PCR using a specific set of MMTV-like primers. The three identified MMTV-like gene sequences, which were assigned as INER6, HZ101, and HZ14, were 99%, 98%, and 97% homologous, respectively, as compared to GenBank sequence accession number <ext-link ext-link-id="AY161347" ext-link-type="gen">AY161347</ext-link>. The INER6 and HZ-101 samples were isolated from lung cancer specimens, and the HZ-14 was isolated from an acute inflammatory lung infiltrate sample. Two of the <it>env </it>sequences exhibited disruption of the reading frame due to mutations.</p> <p>Conclusion</p> <p>In summary, we identified the presence of MMTV-like gene sequences in 2 out of 11 (18%) of the lung carcinomas and 1 out of 7 (14%) of acute inflamatory lung infiltrate specimens studied of a Mexican Population.</p

Hypoxia Induces VEGF-C Expression in Metastatic Tumor Cells via a HIF-1 α-Independent Translation-Mediated Mechanism.

Various tumors metastasize via lymph vessels and lymph nodes to distant organs. Even though tumors are hypoxic, the mechanisms of how hypoxia regulates lymphangiogenesis remain poorly characterized. Here, we show that hypoxia reduced vascular endothelial growth factor C (VEGF-C) transcription and cap-dependent translation via the upregulation of hypophosphorylated 4E-binding protein 1 (4E-BP1). However, initiation of VEGF-C translation was induced by hypoxia through an internal ribosome entry site (IRES)-dependent mechanism. IRES-dependent VEGF-C translation was independent of hypoxia-inducible factor 1α (HIF-1α) signaling. Notably, the VEGF-C IRES activity was higher in metastasizing tumor cells in lymph nodes than in primary tumors, most likely because lymph vessels in these lymph nodes were severely hypoxic. Overall, this transcription-independent but translation-dependent upregulation of VEGF-C in hypoxia stimulates lymphangiogenesis in tumors and lymph nodes and may contribute to lymphatic metastasis

Detection of oncogenic virus genomes and gene products in lung carcinoma

We investigated a series of 122 cases of small cell lung carcinomas and non-small cell lung carcinomas for the presence of several viruses that are known to be oncogenic in humans. Thus, viral genomes (DNA) and/or RNA transcripts and/or proteins of human papillomaviruses (HPV) 16, 18, 31, 33, 51, Epstein–Barr virus (EBV), human herpesvirus 8 (HHV-8), human cytomegalovirus (HCMV) and simian virus 40 (SV40) were investigated on tissue sections (prepared in tissue microarrays) with different techniques of immunohistochemistry and in situ hybridisation. None of the cases displayed a single positive tumour cell for all the viruses tested whatever the technique applied. Of note, in five cases of tumours with lymphoid infiltrates, we detected scattered EBV (EBER)-positive bystander lymphocytes. In three cases, a faint nuclear staining was found with the anti-latent nuclear antigen/LANA1 (HHV-8) antibody. These cases were checked by PCR with two sets of primers (orf 26 and orf 75) and remained negative for this latter virus. Taken together, our data strongly suggest that the conventional human oncogenic viruses (HPV, EBV, HCMV, HHV-8 and SV40) are unlikely to play some role in the development of lung carcinomas

A subset of epithelioid and spindle cell rhabdomyosarcomas is associated with TFCP2 fusions and common ALK upregulation

Rhabdomyosarcomas with TFCP2 fusions represent an emerging subtype of tumors, initially discovered by RNA-sequencing. We report herein the clinicopathological, transcriptional, and genomic features of a series of 14 cases. Cases were retrospectively and prospectively recruited and studied by immunohistochemistry (MYF4, MYOD1, S100, AE1/E3, ALK), fluorescence in situ hybridization with TFCP2 break-apart probe (n = 10/14), array-comparative genomic hybridization (Agilent), whole RNA-sequencing (Truseq Exome, Illumina), or anchored multiplex PCR-based targeted next-generation sequencing (Archer (R) FusionPlex (R) Sarcoma kit). Patient's age ranged between 11 and 86 years, including 5 pediatric cases. Tumors were located in the bone (n = 12/14) and soft tissue (n = 2/14). Most bone tumors invaded surrounding soft tissue. Craniofacial bones were over-represented (n = 8/12). Median survival was 8 months and five patients are currently alive with a median follow-up of 20 months. Most tumors displayed a mixed spindle cell and epithelioid pattern with frequent vesicular nuclei. All tumors expressed keratins and showed a rhabdomyogenic phenotype (defined as expression of MYF4 and/or MYOD1). ALK was overexpressed in all but three cases without underlying ALK fusion on break-apart FISH (n = 5) nor next-generation sequencing (n = 14). ALK upregulation was frequently associated with an internal deletion at genomic level. TFCP2 was fused in 5 ' either to EWSR1 (n = 6) or FUS (n = 8). EWSR1 was involved in both soft tissue cases. FISH with TFCP2 break-apart probe was positive in all tested cases (n = 8), including one case with unbalanced signal. On array-CGH, all tested tumors displayed complex genetic profiles with genomic indexes ranging from 13 to 107.55 and recurrent CDKN2A deletions. FET-TFCP2 rhabdomyosarcomas clustered together and distinctly from other rhabdomyosarcomas subgroups. Altogether, our data confirm and expand the spectrum of the new family of FET-TFCP2 rhabdomyosarcomas, which are associated with a predilection for the craniofacial bones, an aggressive course, and recurrent pathological features. Their association with ALK overexpression might represent a therapeutic vulnerability.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas