Six years survival on imatinib with no disease progression after diagnosis of metastatic duodenal gastrointestinal stromal tumour: a case report

Introduction: A duodenal Gastrointestinal Stromal Tumour (GIST) is a rare finding and until recently advanced disease had a poor prognosis. A PubMed search revealed no reports of more than five years survival of inoperable GIST on chemotherapy with WHO performance status zero. Case Presentation: A 68 year old female was diagnosed with unresectable GIST in the duodenum with metastasis to liver, pancreas and omentum in November 2001. She was commenced on imatinib mesylate (Glivec) chemotherapy. This case report was prepared from the medical records and radiology reports. She had good tolerance with stable disease. After six years her CT scan showed no disease progression and her WHO performance status was zero. Conclusion: This report supports the view that imatinib is a safe and effective drug in controlling disease progression in advanced metastatic GIST and plays an important role in improving the patient's quality of life

Epidermal growth factor receptor (EGFR) downstream signalling pathway in primary colorectal tumours and related metastatic sites: optimising EGFR-targeted treatment options

We analysed the expression of activated (phosphorylated) Akt and MAPK in 98 cases of paired primary colorectal tumours and metastases with the aim to define better the epidermal growth factor receptor (EGFR)-related molecular profile of colorectal cancer as a tool for treatment selection. Among 47 (48%) EGFR-negative primary tumours, 35 cases (74%) were positive for phosphorylated Akt and MAPK. Among 51 (52%) EGFR-positive primary colorectal cancers, 13 (25%) cases were negative for phosphorylated Akt and 15 (29%) were negative for phosphorylated MAPK. In EGFR-negative metastases (56 cases, 55%), phosphorylated Akt was expressed in 41 (73%) and phosphorylated MAPK was expressed in 36 (64%) samples, whereas in EGFR-positive metastases, phosphorylated Akt and MAPK were negative in 14 (31%) and in 10 (22%) cases, respectively. Phosphorylated Akt expression in primary colorectal tumours changed from positive to negative in 16 (16%) paired metastases and from negative to positive in 13 (13%) related metastatic sites. Phosphorylated MAPK expression in primary tumours changed from positive to negative in 13 (13%) paired metastases and from negative to positive in 12 (12%) related metastatic sites. Our findings suggest that phosphorylated Akt and MAPK status in primary tumours does not correlate with Akt and MAPK status in corresponding metastases. EGFR downstream signalling pathway can be overactivated even in the absence of EGFR expression in a considerable proportion of patients

Occurence of common dolphins (Delphinus delphis) in the Gulf of Trieste and the northern Adriatic Sea

1. The Mediterranean common dolphin (Delphinus delphis), considered to have been very common in the past, had undergone a dramatic decline across most of the basin by the end of 1970s. In the northern Adriatic Sea, one of the regions with most available historical information, the common dolphin is thought to have been the most common and abundant cetacean throughout most of the 20th century. However, by the end of 1970s, it had virtually disappeared from the region and is now considered generally absent from the entire Adriatic Sea. 2. This contribution summarizes the occurrence of common dolphins in the Gulf of Trieste and provides a brief review of published records in other parts of the Adriatic Sea. 3. Systematic boat surveys in the wider area of the Gulf of Trieste between 2002 and 2019 confirmed that the common bottlenose dolphin (Tursiops truncatus) is the only regularly occurring cetacean species in this area. Despite this, several records of common dolphins were documented in the Gulf of Trieste between 2009 and 2012, through sightings of live animals or recovery of dead stranded animals. 4. Dorsal fin markings allowed the photo‐identification of some of these, suggesting that at least four different live individuals (three adults and one calf) occurred here in recent times. Most cases involved single adult individuals, but one included a mother‐calf pair that was temporarily resident in a port for several months, a behaviour atypical for this species. Photo‐identification showed that the presumed mother had previously been sighted in the Ionian Sea in Greece, over 1,000 km from the Gulf of Trieste, making this the longest documented movement for this species worldwide. 5. At present, the common dolphin continues to be rare in the region.Publisher PDFPeer reviewe

Evidence for distinct coastal and offshore communities of bottlenose dolphins in the north east Atlantic.

Bottlenose dolphin stock structure in the northeast Atlantic remains poorly understood. However, fine scale photo-id data have shown that populations can comprise multiple overlapping social communities. These social communities form structural elements of bottlenose dolphin (Tursiops truncatus) [corrected] populations, reflecting specific ecological and behavioural adaptations to local habitats. We investigated the social structure of bottlenose dolphins in the waters of northwest Ireland and present evidence for distinct inshore and offshore social communities. Individuals of the inshore community had a coastal distribution restricted to waters within 3 km from shore. These animals exhibited a cohesive, fission-fusion social organisation, with repeated resightings within the research area, within a larger coastal home range. The offshore community comprised one or more distinct groups, found significantly further offshore (>4 km) than the inshore animals. In addition, dorsal fin scarring patterns differed significantly between inshore and offshore communities with individuals of the offshore community having more distinctly marked dorsal fins. Specifically, almost half of the individuals in the offshore community (48%) had characteristic stereotyped damage to the tip of the dorsal fin, rarely recorded in the inshore community (7%). We propose that this characteristic is likely due to interactions with pelagic fisheries. Social segregation and scarring differences found here indicate that the distinct communities are likely to be spatially and behaviourally segregated. Together with recent genetic evidence of distinct offshore and coastal population structures, this provides evidence for bottlenose dolphin inshore/offshore community differentiation in the northeast Atlantic. We recommend that social communities should be considered as fundamental units for the management and conservation of bottlenose dolphins and their habitat specialisations

Cancer stem cell gene profile as predictor of relapse in high risk stage II and stage III, radically resected colon cancer patients.

Clinical data indicate that prognostic stratification of radically resected colorectal cancer based on disease stage only may not be always be adequate. Preclinical findings suggest that cancer stem cells may influence the biological behaviour of colorectal cancer independently from stage: objective of the study was to assess whether a panel of stemness markers were correlated with clinical outcome in resected stage II and III colon cancer patients. A panel of 66 markers of stemness were analysed and thus patients were divided into two groups (A and B) with most patients clustering in a manner consistent with different time to relapse by using a statistical algorithm. A total of 62 patients were analysed. Thirty-six (58%) relapsed during the follow-up period (range 1.63-86.5 months). Twelve (19%) and 50 (81%) patients were allocated into group A and B, respectively. A significantly different median relapse-free survival was observed between the 2 groups (22.18 vs 42.85 months, p=0.0296). Among of all genes tested, those with the higher "weight" in determining different prognosis were CD44, ALCAM, DTX2, HSPA9, CCNA2, PDX1, MYST1, COL1A1 and ABCG2. This analysis supports the idea that, other than stage, biological variables, such as expression levels of colon cancer stem cell genes, may be relevant in determining an increased risk of relapse in resected colorectal cancer patient

Role of vascular endothelial growth factor (VEGF) and VEGF-R genotyping in guiding the metastatic process in pT4a resected gastric cancer patients.

In radically resected gastric cancer the possibility to predict the site of relapse could be clinically relevant for the selection of post-surgical management. We previously showed that specific tumour integrins genotypes are independently associated with either peritoneal or hematogenous metastases (ITGA and ITGV). Recently VEGF and VEGF-R polymorphisms have been demonstrated to potentially affect tumour angiogenesis and the metastatic process in gastric cancer. We then investigated the role of VEGFs and VEGF-R genotyping in determining either peritoneal carcinosis or hematogenous metastases in radically resected gastric cancer patients. Tumour genotyping for integrins (ITGA and ITGV) was also performed according to our previous findings. Genotyping for VEGF-A, VEGF-C, VEGFR-1,2,3 and ITGA and ITGV was carried out on pT4a radically resected gastric tumours recurring with either peritoneal-only carcinosis or hematogenous metastases. 101 patients fulfilled the inclusion criteria: 57 with peritoneal carcinomatosis only and 44 with hematogenous spread only. At multivariate analysis, intestinal histology and the AC genotype of rs699947 (VEGFA) showed to independently correlate with hematogenous metastases (p = 0.0008 and 0.008 respectively), whereas diffuse histology and the AA genotype of rs2269772 (ITGA) independently correlated with peritoneal-only diffusion (p = <0.0001 and 0.03 respectively). Our results seem to indicate that combining information from genotyping of rs699947 (VEGFA, AC), rs2269772 (ITGA, AA) and tumour histology could allow clinicians to individuate gastric cancer at high risk for recurrence either with peritoneal or hematogenous metastases. The selection tool deriving from this analysis may allow an optimal use of the available treatment strategies in these patients

Effects of vessel traffic on relative abundance and behaviour of cetaceans : the case of the bottlenose dolphins in the Archipelago de La Maddalena, north-western Mediterranean sea

Acknowledgements This study was part of the Tursiops Project of the Dolphin Research Centre of Caprera, La Maddalena. Financial and logistical support was provided by the Centro Turistico Studentesco (CTS) and by the National Park of the Archipelago de La Maddalena. We thank the Natural Reserve of Bocche di Bonifacio for the support provided during data collection. The authors thank the numerous volunteers of the Caprera Dolphin Research Centre and especially Marco Ferraro, Mirko Ugo, Angela Pira and Maurizio Piras whose assistance during field observation and skills as a boat driver were invaluable.Peer reviewedPostprin

Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival.

Cardiac stem cells and early committed cells (CSCs-ECCs) express c-Met and insulin-like growth factor-1 (IGF-1) receptors and synthesize and secrete the corresponding ligands, hepatocyte growth factor (HGF) and IGF-1. HGF mobilizes CSCs-ECCs and IGF-1 promotes their survival and proliferation. Therefore, HGF and IGF-1 were injected in the hearts of infarcted mice to favor, respectively, the translocation of CSCs-ECCs from the surrounding myocardium to the dead tissue and the viability and growth of these cells within the damaged area. To facilitate migration and homing of CSCs-ECCs to the infarct, a growth factor gradient was introduced between the site of storage of primitive cells in the atria and the region bordering the infarct. The newly-formed myocardium contained arterioles, capillaries, and functionally competent myocytes that with time increased in size, improving ventricular performance at healing and long thereafter. The volume of regenerated myocytes was 2200 m3 at 16 days after treatment and reached 5100 m3 at 4 months. In this interval, nearly 20% of myocytes reached the adult phenotype, varying in size from 10 000 to 20 000 m3. Moreover, there were 4313 arterioles and 15548 capillaries/mm2 myocardium at 16 days, and 316 arterioles and 39056 capillaries at 4 months. Myocardial regeneration induced increased survival and rescued animals with infarcts that were up to 86% of the ventricle, which are commonly fatal. In conclusion, the heart has an endogenous reserve of CSCs-ECCs that can be activated to reconstitute dead myocardium and recover cardiac function