Management of concurrent colorectal cancer and vascular disease in the endovascular era.

UNLABELLED: Concurrent colorectal cancer (CRC) and vascular disease, such as abdominal aortic aneurysm, represents a challenging clinical situation. Both lesions may lead to the demise of the patient and therefore should be treated. Endovascular techniques may enhance decision-making and even permit single-stage treatment. PATIENTS AND METHODS: Retrospective review of patients in a university department with extensive endovascular experience. Between 2004 and 2010, seven patients with synchronous vascular disease and colorectal cancer were identified. RESULTS: The mean age was 73 years, and all patients were men. Five patients had concurrent CRC and aneurysmal disease. Two had synchronous critical carotid artery stenosis and CRC. All vascular lesions were treated with endovascular techniques. All CRC were resected with open techniques. In four patients, endovascular repair followed by staged CRC resection was performed. In three patients, single-stage procedures were performed. There was one perioperative death, for a mortality of 14.3% in our series. There were no graft infections. CONCLUSIONS: Priority of treating concurrent vascular disease and CRC remains a dilemma. Combined treatment with a single-stage procedure is feasible. Risk of graft infection may be lower than expected.

Endovascular repair of a spontaneous ilio-iliac fistula presenting as pulmonary embolism.

Spontaneous rupture of a common iliac artery aneurysm into the common iliac vein is a rare phenomenon. We report the case of a 68 year old man admitted with acute cardiac failure and massive pulmonary embolism as a complication of a spontaneous ilio-iliac fistula, secondary to aneurysmal rupture. The aneurysm was successfully excluded using an aorto-uni-iliac stent graft. No complications were noted at 9 months follow-up. Arteriovenous fistulae should be considered in patients with aortic or iliac aneurysms who develop a pulmonary embolism or symptoms of venous congestion. Endovascular repair of these pathologies is a feasible therapeutic option; however long term results remain unknown.

Midterm results of endovascular abdominal aortic aneurysm repair with Talent stent graft in a single center.

AIM: The aim of this study is to investigate the safety and efficacy of abdominal aortic aneurysm (AAA) repair with modular bifurcated Talent stent-graft. METHODS: Between September 2001 and September 2005, 85 patients with infrarenal AAA underwent treatment with Talent stent-graft. There were 83 men and 2 women with a median age of 69.3 years. Anatomy of the abdominal aorta and the iliac arteries was investigated with high resolution contrast CT together with digital subtraction angiography. The majority of patients had comorbid illnesses like arterial hypertension (60%), CAD (38%) and previous CABG (26%). Duration of follow-up period ranged from 1 to 48 months (median 18 months). RESULTS: Repair was performed with transrenal fixation of the bifurcated Talent stent-graft under regional anesthesia in 80% of all cases. Technical success rate was 97.6%. Aneurysm related mortality was 2.4% due to aneurysm rupture in the postoperative period. Overall mortality rate was 9.4%. Morbidity rate was 16.5%. Immediate conversion to open repair was necessary in 1 patient (1.2%). Endoleak rate was 4.8% at 1 month follow-up period. Secondary intervention was required in 1.2% of patients. Iliac limb occlusion was detected in 1 patient (1.2%). CONCLUSIONS: Talent stent-graft exhibits a high degree of technical success in AAA repair in patients with comorbid conditions with a low perioperative morbidity and mortality rate.

Priority of resection in concomitant abdominal aortic aneurysm (AAA) and colorectal cancer (CRC): review of the literature and experience of our clinic.

The concomitant occurrence of abdominal aortic aneurysm (AAA) and colorectal cancer (CRC), although rare, always represents a therapeutic dilemma. The incidence of coexistence ranges between 0.49 and 2.1%. Both lesions should be treated to achieve best life expectancy. But the main controversy revolves around whether to treat them simultaneously or as staged procedures. In our institution, we treated seven cases of concomitant AAA and CRC. In five of them, synchronous conventional resection was preferred. In the latest two, which we present, endovascular aortic repair was chosen. No graft infection was documented.

Aggregation of hsp70 and hsc70 in vivo is distinct and temperature-dependent and their chaperone function is directly related to non-aggregated forms.

We used non-denaturing gradient analysis of cell extracts before and after heat treatment of the cells and showed that hsp70 and hsc70 aggregate in vivo in a temperature-dependent fashion. Their aggregation profiles were found to be clearly distinguishable and sensitive to ATP depletion. Pore exclusion limit electrophoresis showed that these two proteins are mainly found in autoaggregated forms including dimers, trimers and oligomers. The addition of denatured luciferase to the cell extracts reversed the aggregation of both proteins towards their non-aggregated forms. Immunoprecipitation and Western-blot analysis showed that the non-aggregated form is the only one bound to denatured luciferase. Our results suggest that aggregated hsp70 and hsc70 represent predominantly self-associated molecules unable to exert chaperone activity. The cochaperone hsp40 was also found to be aggregated and, on addition of denatured luciferase, its aggregation was reversed to a non-aggregated state. Immunoprecipitation analysis indicated that hsp40 forms a complex with the non-aggregated form of hsc70 and denatured luciferase. These results confirm previous in vitro studies and support the suggestion that in vivo cytosolic hsp70 and hsc70 exist mainly in an oligomer-monomer equilibrium which is dependent on the environmental temperature, the levels of ATP and the presence of denatured proteins.

The hsc70 gene which is slightly induced by heat is the main virus inducible member of the hsp70 gene family.

We have found that SV40 infection of CV1 cells induces the synthesis of a 72 kDa protein that upon molecular cloning was shown to be the product of the hsc70 gene. The above gene product was found to be mainly virus inducible, in contrast to the hsp70 gene product which was mainly heat inducible. The two genes were found to be cell cycle regulated in a distinctively different manner.

Constitutive expression of heat-shock protein 70 in mammalian cells confers thermoresistance.

A 70-kDa heat-shock-protein (hsp 70) expression vector which contains the human hsp 70 gene linked to the human beta-actin promoter, was constructed and used to transfect CV1 monkey cells. Stably transfected CV1 clones were isolated which constitutively synthesized increased amounts of hsp70 at normal temperature. It is shown that these clones are resistant to elevated temperature. This finding indicates that hsp70 is involved in the protection of the cells against a lethal heat treatment and maybe responsible for the phenomenon of thermotolerance.

Nuclear lamina heterogeneity in mammalian cells. Differential expression of the major lamins and variations in lamin B phosphorylation.

We have studied the molecular composition of the nuclear lamina in rat tissues of distinct embryological origin and the occurrence of the nuclear lamins during in vitro differentiation of the mouse F9 teratocarcinoma cell line. Immunochemical analysis demonstrated that all rat tissues contained the three major lamin forms (lamins A, B, and C) previously recognized in rat liver nuclei; however, other minor cross-reactive components were also identified in some tissues. The amount of the 67-kDa lamin B complexed with lamins A and C in the laminae of different tissues ranged from a stoichiometry of much less than 1 to approximately 1. Furthermore, it was found that F9 stem cells and their differentiated progeny express only lamin B, and Northern blotting analysis indicated that these cells fail to accumulate lamin A and C mRNA. Chemical cleavages and peptide mapping suggested that the 67-kDa lamin B form was of similar primary structure in all differentiated tissues and F9 cells. Employing antibodies with different affinities for phosphorylated and nonphosphorylated lamin B, we showed that the apparent invariance in the expression of this polypeptide is overriden by a heterogeneity produced via tissue-specific phosphorylation. Because similar differences in antibody recognition could be reproduced in vitro by phosphorylating lamin B with protein kinase A, we have concluded that the tissue-specific modifications of this protein may occur at consensus sites recognized by this enzyme. These data support the hypotheses that the lamins can form functional laminae by associating at various combinations, and that processes including differential lamin synthesis and post-translational modification can produce a steady state lamina heterogeneity.

Role of the adenovirus 72-kDa DNA binding protein in the rapid decay of early viral mRNA.

Previous experiments have shown that the early adenovirus E1A and E1B mRNAs decay with a half-life of 20 min in a lytic infection dependent on the action of the viral 72-kDa DNA binding protein. In contrast, the same E1A and E1B mRNAs are stable when synthesized in 293 cells, an adenovirus-transformed cell line that is devoid of the 72-kDa protein. If 293 cells are infected with the E1A deletion mutant dl312, the endogenous E1A RNA disappears after 4 hr of infection, a time coincident with the appearance of the 72-kDa protein. The induction of decay is specific since there is no decrease in the level of actin or certain other cellular mRNAs. Thus, the stability of the early RNAs is variable and correlates with the presence of the 72-kDa protein. An interaction of the 72-kDa DNA binding protein with RNA inside the cell has been demonstrated by in vivo crosslinking of protein to RNA. However, the protein is found in association with actin mRNA as well as E1A mRNA. Thus, although the 72-kDa protein appears to be required for the rapid decay of viral mRNA it apparently does not impart specificity to the process.

Specific inhibition of simian virus 40 protein synthesis by heat and arsenite treatment.

The effects of heat treatment of CV1 cells infected with simian virus 40 (SV40) on viral and cellular protein synthesis were investigated by one-dimensional and two-dimensional polyacrylamide gel electrophoresis. A 12-h heat treatment during the late phase of the viral life-cycle inhibits VP1 synthesis. No inhibition of normal cellular proteins is apparent, but heat-shock proteins are strongly induced and accumulate in the cells. Inhibition of VP1 synthesis in infected cells is demonstrated to occur also after arsenite treatment, another agent known to induce heat-shock proteins. Northern blot analysis of cytoplasmic RNA demonstrated a decrease in the abundance of late SV40 mRNAs thus showing that the inhibition occurs at the transcriptional or immediately post-transcriptional level. Cumulative labeling with [3H]thymidine of viral DNA showed that the decrease in the abundance of late mRNAs is not due to a blocking of viral DNA synthesis. Immunofluorescence microscopy and immunoprecipitation analysis show that heat and arsenite treatments also affect the synthesis of T antigen. These results suggest that heat-shock proteins may play a role in the inhibition of SV40 virus gene functions.

Genes for skeletal muscle myosin heavy chains are clustered and are not located on the same mouse chromosome as a cardiac myosin heavy chain gene.

Myosin heavy chain (MHC) genes are expressed as several distinct isoforms in a tissue- and stage-specific manner; three skeletal muscle MHC isoforms appear sequentially during development. We have isolated cDNA clones, identified by RNA blot hybridization and by nucleotide sequence determination as coding for portions of the embryonic (pMHC2.2), perinatal (pMHC16.2A), and alpha(V1) cardiac (pMHC141 and pMHC101) MHC isoforms. These four probes and the adult skeletal MHC probe (pMHC32) have been used on Southern blots of genomic DNA to detect restriction fragment length polymorphisms defining the alleles for these genes in mouse species Mus musculus and Mus spretus. In this way, we followed the segregation of skeletal and cardiac MHC genes in 42 offspring resulting from an interspecies backcross. We found that the embryonic, perinatal, and adult skeletal MHC genes are clustered on chromosome 11 near the locus nude, the skeletal and cardiac MHC genes do not cosegregate, and the alpha(V1) cardiac MHC gene is located on chromosome 14 close to Np-1. This result is in contrast to that for other contractile protein genes such as the alkali myosin light chain and the actin multigene families, which are dispersed in the genome.