Structural,Electrical and Optical Properties of Pyrrolo[1,2-i][1,7] Phenanthroline-Based Organic Semiconductors

This work reports a study on structural, electrical and optical properties of some recently synthesized pyrrolo[1,2-i][1,7] phenanthrolines derivatives in thin films. The thin films were deposited onto glass substrates by spin coating technique, using chloroform as solvent. The obtained films exhibited a polycrystalline structure with an n–type semiconductor behavior after heat treatment in the temperature range 293–543 K, specific to each sample. The thermal activation energy lies between 0.68 and 0.78 eV, while the direct optical band gap values were found in the range 4.17–4.24 eV. The electrical and optical properties of the investigated organic semiconductor films were discussed in relation to microstructural properties, determined by the molecular structure. The investigated organic compounds are promising for applications in organic optoelectronics and nanoelectronics.     

Routine follow-up by magnetic resonance imaging does not improve detection of resectable local recurrences from colorectal cancer

OBJECTIVE: To determine if routine follow-up by magnetic resonance imaging (MRI) improves the detection of resectable local recurrences from colorectal cancer. SUMMARY BACKGROUND DATA: Surgical treatment offers the best prospect of survival for patients with recurrent colorectal cancer. Unfortunately, most cases are often diagnosed at an unresectable stage when traditional follow-up methods are used. The impact of MRI surveillance on the early diagnosis of local recurrences has yet to be ascertained. METHODS: Patients who underwent curative surgery for rectal and left-sided colon tumors were included in a program of pelvic surveillance by routine MRI, in addition to the standard follow-up protocol. Cases were then analyzed for mode of diagnosis, resectability, and overall survival. RESULTS: Pelvic recurrence was found in 30 (13%) of the 226 patients studied. MRI detected 26 of 30 (87%) and missed 4 of 30 (13%) cases with local recurrence. Of the latter, 3 were anastomotic recurrences. In 28 (14%) patients, local recurrence was suspected by an initial MR scan but cleared by subsequent MRI or CT-guided biopsy. Recurrent pelvic cancer was diagnosed by MRI with 87% sensitivity and 86% specificity. In 19 (63%) cases, CEA was abnormally elevated, and 9 patients (30%) were symptomatic. Surgical resection was possible in only 6 patients (20%). There was no difference between MRI and conventional follow-up tests in their ability to detect cases suitable for surgery. CONCLUSIONS: Pelvic surveillance by MRI is not justified as part of the routine follow-up after a curative resection for colorectal cancer and should be reserved for selectively imaging patients with clinical, colonoscopic, and/or biochemical suspicion of recurrent disease.     

Screening for functional tumor suppressor activity in pancreatic cancer

Pancreatic cancer has a well-known reputation as one of the leading causes of cancer deaths worldwide. Thus, acquisition of efficient approaches and markers for accurate detection at the earlier stages of the disease should be prioritized. We have been focusing on tumor suppressor genes (TSGs) activity in pancreatic cancer to find effective methods for its genetic diagnosis and/or treatment. In this study, we utilized the technique of micro-cell-mediated chromosome transfer (MMCT) to introduce a normal copy of human chromosome 18 individually into some pancreatic cancer cells. Subsequently, the tumorigenic ability of the resulting hybrids was assessed in vitro and in vivo. In vitro growth of the hybrid clones was significantly delayed as compared to the parental cells. This was paralleled by the hybrid cells promotion of invasive carcinomas in nude mice at a significantly lower rate and with a longer latency than the parental tumor cells. This study provides evidence that MMCT is an efficient tool for screening of tumor suppressor activity in pancreatic cancer. The functional data emerging from this study bring into sharp relief the implication of chromosome 18 as a putative location for new TSG(s), yet to be identified in this region.     

Chromosome 12, frequently deleted in human pancreatic cancer, may encode a tumor-suppressor gene that suppresses angiogenesis

Several lines of evidence have suggested that the long arm of chromosome 12 may carry a tumor-suppressor gene(s) that plays a role in pancreatic ductal carcinogenesis. We have previously found a significant association between loss of heterozygosity of the 12q arm and a poor prognosis in pancreatic cancer patients. In this study, we introduced a normal copy of chromosome 12 into some pancreatic ductal carcinoma cells. Both anchorage-dependent and -independent proliferations as well as invasiveness were similar throughout the hybrid clones when compared with their corresponding parental cells. In sharp contrast, significant suppression of tumorigenesis was observed after inoculation of the hybrid clones into nude mice. Measurements made up to 1 month later showed that there was a significant delay in the growth of tumors into which the introduced normal copy of chromosome 12 had been restored. More significantly, using our dorsal skin chamber and an intravital microscopy system experiment in SCID mice, we demonstrated and visualized directly that implantation of the hybrids failed to promote the angiogenic phenotype encountered in the parental cells. Gene expression profiling using the complementary DNA microarray system identified a set of 24 genes differentially expressed between the hybrids and parental cells. An additional set of 18 genes was also identified that were differentially expressed between the hybrid clone that lost its growth-suppression activity and one that retained such activity. Another set of 25 genes mapped on 12q was detected that showed high expression levels in the hybrid clones retaining growth-suppressive activity. In summary, this study provides the first functional evidence of the existence of an additional tumor-suppressor gene(s) on chromosome 12, whose absence is responsible for the pathogenesis in pancreatic ductal carcinogenesis.     

The role of chromosome 18 abnormalities in the progression of pancreatic adenocarcinoma

To date, the events that mediate tumor progression in pancreatic cancer are still poorly understood. Cytogenetic, allelotype, and somatic cell hybrid studies in human pancreatic adenocarcinoma have suggested that chromosome 18 may carry tumor suppressor genes (TSGs), including SMAD4. We previously identified that LOH of 18q at the SMAD4 locus, along with LOHs on 17p and 12q, positively associated with poor prognoses of pancreatic cancer patients. However, restoration of the SMAD4 gene did not suppress in vitro proliferation of pancreatic cancer cells that harbored homozygous deletion of this gene. An intraductal papillary mucinous neoplasm (IPMN ) is thought to be one of the premalignant lesions of the pancreas that progresses to carcinoma. Although there were frequent LOH (7/14, 50%) at the SMAD4 locus in IPMN samples, SMAD4 protein was observed immunohistochemically in tumor cells, and no mutations of the SMAD4 gene were observed, suggesting that it is the existence of a TSG in 18q, other than SMAD4, that suppresses cell growth. To functionally assess the activity of chromosome 18 in pancreatic cancer, we transferred a normal copy of the chromosome into pancreatic ductal carcinoma cells with and without completely inactivated SMAD4. In this study, in vitro growth of the hybrid cells was significantly suppressed compared with the parental cells, regardless of the initial SMAD4 status. To estimate the metastatic ability of the hybrids, we used a lung colonization model. At the end of the experiment, there was significant suppression of the number of surface metastases developing in mice injected with hybrids in comparison with those injected with parental cells. To identify and characterize genes that are involved in the progression of pancreatic cancer, we used micro-array expression analysis employing a 20k oligo-array system. It was revealed that there was increased expression of 4 genes relating to apoptosis in the 18 chromosome hybrids cells compared with the parental cells. We are now analyzing the function of these genes.     

Assessment of Strains Produced by Thermal Expansion in Printed Circuit Boards

The paper proposed an alternative optical metrology to classical methods (strain gauge measurements and numerical simulation) for strain determination on printed circuit board (PCBs) due to thermal loads. The digital image correlation (DIC) technique was employed to record the strain distribution in some particular areas of the PCB. A thermal load was applied using a heating chamber, and the measurements were performed at four different temperature steps (25 °C, 50 °C, 85 °C and 120 °C). An increase in the principal strains with temperature was observed. For validation, the principal strains on the PCB obtained with DIC were compared with the values from gauge strain measurements and numerical simulation. The conclusions highlighted that DIC represents a technique with potential for strain measurement caused by thermal deformation, with the advantages of full field measurement, less preparation of the surface and good accuracy.     

Diverse factors are involved in maintaining X chromosome inactivation

X chromosome inactivation (XCI) is the most dramatic example of epigenetic silencing in eukaryotes. Once established, the inactivated X chromosome (Xi) remains silenced throughout subsequent cell divisions. Though the initiation of XCI has been studied extensively, the protein factors involved in Xi silencing and maintenance are largely unknown. Here we report the discovery of a diverse set of 32 proteins involved in maintenance of Xi silencing through a genome-wide RNAi screen. In addition, we describe the mechanistic roles of two proteins--origin recognition complex 2 (Orc2) and heterochromatin protein 1 (HP1α)--in Xi silencing. Immunofluorescence studies indicate that Orc2 and HP1α localize on Xi in mouse cells. Depletion of Orc2 by shRNA leads to the loss of both Orc2 and HP1α localization on Xi. Furthermore, the silencing of genes on Xi is disrupted in both Orc2- and HP1α-depleted cells. Finally, we show, using ChIP assay, that the localization of HP1α and Orc2 to the promoter regions of Xi-silenced genes is interdependent. These findings reveal a diverse set of proteins involved in Xi silencing, show how Orc2 and HP1α impact Xi silencing, and provide a basis for future studies on the maintenance of Xi silencing.     

Warfarin-induced limb gangrene in the setting of lung adenocarcinoma

A 53-year-old man with lung adenocarcinoma developed pulmonary embolism and bilateral popliteal venous thrombosis. Treated with intravenous unfractionated heparin and discharged home on warfarin, he returned a week later with extending thrombosis. Treatment with heparin followed by warfarin was reinitiated. Twenty-four hours following the re-administration of warfarin, the patient's INR increased to 14.5. The platelet count dropped by more than 50%, and he developed venous limb gangrene of the left leg and skin necrosis of the right leg. Heparin-induced thrombocytopenia was ruled out, and coagulation studies showed a severe depletion of protein C as well as increased thrombin generation. The patient was transfused with fresh frozen plasma, and vitamin K was given. Heparin was continued, and after 4 weeks, the patient improved markedly showing only minimal necrosis of the toes. Venous limb gangrene is a major complication associated with warfarin therapy. Its pathogenesis is explained by a transient hypercoagulable state produced by protein C depletion that leads to microvascular thrombi progressing to venous limb gangrene. The present case emphasizes the importance of careful anticoagulation with heparin followed by slow initiation of low-dose warfarin, in order to minimize thrombotic complications.