Incongruity of Imaging Using Fluorescent 2-DG Conjugates Compared to 18F-FDG in Preclinical Cancer Models

Purpose

We compared the use of near-infrared conjugates of 2-deoxyglucose (NIR 2-DG) to 2-deoxy-2-[¹⁸F]fluoro-d-glucose (¹⁸F-FDG) for the purposes of imaging tumors, as well as response to therapy.

Procedures

Uptake of both ¹⁸F-FDG and NIR 2-DG within gastrointestinal stromal tumor xenografts were imaged before and after nilotinib treatment. Confocal microscopy was performed to determine NIR 2-DG distribution in tumors.

Results

Treatment with nilotinib resulted in a rapid reduction in ¹⁸F-FDG uptake and reduced tumor cell viability which was predictive of long-term antitumor efficacy. In contrast, optical imaging with NIR 2-DG probes was unable to differentiate control from niltonib-treated animals, and microscopic analysis revealed no change in probe distribution as a result of treatment.

Conclusions

These results suggest that conjugation of large bulky fluorophores to 2-DG disrupts the facilitated transport and retention of these probes in cells. Therefore, optical imaging of NIR 2-DG probes cannot substitute for ¹⁸F-FDG positron emission tomography imaging as a biomarker of tumor cell viability and metabolism.     

Seeking sex partners through the internet and mobile phone applications among men who have sex with men in Taiwan

It has become popular for men who have sex with men (MSM) to use mobile-phone geosocial networking applications (mobile apps) to find sex partners. A cross-sectional online survey was conducted in Taiwan to compare the sexual and substance-use behaviors of MSM seeking sex partners through the internet and mobile apps. Of the 1060 participants, 65.8% used the internet via computer and 37.7% used a mobile app to find sexual partners, while 30.3% used recreational drugs or alcohol in the previous 6 months. MSM who exclusively used mobile apps to seek sex partners were significantly more likely than MSM seeking sex via computer to be older, to have used recreational drugs or alcohol, and to have sex with HIV-positive partners. Additionally, using mobile apps to seek sex partners was significantly associated with having sex with online partners through either mobile apps or computer-based internet use (adjusted odds ratio (AOR), 7.12 [3.87–13.11]), self-reporting as HIV-positive (AOR, 2.24 [1.12–4.12]), using recreational drugs (AOR, 1.67 [1.21–2.32]), having disclosed HIV status to sexual partners (AOR, 1.44 [1.03–2.02]), and having sex with HIV-positive partners (AOR, 1.81 [1.06–3.10]). In conclusion, the mobile apps may serve as a feasible platform for HIV-positive MSM to find other HIV-positive partners.     

Rat C6 glial cells synthesize insulin-like growth factor I (IGF-I) and express IGF-I receptors and IGF-II/mannose 6-phosphate receptors

We have used the rat C6 glial cell line as a model system to study the role of insulin-like growth factors (IGF) in neuroglial cells of the central nervous system (CNS). Northern blot analysis of C6 RNA demonstrated the presence of IGF-I mRNA and undetectable IGF-II mRNA. IGF-I and IGF-binding protein(s), but not IGF-II, were detected in C6 glial cell-conditioned medium. The level of IGF-I was 1-4 ng/ml in conditioned medium based on a human IGF-I standard. The immunoreactive IGF-I inhibited [125I]IGF-I binding to the IGF-I receptor on chick embryo fibroblasts and stimulated [3H]thymidine incorporation into chick embryo fibroblast DNA. Competitive binding and affinity cross-linking experiments using [125]IGF-I and [125I]IGF-II demonstrated the presence of IGF-I receptors (type I) and IGF-II/mannose 6-phosphate receptors (type II) on C6 glial cell membranes. An immunoglobulin (no. 3637) directed against the rat IGF-II receptor blocked the degradation of [125I]IGF-II added to C6 glial cells, presumably by blocking receptor-mediated internalization. We were unable to demonstrate an autocrine role for IGF in the C6 glial cell line, since [3H]thymidine incorporation into DNA was stimulated equally well by IGF-I-deficient rat serum and normal serum, and added IGF did not stimulate [3H]thymidine incorporation into DNA when tested alone or when added to IGF-I-deficient serum. We propose that neuroglial cell-derived IGF-I may serve as a paracrine growth stimulus in the central nervous system.     

Electrophysiological determinant for induction of isthmus dependent counterclockwise and clockwise atrial flutter in humans

OBJECTIVE: To investigate the electrophysiological determinant underlying the electrical induction of counterclockwise and clockwise isthmus dependent atrial flutter. PATIENTS AND METHODS: The isthmus bordered by the inferior vena caval orifice-tricuspid annulus-coronary sinus ostium (IVCO-TA-CSO) has been assumed to be the site of both slow conduction and unidirectional block critical to the initiation of atrial flutter. Trans-isthmus and the global atrial conduction were studied in 25 patients with isthmus dependent atrial flutter (group A) and in 21 patients without atrial flutter (group B), by pacing at the coronary sinus ostium and the low lateral right atrium (LLRA) and mapping with a 20 pole Halo catheter in the right atrium. RESULTS: Mean (SD) fluoroscopic isthmus length between the coronary sinus ostium and LLRA sites was 28.1 (4.0) mm in group A and 28.0 (3.9) mm in group B (p = 0.95), but the trans-isthmus conduction velocity of both directions at various pacing cycle lengths was nearly halved in group A compared with group B (mean 0.39-0.46 m/s v 0.83-0.89 m/s, p < 0.0001). Pacing at coronary sinus ostium directly induced counterclockwise atrial flutter in 14 patients and pacing at LLRA induced clockwise atrial flutter in 11 patients, following abrupt unidirectional trans-isthmus block. Transient atrial tachyarrhythmias preceded the onset of atrial flutter in 10 counterclockwise and six clockwise cases of atrial flutter. None of the group B patients had inducible atrial flutter even in the presence of trans-isthmus block. The intra- and interatrial conduction times, as well as the conduction velocities at the right atrial free wall and the septum, were similar and largely within the normal range in both groups. CONCLUSIONS: Critical slowing of the trans-IVCO-TA-CSO isthmus conduction, but not the unidirectional block or the global atrial performance, is the electrophysiological determinant of the induction of counterclockwise and clockwise isthmus dependent atrial flutter in man.     

CIHR Canadian HIV Trials Network Co-Infection and Concurrent Diseases Core: Updated Canadian guidelines for the treatment of hepatitis C infection in HIV-hepatitis C coinfected adults

BACKGROUND:Hepatitis C virus (HCV) coinfection occurs in 20% to 30% of Canadians living with HIV and is responsible for a heavy burden of morbidity and mortality. Management of HIV-HCV coinfection is more complex due to the accelerated progression of liver disease, the timing and nature of antiretroviral and HCV therapy, mental health and addictions management, socioeconomic obstacles and drug-drug interactions between new HCV direct-acting antiviral therapies and antiretroviral regimens.OBJECTIVE:To update national standards for the management of HCV-HIV coinfected adults in the Canadian context.METHODS:A standing working group with specific clinical expertise in HIV-HCV coinfection was convened by The Canadian Institute of Health Research HIV Trials Network to review recently published data regarding HCV antiviral treatments and to update the Canadian HIV-HCV coinfection guidelines.RESULTS:Recent data suggest that the gap in sustained virological response rates between HCV monoinfection and HIV-HCV coinfection has been eliminated with newer HCV antiviral regimens. All HIV-HCV coinfected individuals should be assessed for HCV therapy. First-line treatment for genotypes 1 through 6 includes pegylated interferon and weight-based ribavirin dosing plus the nucleotide sofosbuvir for 12 weeks. Sofosbuvir in combination with the protease inhibitor simeprevir is another first-line consideration for genotype 1 infection. Sofosbuvir with ribavirin for 12 weeks (genotype 2) and 24 weeks (genotype 3) is also recommended as first-line treatment.DISCUSSION:Recommendations may not supersede individual clinical judgement.     

Role of tyrosine kinase activity in cardiac slow delayed rectifier channel modulation by cell swelling

 We studied the effects of cell swelling on membrane currents of canine ventricular myocytes using the whole-cell patch-clamp method. Cell swelling was induced by lowering the osmolarity of the bath solution to 60% of control. Cell width and currents were measured simultaneously. Cell swelling induced little or no change in the L-type Ca, the inward rectifier, and the transient outward currents, but a marked increase in the slow delayed rectifier current (I _Ks) was seen. We further examined the role of protein kinase activities in I _Ks modulation by cell swelling. This modulation was not affected by inhibiting serine/threonine kinases using H-8. On the other hand, the modulation was inhibited by genistein (a protein tyrosine kinase inhibitor) although not by daidzein (an inactive analogue of genistein). Our data suggest that in canine ventricle cell swelling can increase protein tyrosine kinase activity, which can augment I _Ks and contribute to changes in membrane electrical activity observed under these conditions. Received: 20 September 1996 / Received after revision and accepted: 5 December 1996     

Establishment and characterization of a rectal cancer model in mice: application to cytokine gene therapy

BACKGROUND AND AIMS: We established an orthotopic animal model of rectal cancer in mice and applied this model to the study of the antitumor effects of cytokine-assisted tumor vaccine. MATERIALS AND METHODS: The CT-26 murine colon adenocarcinoma cells were inoculated into the submucosa of the rectum of the mice to induce the rectal tumor. The tumor growth rate and the survival time of the mice were observed. The cDNA of granulocyte-macrophage colony-stimulating factor (GM-CSF) was transduced to the CT-26 cell line via a retroviral vector, and the therapeutic effects of irradiated GM-CSF secreting tumor vaccine on the rectal tumor were investigated. RESULTS: All the mice implanted with the wild-type tumor cells had tumor growth in the rectum and died. The mean survival time of the mice was 28.9 days. Two doses of irradiated GM-CSF secreting tumor vaccine administered on days 0 and 3 after tumor cell implantation significantly prolonged the survival of the mice with rectal tumor compared with that of the control groups ( P<0.0001). In contrast, no antitumor effect was observed when the treatment with GM-CSF secreting tumor vaccine was delayed to 3 days after tumor cell implantation ( P>0.17). CONCLUSION: The results suggest that cytokine gene therapy exerts an antitumor effect on small tumors and may be considered as an adjuvant immunotherapy of rectal cancers and prevention of reimplantation of tumor cells disseminated during or following surgery. The orthotopic animal model of the rectal cancer in mice could be applied to the in vivo experimental studies of rectal cancer.     

Co-existence of a huge pseudocyst and mucinous cystadenoma: report of a case and the value of magnetic resonance imaging for differential diagnosis

Co-existence of a pancreatic pseudocyst and a neoplastic cyst is rare and their differential diagnosis is difficult if the patient has an atypical history as well as subclinical symptoms. The formation of a pseudocyst under such circumstances is usually the result of downstream ductal obstruction by the neoplasm. Two large cysts were found in a 43-year-old woman who had symptoms of gastric outlet obstruction that were the result of external compression by one of the cysts. Magnetic resonance imaging was superior to computed tomography, discriminating between the internal contents and surrounding tissue of the two cysts, enabling the correct preoperative diagnosis of a pseudocyst co-existing with a mucinous cystadenoma to be made. It was most unusual for the pseudocyst to be located downstream of the mucinous tumour, ruling out ductal obstruction by the tumour in its pathogenesis. A possible explanation for the pseudocyst formation in this case was pancreatic juice accumulation in the space of the lesser sac after pancreatic parenchymal destruction by the mucinous tumour.