Monocyte chemotaxis in bronchial carcinoma and cigarette smokers.

Chemotaxis of blood monocytes was measured in 31 patients with bronchial carcinoma and 19 cigarette smokers. Thirteen patients with metastatic bronchial carcinoma had significantly less (P less than 0.005) chemotactic response than matched controls. Those with disease confined to the chest, or with recurrent or operable bronchial carcinoma, had no significant depression of monocyte chemotaxis. There was also no significant difference in monocyte chemotaxis between cigarette smokers and matched controls. These results support the concept that in human cancer there is a defect in monocyte chemotaxis, but in bronchial carcinoma significant depression was only apparent in those with advanced disease

Albumin-heparin microspheres as carriers for cytostatic agents

Much work has been done on adriamycin-loaded albumin microspheres (Alb-MS) for chemoembolization [1–4], the rationale being that site-specific drug delivery may increase the therapeutic efficacy of the drug. Alb-Ms are being investigated because of their biocompatibility and because the degradation products of these microspheres are non-toxic. However, these microspheres have some disadvantages (i.e. drug loading during the microsphere preparation, low payloads, large burst effects). These disadvantages can be overcome by the incorporation of heparin (a highly negatively charged mucopolysaccharide). Albumin-heparin microspheres were prepared (i) by crosslinking of soluble albumin and heparin first using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and subsequently glutaraldehyde (Alb-Hep-MS) and (ii) by crosslinking a preformed soluble conjugate of heparin and albumin with glutaraldehyde (Alb-Hep-Conj-MS). Albumin-heparin microspheres could be loaded with adriamycin after microsphere preparation giving payloads of 15–30%. Preliminary in vitro adriamycin release experiments showed that Alb-Hep-Conj-MS exhibit sustained release properties. Furthermore ion-exchange properties could be observed both with Alb-Hep-MS and Alb-Hep-Conj-MS. In vitro and in vivo toxicity experiments with Alb-Hep-MS showed no adverse effects

Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1

Considerable evidence implicates DISC1 as a susceptibility gene for multiple psychiatric diseases. DISC1 has been intensively studied at the molecular, cellular and behavioral level, but its role in regulating brain connectivity and brain network function remains unknown. Here, we utilize a set of complementary approaches to assess the functional brain network abnormalities present in mice expressing a truncated Disc1 gene (Disc1tr Hemi mice). Disc1tr Hemi mice exhibited hypometabolism in the prefrontal cortex (PFC) and reticular thalamus along with a reorganization of functional brain network connectivity that included compromised hippocampal–PFC connectivity. Altered hippocampal–PFC connectivity in Disc1tr Hemi mice was confirmed by electrophysiological analysis, with Disc1tr Hemi mice showing a reduced probability of presynaptic neurotransmitter release in the monosynaptic glutamatergic hippocampal CA1–PFC projection. Glutamate system dysfunction in Disc1tr Hemi mice was further supported by the attenuated cerebral metabolic response to the NMDA receptor (NMDAR) antagonist ketamine and decreased hippocampal expression of NMDAR subunits 2A and 2B in these animals. These data show that the Disc1 truncation in Disc1tr Hemi mice induces a range of translationally relevant endophenotypes underpinned by glutamate system dysfunction and altered brain connectivity

Phase II study of ACNU in non-small-cell lung cancer: EORTC study 08872

A total of 62 patients with metastatic or locally advanced non-small-cell lung cancer were entered in a phase II study of ACNU. Initially, the drug was given i. v. at a dose of 100 mg/m2 every 6 weeks, but due to observed haematological side effects in chemotherapy-pretreated patients, the dose was lowered in this group to 75 mg/m2. We observed one complete response in a subject exhibiting multiple lung metastases and a partial response in two patients, one showing brain metastases and one who experienced local disease recurrence. The toxicity of ACNU mainly consisted of bone marrow suppression especially thrombocytopenia, with one toxic death occurring due to intracerebral haemorrhage. We concluded that at this dose and on this schedule, ACNU has limited activity in non-small-cell lung cancer

Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1

Considerable evidence implicates DISC1 as a susceptibility gene for multiple psychiatric diseases. DISC1 has been intensively studied at the molecular, cellular and behavioral level, but its role in regulating brain connectivity and brain network function remains unknown. Here, we utilize a set of complementary approaches to assess the functional brain network abnormalities present in mice expressing a truncated Disc1 gene (Disc1tr Hemi mice). Disc1tr Hemi mice exhibited hypometabolism in the prefrontal cortex (PFC) and reticular thalamus along with a reorganization of functional brain network connectivity that included compromised hippocampal-PFC connectivity. Altered hippocampal-PFC connectivity in Disc1tr Hemi mice was confirmed by electrophysiological analysis, with Disc1tr Hemi mice showing a reduced probability of presynaptic neurotransmitter release in the monosynaptic glutamatergic hippocampal CA1-PFC projection. Glutamate system dysfunction in Disc1tr Hemi mice was further supported by the attenuated cerebral metabolic response to the NMDA receptor (NMDAR) antagonist ketamine and decreased hippocampal expression of NMDAR subunits 2A and 2B in these animals. These data show that the Disc1 truncation in Disc1tr Hemi mice induces a range of translationally relevant endophenotypes underpinned by glutamate system dysfunction and altered brain connectivity