Complete metabolic response in a patient with repeatedly relapsed non-small cell lung cancer harboring ROS1 gene rearrangement after treatment with crizotinib.

A 55-year-old Caucasian woman with lung adenocarcinoma stage IV presented with repeated relapse after treatment with cytotoxic chemotherapy (carboplatin, gemcitabine, docetaxel, pemetrexed) and targeted agents (erlotinib, cetuximab, sunitinib). Comprehensive molecular diagnostics (EGFR-, ALK-, RAS-, BRAF-, PIK3CA-, HER2- and DDR2-aberrations) were performed and failed initially to detect any driver mutation. While the patient suffered from rapid deterioration of her general condition, in particular from progressive dyspnea due to lung metastases, we implemented screening for RET- and ROS1 translocations into our molecular diagnostic program based on recent reports of these new molecular subgroups in lung adenocarcinoma. On retesting the patient's tumor sample was found to harbor a ROS1-translocation. The patient was subsequently treated with crizotinib and experienced a pronounced clinical improvement corresponding to a complete metabolic response in (18)F-FDG-PET and a good and confirmed partial response in CT (RECIST 1.1). Our case exemplifies the need for rapid implementation of newly discovered rare genetic lung cancer subtypes in routine molecular diagnostics.

Concurrent positive and negative goalbox events produce runway behaviors comparable to those of cocaine-reinforced rats.

Rats traversing a straight-alley for reinforcing stimuli typically exhibit faster running times as training proceeds. In previous work from this laboratory, animals running for a reinforcement consisting of intravenous infusions of cocaine, unexpectedly demonstrated a progressive increased time to enter the goalbox over trials. Closer observation revealed that the animals were exhibiting a unique retreat behavior (i.e., stopping their forward advance toward the goalbox and returning toward the startbox). It was hypothesized that the retreat behavior reflected an inherent conflict that originated from concurrent positive and negative associations with the goalbox. Such associations were attributed to cocaine's dual and well documented reinforcing and anxiogenic effects. To test this idea, the present study compared the runway behavior of animals that concurrently received food and mild foot shock in the goalbox to the behavior of the other animals running for cocaine. Results demonstrated that food + shock reinforced animals took longer to enter the goalbox and made more retreats than a control group that received only food in the goalbox. Both these effects were reversed by pretreatment with the anticonflict, anxiolytic drug, diazepam. The behavior pattern of animals that received the combination of food and footshock was found to strongly resemble that of IV cocaine-reinforced rats, a result consistent with the notion that chronic cocaine administration has both positive and negative consequences.

Effects of haloperidol in a response-reinstatement model of heroin relapse.

The present study employed an animal model of drug relapse in which previously extinguished heroin self-administration behavior was reinstated following a single reinforced trial. Male albino rats were trained to traverse a straight-alley for a reinforcer consisting of a single IV injection of 0.06 mg/kg diacetylmorphine (heroin). Once the alley-running had been established, the heroin reinforcer was removed and the operant behavior permitted to extinguish over trials. On treatment day, animals were injected 45 min prior to testing with 0.0, 0.075, 0.10, 0.15 or 0.3 mg/kg of the dopamine receptor antagonist, haloperidol. A single trial was then conducted during which some animals continued to experience extinction conditions while others were injected with the heroin reinforcer upon entry into the goal box. The effects of these manipulations were determined during an additional single test trial conducted 24 h later when the subjects were no longer drugged. While heroin produced a reliable reinstatement in operant responding, this effect was dose-dependently prevented by pretreatment with haloperidol. These data suggest that dopamine receptor antagonism alters the reinforcing consequences of heroin administration as measured by heroin's ability to reinstate operant behavior following a prolonged period of nonreinforced responding.

Qualitative and quantitative differences in the operant runway behavior of rats working for cocaine and heroin reinforcement.

Animals were trained to traverse a straight alley for drug reinforcement consisting of five IV injections of either 0.75 mg/kg/injection cocaine (n = 6) or 0.06 mg/kg/injection heroin (n = 6). Testing involved single daily trials during which the latency to leave the start box and the time required to traverse the alley were recorded for each animal. In addition, input from 12 pairs of infrared photocell detector/emittors placed along the length of the alley provided information on the precise location of the animal at 0.1-s intervals throughout the course of each trial. This information was recorded by computer and provided the basis for construction of graphic representations of each trial in the form of spatiotemporal records that revealed the precise route the subject took in getting to the goal box. The experiment revealed substantial differences in the runway behavior of heroin and cocaine animals. While the heroin group exhibited typical patterns of operant performance in that both start latency and goal times decreased gradually over the course of the experiment, cocaine animals were reliably slower than heroin subjects to leave the start box and exhibited a progressive increase in goal times over trials. The latter effect appeared to be a consequence of a "stop and retreat" behavior that was observed in all six cocaine subjects and increased in frequency as the experiment progressed. Because the runway behaviors exhibited here were emitted prior to delivery of the drug reinforcer, they suggest that the motivational state underlying drug-seeking behavior is qualitatively different for heroin- and cocaine-reinforced animals.

Animal model for investigating the anxiogenic effects of self-administered cocaine.

Male albino rats were trained to traverse a straight alley for a reward of five intravenous injections of cocaine (0.75 mg/kg/injection in a volume of 0.1 ml/injection delivered over 4 s). Animals were tested one trial per day with the following dependent measures assessed on each trial: start latency, running time, the number of retreats, and the location within the alley where each retreat occurred. While start latencies remained short and stable, running times tended to increase over days. This effect was apparently related to a concomitant increase in the number of retreats occurring in the alley (r = 0.896). Retreats tended to occur in very close proximity to the goal box, suggesting that animals working for IV cocaine come to exhibit a form of conflict behavior (i.e., retreats) putatively stemming from the drug's well documented rewarding and anxiogenic properties. Consistent with this hypothesis was the demonstration that diazepam (0.5, 1.0, 2.0 mg/kg IP) pretreatment dose-dependently reduced the incidence of retreat behaviors in the alley. In addition, the rewarding efficacy of the cocaine dosing parameters was subsequently confirmed in the runway subjects by conditioned place preference. The present paradigm, therefore, provides a useful method for investigating the anxiogenic effects of self-administered cocaine in laboratory animals.

Color vision in the dog.

The color vision of three domestic dogs was examined in a series of behavioral discrimination experiments. Measurements of increment-threshold spectral sensitivity functions and direct tests of color matching indicate that the dog retina contains two classes of cone photopigment. These two pigments are computed to have spectral peaks of about 429 nm and 555 nm. The results of the color vision tests are all consistent with the conclusion that dogs have dichromatic color vision.

Biological monitoring of environmental pollution and human exposure to some trace elements.

The extent of environmental pollution and resulting human exposure to hazardous toxic chemicals in the environment is often difficult to assess. One of the possible alternative approaches to this problem is the use of the biological indicators to demonstrate environmental pollution. This approach appears to be particularly suitable for demonstrating exposure to potentially toxic trace elements. In addition to analyses of plant and animal specimens the element content of human hair as an indicator of exposures to arsenic, mercury, cadmium, lead, antimony, manganese, nickel and cobalt has been repeatedly confirmed as reliable, provided the analyses were carried out and evaluated on group diagnostic basis and were done in groups of individuals occupationally not exposed to these metals. Preferably groups of 10-year-old children are to be used when only environmental pollution is to be taken into account. Hair samples are incomparably easier to collect, transport and store than the alternative biological material such as blood and urine used commonly to demonstrate exposure to various toxic agents. Biological monitoring of environmental pollution cannot replace the standard procedures of measuring air, water and soil pollution; however, the technique appears to have the potential of being an effective tool search for the extent of environmental pollution and for delimitation of territorial boundaries of areas affected most by hazardous emissions containing potentially toxic trace elements.

[Three new cases of pulmonary fibrosis in finishers of tools reinforced with tungsten carbide (author's transl)]. / A propos de trois nouveaux cas de fibrose pulmonaire chez des affûteurs d'outils renforcés au carbure de tungsténe.

On the basis of three new cases of pulmonary fibrosis due to heavy metals, the authors review the various clinical, radiological and respiratory function test criteria which lead to the diagnosis of this type of occupational fibrosis. This is an uncommon disease (21 cases published up to the present in France), insufficiently known, but with significant and sometimes severe risks. On July 19th 1980, the disease was added to the list of occupational diseases with No 70.