Oncogene addiction is a cellular property by which cancer cells become highly dependent on the expression of oncogenes for their survival. Oncogene addiction can be exploited to design molecularly targeted drugs that kill only cancer cells by inhibiting the specific oncogenes. Genes and cell lines exhibiting oncogene addiction, as well as the mechanisms by which cell death is induced when addicted oncogenes are suppressed, have been extensively studied. However, it is still not fully understood how oncogene addiction is acquired in cancer cells. Here, we take a synthetic biology approach to investigate whether oncogenic mutation or oncogene expression suffices to confer the property of oncogene addiction to cancer cells. We employed human mammary epithelium-derived MCF-10A cells expressing the oncogenic KRAS or BRAF. MCF-10A cells harboring an oncogenic mutation in a single-allele of KRAS or BRAF showed weak transformation activity, but no characteristics of oncogene addiction. MCF-10A cells overexpressing oncogenic KRAS demonstrated the transformation activity, but MCF-10A cells overexpressing oncogenic BRAF did not. Neither cell line exhibited any oncogene addiction properties. These results indicate that the introduction of oncogenic mutation or the overexpression of oncogenes is not sufficient for cells to acquire oncogene addiction, and that oncogene addiction is not associated with transformation activity.
The degree of hepatopathy affecting the synthesis of α 2-macroglobulin (α2M) as an acute phase protein in rats was investigated. Hepatopathy was induced in Sprague-Dawley rats by intravenous administration of galactosamine at a dose of 30 mg/kg for 7 days. Inflammation was induced by intramuscular injection of turpentine oil at a dose of 2 mL/kg. Blood was collected before turpentine oil injection and at 24, 48, 72 and 96 h after injection. Serum concentrations of α2M were measured by enzyme-linked immunosorbent assay. Mean values of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in rats administered galactosamine were significantly higher than in controls. Mean values of body weight and total protein were significantly lower than in controls. Serum concentrations of α2M in the galactosamine group were significantly lower than in controls. Kinetic parameters, area under the concentration-time curve (AUC 0-96) and maximum serum concentration (Cmax), were significantly lower than in controls. The cutoff value for detecting the effects on synthesis of α2M in liver was 46.9 mgˑh/mL. Seven rats (77.8%) were assessed for decreases in the synthesis of α2M due to hepatopathy. Two rats showed no influence on the synthesis of α2M, despite administration of galactosamine. AST and ALT in these two rats were ≤ 285 and ≤ 174 U/L, respectively. In conclusion, synthesis of α2M in rats is evidently suppressed in the severe stages of hepatopathy.
SummarySyphacia muris is a ubiquitous nematode parasite and common contaminant of laboratory rats. A lthough S. muris infection is considered symptomless, it has some effects on the host's immunity and therefore can interfere with experimental settings and interrupt fi nal results. However, the molecular mechanisms involved in the alteration within the host's immunity remain unclear because of the absence of information about mRNA expressed in this parasite. In this study we performed the tr anscriptome profi ling of S. muris by next-generation sequencing. After de novo assembly and annotation, 14,821 contigs were found to have a sequence homology with any nematode sequence. Gene ontology analysis showed that the majority of the expressed genes are involved in cellular process, binding, and catalytic activity. Although the rate of expressed genes involved in the immune system was low, we found candidate genes that might be involved in the alteration within the host's immunity by regulating the host's innate immune response.
Niigata City in Japan and Khabarovsk City in Russia signed a sister city agreement in 1965 and have been interacting with each other for a long time. We have been conducting comparative research on the elderly between the two cities, but there is no research on the young. Distorted perception of body weight and unnecessary dieting behavior in adolescent girls is considered a problem in both Japan and Russia. Therefore, the purpose of this study was to clarify the distortion of weight perception and diet behavior of adolescent girls in both the countries. In addition, it was decided to investigate the eating habits of people in both the countries. In total, 195 15-year-old girls from Niigata, Japan (October 2020) and 286 girls from Khabarovsk, Russia (February 2017) were surveyed. The questionnaire used was an excerpt from the World Health Organization survey on the health behavior of school-age children. The proportion of Japanese adolescent girls who perceived themselves as overweight (distorted body weight perception) was 60.5%, which was significantly higher than that of Russian adolescent girls at 30.1% (p < 0.001). In addition, the prevalence of weight loss behavior in Japan was 34.9% (n = 68), which was significantly higher than that in Russia with 27.3% (n = 78) (p < 0.001). Adolescent girls in Japan had more serious problems with weight perception, but had fewer problems with breakfast and vegetable intake habits than those in Russia. From a young age, perception of correct body shape and establishment of eating habits are important not only for current health but also for future health.
Oncogene addiction is a cellular property by which cancer cells become highly dependent on the expression of oncogenes for their survival. Oncogene addiction can be exploited to design molecularly targeted drugs that kill only cancer cells by inhibiting the specific oncogenes. Genes and cell lines exhibiting oncogene addiction, as well as the mechanisms by which cell death is induced when addicted oncogenes are suppressed, have been extensively studied. However, it is still not fully understood how oncogene addiction is acquired in cancer cells. Here, we take a synthetic biology approach to investigate whether oncogenic mutation or oncogene expression suffices to confer the property of oncogene addiction to cancer cells. We employed human mammary epithelium-derived MCF-10A cells expressing the oncogenic KRAS or BRAF. MCF-10A cells harboring an oncogenic mutation in a single-allele of KRAS or BRAF showed weak tumorigenic activity, but no characteristics of oncogene addiction. MCF-10A cells overexpressing oncogenic KRAS demonstrated the tumorigenic activity, but MCF-10A cells overexpressing oncogenic BRAF did not. Neither cell line exhibited any oncogene addiction properties. These results indicate that the introduction of oncogenic mutation or the overexpression of oncogenes is not sufficient for cancer cells to acquire oncogene addiction, and that oncogene addiction is not associated with tumorigenic potential.
SummaryThe novel WBN/Kob-Lepr fa (fa/fa) congenic rat strain is considered a useful rat model of type 2 diabetes mellitus (T2DM). Accumulating fi ndings suggest that low-grade infl ammation is a causative factor in T2DM and that circulating levels of infl ammatory cytokines are associated with insulin resistance. However, infl ammatory cytokine profi les and their correlations with T2DM development/ progression in fa/fa rats have not been studied. In this study, we found that the fa/fa rats had considerably high plasma levels of interleukin (IL)-1α. Abundant cecal IL-1α mRNA expression and cecal infl ammation with infi ltrating IL-1α-producing macrophages was observed in fa/fa rats. Bone marrow derived macrophages from fa/fa rats expressed high levels of IL-1α upon lipopolysaccharide stimulation. Furthermore, Syphacia muris infection, which delays the onset of T2DM, reduced both plasma and cecal IL-1α levels in fa/fa rats. These results suggest that macrophage infi ltration and IL-1α secretion comprise an important part of T2DM development and that S. muris infection inhibits pro-infl ammatory cytokine expression in fa/fa rats.
A 15-year-old neutered male domestic shorthair cat presented with a 2-month history of stridor, snoring, hoarseness, dysphagia and weight loss. Non-anesthetized contrast computed tomography of the head revealed a heterogeneous enhanced mass which was suspected as a malignant tumor the oropharynx, extending from the caudal soft palate. Fine needle aspiration under anesthesia was performed from deep tissue of the mass. Cytology revealed cells consistent with squamous cell carcinoma. The patient was treated with toceranib (10 mg/cat, p.o., EOD or thrice weekly) and meloxicam (0.025-0.300 mg/kg, s.c. or p.o., SID, EOD or thrice weekly). Radiologically, the cancer resolved almost completely by day 8. The cancer recurred after 13 days of meloxicam suspension. Progression-free survival was 30 days. The range of creatinine was 1.83-3.39 mg/dL during follow-up. This is the rst reported case of an oropharyngeal squamous cell carcinoma in a cat treated with combinational therapy of toceranib and high dose meloxicam.
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