Association of longer telomere length in cancer cells and cancer-associated fibroblasts with worse prognosis.

Background: Telomere dysfunction has been reported to be directly involved in carcinogenesis owing to chromosomal instability and immortalization; however, the clinicopathological significance of telomeres remains controversial. We have shown that telomere shortening occurs in normal-appearing duct cells at initiation and then continues during the progression of pancreatic cancer. In this study, we determined the clinicopathological and prognostic value of telomere length (TL) in cancer progression.

GAREM1 is involved in controlling body mass in mice and humans.

The adaptor protein GAREM has two subtypes. Each is involved in Erk activation signaling downstream of the cell growth factor receptor in cultured cells. Regarding their role in individual animals, we have previously reported that mice deficient in GAREM2, which is highly expressed in the brain, exhibit emotional changes.

An International Collaborative Animal Study of the Carcinogenicity of Mobile Phone Radiofrequency Radiation: Considerations for Preparation of a Global Project.

Radiofrequency radiation (RFR) was classified as a "possible" human carcinogen in 2011, which caused great public concern. A carcinogenicity study by the National Toxicology Program (NTP) found Code Division Multiple Access-and Global System for Mobile Communications-modulated mobile phone RFR to be carcinogenic to the brain and heart of male rats. As part of an investigation of mobile phone carcinogenesis, and to verify the NTP study results, a 5-year collaborative animal project was started in Korea and Japan in 2019.

Relationship between Lung Carcinogenesis and Chronic Inflammation in Rodents.

Lung cancer remains the leading cause of cancer-related deaths, with an estimated 1.76 million deaths reported in 2018. Numerous studies have focused on the prevention and treatment of lung cancer using rodent models.

Single Intratracheal Quartz Instillation Induced Chronic Inflammation and Tumourigenesis in Rat Lungs.

Crystalline silica (quartz) is known to induce silicosis and cancer in the lungs. In the present study, we investigated the relationship between quartz-induced chronic inflammation and lung carcinogenesis in rat lungs after a single exposure to quartz. F344 rats were treated with a single intratracheal instillation (i.

Preexisting diabetes mellitus had no effect on the no-observed-adverse-effect-level of acetaminophen in rats.

Information on the safety of chemical substances in patients with various preexisting conditions remains limited. Acetaminophen was added to the basal diet at 0, 80, 253, 800, 2530, or 8000 ppm and administered to type 2 diabetes mellitus rats (GK/Jcl) and the control male rats (Wistar) for 13 weeks. Both strains treated with 8000 ppm acetaminophen (561.

Lung proliferative lesion-promoting effects of left pulmonary ligation in A/J female mice.

This present study was conducted in an attempt to examine proliferative lesion-promoting effect in the lung by compensatory lung growth after left pulmonary ligation. To examine a strong proliferative lesion-promoting effect in the lung, the effects of left pulmonary ligation on lung proliferative lesions induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were examined for 12 weeks. The number of proliferative lesions induced by NNK in the right lung after left pulmonary ligation increased significantly after 12 weeks, indicated by an increase in the weight of the right lung.

Effects of the expectorant drug ambroxol hydrochloride on chemically induced lung inflammatory and neoplastic lesions in rodents.

Ambroxol hydrochloride (AH) is an expectorant drug used to stimulate pulmonary surfactant and serous airway secretion. Surfactant proteins (SPs) are essential for maintaining respiratory structure and function, although SP expression has also been reported in lung inflammatory and proliferative lesions. To determine whether AH exerts modulatory effects on these lung lesions, we examined its effects on pleural thickening induced by intrathoracic administration of dipotassium titanate (TISMO) in A/JJmsSlc (A/J) mice.

Characteristics of surfactant proteins in tumorigenic and inflammatory lung lesions in rodents.

Surfactant proteins (SPs) are essential for the proper structure and respiratory function of the lungs. There are four subtypes of SPs: SP-A, SP-B, SP-C, and SP-D. The expectorant drug ambroxol hydrochloride is clinically used to stimulate pulmonary surfactant and airway serous secretion.

γH2AX is immunohistochemically detectable until 7 days after exposure of N-bis (2-hydroxypropyl) nitrosamine (DHPN) in rat lung carcinogenesis.

It is known that γH2AX, which is formed when there is a double-strand break in DNA, can act as a sensitive marker of genomic instability. In this experiment, the time-course manner of the expression of γH2AX in the lung was examined in the early phase after treatment with a lung carcinogen, N-bis (2-hydroxypropyl) nitrosamine (DHPN). The expression of γH2AX is expected to be one of the useful markers for lung carcinogenesis in early stages.

A 13-week subchronic toxicity study of acetaminophen using an obese rat model.

Although obesity is increasing worldwide, experimental studies examining the possible association between obesity and susceptibility to chemical toxicity are limited. In the present study, we performed a 13-week toxicity study for acetaminophen (APAP), a well-known drug that exhibits hepatotoxicity as an adverse effect, using an obese rat model to investigate the differences in susceptibility between obese and normal individuals. Male F344 and obese Zucker (lean and fatty) rats were administered 0, 80, 253, 800, 2,530, or 8,000 ppm APAP in the diet for 13 weeks.

Hepatocyte growth factor produced in lung fibroblasts enhances non-small cell lung cancer cell survival and tumor progression.

Background: The influence of lung fibroblasts on lung cancer progression is not fully understood.

Methods: Lung fibroblasts (HFL1, MRC5, and IMR90 cells) and non-small cell lung cancer (NSCLC)-derived cell lines (A549, EBC1, and HI1017) were cultured under serum-free conditions, and the resulting culture media were designated "cell-conditioned media". Cell survival (viability) was assessed by WST-1 assay.

Validating the use of napsin A as a marker for identifying tumorigenic potential of lung bronchiolo-alveolar hyperplasia in rodents.

There are two types of bronchiolo-alveolar hyperplasia (hyperplasia) in rodent lungs. The first is "inflammatory hyperplasia" that retains its ability to revert to normal epithelia upon removal of the stimulating insult. The second is "latent tumorigenic hyperplasia", which is irreversible and causes independent preneoplastic lesions that can progress to bronchiolo-alveolar adenocarcinoma.

Suppressive effects of the expectorant drug ambroxol hydrochloride on quartz-induced lung inflammation in F344 rats.

Surfactant proteins (SPs) are essential to respiratory structure and function. The expectorant drug ambroxol hydrochloride is clinically prescribed to stimulate pulmonary surfactant and airway serous secretion. Therefore, ambroxol hydrochloride may affect SP production and pulmonary inflammation.

Altered susceptibility of an obese rat model to 13-week subchronic toxicity induced by 3-monochloropropane-1,2-diol.

3-Monochloropropane-1,2-diol (3-MCPD) is a heat-induced food contaminant that has been shown to be a nongenotoxic renal carcinogen. Although the toxicity of 3-MCPD has been widely investigated for decades, there is a further concern that 3-MCPD might exert more potent toxicity in high-risk population with underlying diseases such as hyperlipidemia associated with obesity. In the present study, we performed a 13-week subchronic toxicity study for 3-MCPD using an obesity rat model to investigate the differences in susceptibility between obese and normal individuals.

Chronic mesothelial reaction and toxicity of potassium octatitanate fibers in the pleural cavity in mice and F344 rats.

Fiber-shaped particles of potassium octatitanate (tradename TISMO; chemical formula K2 O·6TiO2 ), which are morphologically similar to asbestos particles, were shown to induce severe proliferative reactions in the pleural mesothelium in a previous experiment carried out over 21 weeks. The present study aims to determine whether these fibers induce malignant mesotheliomas in rodents, and to examine chronic toxicity induced. Additionally, we investigated the specific differences observable between the biological responses to the direct infusion of the fibers alone into the pleural cavity and those induced by the co-administration of the fibers with a known carcinogen.

Activation of MEK1/2-ERK1/2 signaling during NNK-induced lung carcinogenesis in female A/J mice.

The extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway is activated by several growth factors and mitogens, and upregulation has been noted in many human cancers, including examples in the lung. In this study, to study the association of ERK1/2 activation with mutation of Kras encoding an upstream activator of ERK1/2 in lung premalignant lesions, we immunohistochemically examined expression of phosphorylated forms of ERK1/2 (pERK1/2) and MAP/ERK kinase 1/2 (pMEK1/2) proteins and correlation between ERK activation and mutation of Kras encoding an upstream activator of ERK1/2, in a mouse lung carcinogenesis model. Female 7-week-old A/J mice were administered a single dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), then maintained without additional treatment until sacrifice at week 52.

An Autopsy Case of Rapidly Progressing Spindle Cell Carcinoma of the Lung Accompanied with Intratumor Hemorrhage.

Background: Spindle cell carcinoma (SPCC) of the lung is a subset of sarcomatoid carcinoma. Its clinical features are unclear because of its rarity. Here, we report an autopsy case of SPCC and review CT findings and chemotherapeutic regimens based on previous reports of this disease.

Long-Term Chronic Toxicity and Mesothelial Cell Reactions Induced by Potassium Octatitanate Fibers (TISMO) in the Left Thoracic Cavity in A/J Female Mice.

The present study was conducted to examine the chronic effects of potassium octatitanate fibers (trade name TISMO; chemical formula K2O·6TiO2) on the mouse lung and thoracic cavity. This method of infusion was employed to examine the direct effects of the fibers to the pleura. In the present study, 52- and 65-week experiments were employed to examine the long-term chronic effects after infusion of fiber-shaped TISMO into the thoracic cavities of A/J mice.

Immunohistochemical characteristics of surfactant proteins a, B, C and d in inflammatory and tumorigenic lung lesions of f344 rats.

Surfactant proteins (SPs), originally known as human lung surfactants, are essential to respiratory structure and function. There are 4 subtypes, SP-A, SP-B, SP-C and SP-D, with SP-A and SP-D having immunological functions, and SP-B and SP-C having physicochemical properties that reduce the surface tension at biological interfaces. In this experiment, the expressions of SP-A, SP-B, SP-C and SP-D in lung neoplastic lesions induced by N-bis (2-hydroxypropyl) nitrosamine (DHPN) and inflammatory lesions due to quartz instillation were examined and compared immunohistochemically.

Significance of the progesterone receptor and epidermal growth factor receptor, but not the estrogen receptor, in chemically induced lung carcinogenesis in female A/J mice.

In the present study, the expression levels of female hormone receptors, estrogen receptor (ER) and progesterone receptor (PR) and the epidermal growth factor receptor, (EGFR), as well as proliferating cell nuclear antigen (PCNA) were examined in lung tumors that were induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in female A/J mice. Each seven-week-old mouse was administered with 2 mg NNK via intraperitoneal injection and the mice were subsequently euthanized at week 52. Lung tumors, including adenomas, carcinomas in adenomas and adenocarcinomas, were obtained and analyzed by immunohistochemistry for the expression levels of the receptors, ER, PR and EGFR, and PCNA.

[A case of advanced gastric cancer with multiple liver metastases treated with preoperative TS-1/CDDP chemotherapy and resection, with a complete response and survival for 7 years].

An 82-year-old man died because of squamous cell carcinoma of the right lung with metastasis to the left femoral bone. At the age of 75 years, he was admitted to our hospital because of hematemesis. Widespread type 3 gastric cancer was detected in the lesser curvature.

Rat strain differences in levels and effects of chronic inflammation due to intratracheal instillation of quartz on lung tumorigenesis induced by DHPN.

Chronic inflammatory effects of single intratracheal instillation (i.t.) of quartz on rat lung tumorigenesis were examined using 4 different animal models.

The peroxisome proliferator-activated receptor (PPAR) α agonist fenofibrate suppresses chemically induced lung alveolar proliferative lesions in male obese hyperlipidemic mice.

Activation of peroxisome proliferator-activated receptor (PPAR) α disrupts growth-related activities in a variety of human cancers. This study was designed to determine whether fenofibrate, a PPARα agonist, can suppress 4-nitroquinoline 1-oxide (4-NQO)-induced proliferative lesions in the lung of obese hyperlipidemic mice. Male Tsumura Suzuki Obese Diabetic mice were subcutaneously injected with 4-NQO to induce lung proliferative lesions, including adenocarcinomas.