Insulin-like growth factor 1 receptor (IGF1R) has been intensively investigated in many preclinical studies using cell lines and animal models, and the results have provided important knowledge to help improve the understanding of cancer biology. IGF1R is highly expressed in patients with lung cancer, and high levels of circulating insulin-like growth factor 1 (IGF1), the main ligand for IGF1R, increases the risk of developing lung malignancy in the future. Several phase I clinical trials have supported the potential use of an IGF1R-targeted strategy for cancer, including lung cancer. However, the negative results from phase III studies need further attention, especially in selecting patients with specific molecular signatures, who will gain benefits from IGF1R inhibitors with minimal side effects. This review will discuss the basic concept of IGF1R in lung cancer biology, such as epithelial-mesenchymal transition (EMT) induction and cancer stem cell (CSC) maintenance, and also the clinical implications of IGF1R for lung cancer patients, such as prognostic value and cancer therapy resistance.

Among all types of cancer, incidence of lung cancer remains the highest with regard to cancer-related mortality. Problems contributing to recurrence of the disease include metastasis and drug resistance. Mounting evidence has demonstrated involvement of epithelial mesenchymal transition (EMT) in cancer progression. EMT is a critical mechanism ensuring tissue remodeling during morphogenesis of multicellular organisms. Therefore, understanding of the biology of this process for identification of potential EMT-targeted therapeutic strategies for the benefit cancer patients is necessary. This review describes recent evidence of EMT involvement in drug resistance and metastasis of cancers, with an emphasis on lung cancer.
Biology ; Drug Resistance ; Epithelial-Mesenchymal Transition ; Humans ; Incidence ; Lung ; Lung Neoplasms ; Morphogenesis ; Neoplasm Metastasis ; Recurrence

Hypoxia, defined as a decrease of tissue oxygen levels, represents a fundamental pathophysiological condition in the microenvironment of solid tumors. Tumor hypoxia is known to be associated with radio/chemo-resistance and metastasis that eventually lead to cancer progression contributing to poor prognosis in cancer patients. Among transcription factors that accumulated under hypoxic conditions, hypoxia-inducible factor-1 (HIF-1) is a master transcription factor that has received the most intense attention in this field of research due to its capacity to modulate several hundred genes. With a clearer understanding of the HIF-1 pathway, efforts are directed at manipulation of this complex genetic process in order to ultimately decrease cellular HIF-1 levels. Some novel agents have been shown to have HIF-1 inhibition activity through a variety of molecular mechanisms and have provided promising results in the preclinical setting.
Anoxia ; Genetic Processes ; Humans ; Neoplasm Metastasis ; Oxygen ; Prognosis ; Transcription Factors

Hypoxia, defined as a decrease of tissue oxygen levels, represents a fundamental pathophysiological condition in the microenvironment of solid tumors. Tumor hypoxia is known to be associated with radio/chemo-resistance and metastasis that eventually lead to cancer progression contributing to poor prognosis in cancer patients. Among transcription factors that accumulated under hypoxic conditions, hypoxia-inducible factor-1 (HIF-1) is a master transcription factor that has received the most intense attention in this field of research due to its capacity to modulate several hundred genes. With a clearer understanding of the HIF-1 pathway, efforts are directed at manipulation of this complex genetic process in order to ultimately decrease cellular HIF-1 levels. Some novel agents have been shown to have HIF-1 inhibition activity through a variety of molecular mechanisms and have provided promising results in the preclinical setting.
Anoxia ; Genetic Processes ; Humans ; Neoplasm Metastasis ; Oxygen ; Prognosis ; Transcription Factors

Tobacco consumption is a major causative agent for various deadly diseases such as coronary artery disease and cancer. It is the largest avoidable health risk in the world, causing more problems than alcohol, drug use, high blood pressure, excess body weight or high cholesterol. As countries like Indonesia prepare to develop national policy guidelines for tobacco harm reduction, the scientific community can help by providing continuous ideas and a forum for sharing and distributing information, drafting guidelines, reviewing best practices, raising funds, and establishing partnerships. We propose several strategies for reducing tobacco consumption, including advertisement interference, cigarette pricing policy, adolescent smoking prevention policy, support for smoking cessation therapy, special informed consent for smokers, smoking prohibition in public spaces, career incentives, economic incentives, and advertisement incentives. We hope that these strategies would assist people to avoid starting smoking or in smoking cessation.
Adolescent ; Body Weight ; Cholesterol ; Coronary Artery Disease ; Financial Management ; Harm Reduction* ; Hope ; Humans ; Hypertension ; Indonesia* ; Informed Consent ; Motivation ; Practice Guidelines as Topic ; Smoke ; Smoking ; Smoking Cessation ; Tobacco Products ; Tobacco Use ; Tobacco*

The peak (dPower/dt), the maximum value of dPower/dt calculated by differentiation of ventricular power with respect to time, is verified from the physiological studies to be quite useful index indicating the ventricular contractility independent of the pre- and afterloads. However, the index has the disadvantage in the clinical application that it can not be measured by a non-invasive method. In the present study, peak (dPower/dt) could successfully be determined in a non-invasive manner as the product of aortic flow as measured with an ultrasonic pulsed Doppler flowmeter and brachial blood pressure as measured with cuff in the new apparatus. Involved in this study were 21 children, 52 adults with normal cardiac performance and 11 adult patients with coronary artery disease. The measurement of the index was successfully carried out in 28 of 61 adults and especially 16 of 21 children. The results of the study are summarized as follows:
1. Power waveform is similar to blood flow waveform and is little influenced by blood pressure waveform.
2, Peak (dPower/dt) can be determined as product of peak rate of change of aortic flow (peak (dF/dt) ) and mean brachial blood pressure without resorting to measurement of blood pressure waveform.
3. Peak (dPower/dt) was found significantly lower in cases having an ejection fraction less than 50% (93.5 J/sec²) than in those showing an ejection fraction of above 50% (145.3 J/sec²) (p<0.001) .
4. Peak (dPower/dt) normalized with body surface area was not significantly different from 8 years old children (80.2 J/sec²/m²) and 21-34 years old adults (88.0 J/sec²/m²) . According to this index, the cardiac contractility of 8 yearus old children seemed to reach the adult level.
From these findings it is concluded that the non-invasive method of determining a cardiologic parameter, peak (dPower/dt), as an index of cardiac contractility provides a means of salient clinical value.

This study aimed to estimate the cost-effectiveness of pregabalin treatment for neuropathic pain.
Design:Long-term simulations based on state transition models.
Methods:We examined the cost-effectiveness of pregabalin for treatment of three common peripheral neuropathic pains, postherpetic neuralgia(PHN), painful diabetic peripheral neuropathy(DPN), and radiculopathy, using the incremental cost-effectiveness ratio(ICER). We used quality-adjusted life years(QALYs)as an index of effectiveness, and also estimated medical costs. For PHN and DPN, we constructed state transition models comprising two states, with and without pregabalin treatment, and performed 52-week simulations. The pain scores reported in Japanese phaseIII studies were used to set patients' weekly pain scores. The results of utility surveys conducted overseas were used as utility scores, while values randomly sampled from probability distributions were used to set weekly pain scores and drop-out rates. In base-case analyses, we performed 1000 1st-order Monte Carlo simulations using 1000 values randomly sampled from probability distributions, and calculated QALYs and medical costs for 52 weeks for each group. For radiculopathy, the ICER was calculated from changes in QALYs for 12 weeks reported overseas and medical costs estimated separately for the identical period.
Results:The ICERs for PHN, DPN, and radiculopathy were 1,116,886 Yen/QALY, 1,100,420 Yen/QALY, and 1,095,943 Yen/QALY, respectively, which were well below the upper limits of ICER ranges for treatments considered cost-effective. There were no cases in which ICERs obtained from scenario and sensitivity analyses differed significantly.
Conclusion:Pregabalin was shown to be cost-effective treatment for neuropathic pain.

It was reported that nerve fibers were present in the inner part of lumbar intervertebral discs from patients with discogenic pain. Because there are no nerve fibers in the inner part of annulus fibrosus in normal condition, this finding suggests nerve ingrowth into the disc may be a cause of discogenic pain. Disc degeneration is often asymptomatic, thus, to understand the differences between symptomatic and asymptomatic disc, it is necessary to understand the pathogenesis of discogenic pain. We recently revealed that over 90% of the nociceptive dorsal root ganglion (DRG) neurons innervating the disc are sensitive to nerve growth factor (NGF), which is related to inflammatory pain. This indicates that discogenic pain is closely related to inflammation and NGF may play a key role. The increase of inflammatory mediators in symptomatic discs has been reported; we therefore studied the effects of disc inflammation and found that it induces sensitization of disc-innervating neurons and nerve ingrowth into the disc. More recently, it was shown that annular rupture induces nerve ingrowth, an increase of inflammatory mediators in the disc, and upregulation of calcitonin gene-related peptide, a pain-related molecule in DRGs. These findings led us to believe that annular rupture triggers inflammation and nerve ingrowth, inflammatory mediators then further promote nerve ingrowth into the disc and sensitization of disc-innervating neurons, and discogenic pain finally becomes chronic. NGF, found in symptomatic discs, may act as a key factor in generating chronic discogenic pain by sensitizing disc-innervating neurons and stimulating nerve ingrowth into the disc.
Calcitonin Gene-Related Peptide ; Diagnosis-Related Groups ; Ganglia, Spinal ; Humans ; Inflammation ; Intervertebral Disc ; Intervertebral Disc Degeneration ; Nerve Fibers ; Nerve Growth Factor ; Neurons ; Rupture ; Up-Regulation

1）We had the opportunity to study medical education in Thailand and Singapore while we visited medical schools in those countries as a member of the Japan Tropical Medicine Association.
2）In Thailand, undergraduate medical education last for 6 years, which is the same length as in Japan. All lectures are in English. Medical students in Thailand are more deeply related to patients at bedside learning than are students in Japan. In Singapore, undergraduate education lasts for 5 years, and lectures are in English. In the third year, medical students start clinical medicine. Recently, a new program has been adopted in which medical students can easily choose their specialties right after graduation.
3）Japanese medical students study medicine in Japanese. In contrast, greater emphasis should be placed in Japan on medical education in English.

STUDY DESIGN: Retrospective observational study. PURPOSE: We examined change in lumbrosacral spine alignment and low back pain (LBP) following total hip arthroplasty (THA) in patients with severe hip osteoarthritis (OA). OVERVIEW OF LITERATURE: Severe hip osteoarthritis has been reported to cause spine alignment abnormalities and low back pain, and it has been reported that low back pain is improved following THA. METHODS: Our target population included 30 patients (29 female, mean age 63.5 years) with hip OA who underwent direct anterior approach THA. There were 12 cases with bilateral hip disease and 18 cases with unilateral osteoarthritis. Visual analogue scale (VAS) scores for LBP and coxalgia, the Roland-Morris Disability Questionnaire (RDQ), and the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) were assessed before and after surgery. Spinal alignment metrics were measured before and after surgery. RESULTS: VAS for LBP change from preoperative to final postoperative observation was significantly improved (p < 0.05), as was VAS for hip pain (p < 0.001). RDQ improved significantly (p < 0.01). All five domains of JOABPEQ were significantly improved (p < 0.05). In terms of coronal alignment, lumbar scoliosis change from preoperative to last observation was significantly reduced (p < 0.05). There were no significant changes in the sagittal alignment metrics. In addition, there was a correlation between before and after RDQ difference and before and after lumbar scoliosis difference (p < 0.05). VAS for LBP (p < 0.05) as well as RDQ (p < 0.05) were significantly improved only in unilateral OA. Lumbar scoliosis was significantly improved in cases of unilateral OA (p < 0.05), but alignment did not improve in cases of bilateral OA (p=0.29). CONCLUSIONS: The present study demonstrates improvements in VAS for LBP, RDQ, and all domains of JOABPEQ. There were also significant reductions in lumbar scoliosis and an observed correlation of RDQ improvement with lumbar scoliosis improvement. We were able to observe improvements in lumbar scoliosis and low back pain only in cases of unilateral OA. It has been suggested that the mechanism of low back pain improvement following THA is related to compensatory lumbar scoliosis improvement.
Arthroplasty ; Arthroplasty, Replacement, Hip ; Asian Continental Ancestry Group ; Back Pain ; Female ; Health Services Needs and Demand ; Hip ; Humans ; Low Back Pain ; Observational Study ; Osteoarthritis ; Osteoarthritis, Hip ; Retrospective Studies ; Scoliosis ; Spine