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

Purpose: Bone is one of the most common sites of metastases in patients with advanced lung cancer. Skeletal complications may cause significant morbidity and decrease performance status (PS). Such complications, referred to as skeletal related events (SREs), include severe bone pain, pathological fractures, spinal cord compression, and hypercalcemia of malignancy. We assessed the clinical impact of SREs in non-small lung cancer (NSCLC) patients with bone metastases. Methods: We retrospectively investigated the clinical records of all 120 patients who were diagnosed advanced NSCLC with bone metastases between June 1998 and March 2009. Results: A total of 23 patients (26.7%) were found to have SREs at the time of initial diagnosis. The median survival time (MST) was 123 days for patients with SREs, while it increased to 276 days for those without SREs. The MST of the patients with SREs were significantly shorter than that of the patients without SREs (p<0.001). We also studied the SREs during clinical courses of 89 patients whose records were available over 3 months. A total of 39 patients (43.8%) were found to have SREs during clinical courses. Conclusion: The patients in NSCLC with bone metastases were often found to have SREs. SREs cause significant morbidity and deterioration of PS. Systemic chemotherapy could not decrease SREs during their clinical courses. Further studies evaluating bisphosphonates in combination with chemotherapy are warranted. Palliat Care Res 2010; 5(2): 145-151

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

Radical hysterectomy is a standard surgery to treat early-stage uterine cervical cancer. The Laparoscopic Approach to Cervical Cancer (LACC) trial has shown that patients receiving minimally invasive radical hysterectomy have a poorer prognosis than those receiving open radical hysterectomy; however, the reason for this remains unclear. The LACC trial had 2 concerns: the learning curve and the procedural effects. Appropriate management of the learning curve effect, including surgeons’ skills, is required to correctly interpret the result of surgical randomized controlled trials. Whether the LACC trial managed the learning curve effect remains controversial, based on the surgeons’ inclusion criteria and the distribution of institutions with recurrent cases. An appropriate surgical procedure is also needed, and avoiding intraoperative cancer cell spillage plays an important role during cancer surgery. Cancer cell spillage during minimally invasive surgery to treat cervical cancer is caused by several factors, including 1) exposure of tumor, 2) the use of a uterine manipulator, and 3) direct handling of the uterine cervix. Unfortunately, these issues were not addressed by the LACC trial. We evaluated the results of minimally invasive radical hysterectomy while avoiding cancer cell spillage for early-stage cervical cancer. Our findings show that avoiding cancer cell spillage during minimally invasive radical hysterectomy may ensure an equivalent oncologic outcome, comparable to that of open radical hysterectomy. Therefore, evaluating the importance of avoiding cancer cell spillage during minimally invasive surgery with a better control of the learning curve and procedural effects is needed.

Some simulation-based education tools have been introduced in Kampo medicine. However, there are only a few brief simulation tools to learn qi-blood-fluid (QBF) patterns of traditional Chinese medicine (TCM). In this study, we developed a self-diagnostic questionnaire that allows students learn TCM interviews and QBF patterns by answering the questionnaire and evaluated its reliability and validity. We extracted questionnaire items to classify six QBF patterns (qi deficiency, blood deficiency, yin deficiency, qi stagnation, blood stasis, and phlegm-fluid retention) based on some textbooks of TCM and Kampo medicine. Then we developed an initial questionnaire comprising 35 items. Fifth year medical students at Tohoku University School of Medicine answered the questionnaire of small group teaching during 2017-2020. We evaluated the accuracy of the questionnaire if compared with the diagnosis of academic supervisors. To improve the accuracy, we adjusted the questionnaire’s thresholds and created a predictive model of the patterns using logistic regression analysis. The questionnaire’s sensitivity improved by adjusting the thresholds. Logistic regression analysis resulted in a predictive model that could determine QBF patterns with the same level of accuracy as the original for 20 items overall. The results suggest that the use of a simple questionnaire with ensured accuracy may contribute to better pre-graduate education by making it easier for students to understand their own Kampo medicine patterns.