Cooperation of Cancer Stem Cell Properties and Epithelial-Mesenchymal Transition in the Establishment of Breast Cancer Metastasis

Epithelial-mesenchymal transition (EMT) is a multistep process in which cells acquire molecular alterations such as loss of cell-cell junctions and restructuring of the cytoskeleton. There is an increasing understanding that this process may promote breast cancer progression through promotion of invasive and metastatic tumor growth. Recent observations imply that there may be a cross-talk between EMT and cancer stem cell properties, leading to enhanced tumorigenicity and the capacity to generate heterogeneous tumor cell populations. Here, we review the experimental and clinical evidence for the involvement of EMT in cancer stem cell theory, focusing on the common characteristics of this phenomenon

Bevacizumab terminates homeobox B9-induced tumor proliferation by silencing microenvironmental communication

Background: Homeobox B9 (HOXB9), a transcriptional factor, regulates developmental processes and tumor progression and has recently been recognized as one of important transcriptional factors related to angiogenesis. This study aimed to investigate the role of HOXB9 in tumorigenesis and angiogenesis. Methods: We examined the expression of HOXB9 in colorectal cancer using qPCR and in situ hybridization. We also examined the effect of HOXB9 overexpression in colorectal cancer using a proliferation assay, ELISA, a multiplex assay, and xenograft models. The clinical significance of HOXB9 was statistically evaluated in resected specimens. Results: HOXB9 was expressed in colorectal cancer specimens. HOXB9 induced angiogenesis and tumor proliferation in vitro, which resulted in high tumorigenicity in vivo and poor overall survival. Bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, remarkably suppressed tumor proliferation by inhibiting angiogenesis in HOXB9-overexpressing xenografts, and it improved overall survival and provided prolonged progression-free survival in HOXB9-overexpressing patients. A comprehensive multiplex assay of the supernatant of cancer cells co-cultured with human vascular endothelial cells and fibroblasts indicated significantly higher interleukin-6 (IL6) levels than those in the supernatant of monocultured cells. HOXB9 overexpression in clinical specimens was significantly correlated with increased IL6 expression. An IL6-neutralizing antibody inhibited VEGF secretion and tumor proliferation in the co-culture system. Conclusions: HOXB9 promotes the secretion of angiogenic factors, including VEGF, to induce tumor proliferation through microenvironmental production of cytokines including IL6 signaling. Moreover, silencing of VEGF or IL6 terminates cytokine release in tumor microenvironment. Thus, HOXB9 and IL6 may be potential biomarkers for bevacizumab treatment

Open Access

Bevacizumab terminates homeobox B9-induced tumor proliferation by silencing microenvironmental communicatio

Laser-driven multi-MeV high-purity proton acceleration via anisotropic ambipolar expansion of micron-scale hydrogen clusters

強力なレーザーを使ってエネルギーがそろった純度100％の陽子ビーム発生に成功 --レーザー駆動陽子ビーム加速器の実現へ向けて大きく前進--. 京都大学プレスリリース. 2022-10-13.Multi-MeV high-purity proton acceleration by using a hydrogen cluster target irradiated with repetitive, relativistic intensity laser pulses has been demonstrated. Statistical analysis of hundreds of data sets highlights the existence of markedly high energy protons produced from the laser-irradiated clusters with micron-scale diameters. The spatial distribution of the accelerated protons is found to be anisotropic, where the higher energy protons are preferentially accelerated along the laser propagation direction due to the relativistic effect. These features are supported by three-dimensional (3D) particle-in-cell (PIC) simulations, which show that directional, higher energy protons are generated via the anisotropic ambipolar expansion of the micron-scale clusters. The number of protons accelerating along the laser propagation direction is found to be as high as 1.6 ±0.3 × 10⁹/MeV/sr/shot with an energy of 2.8 ±1.9 MeV, indicating that laser-driven proton acceleration using the micron-scale hydrogen clusters is promising as a compact, repetitive, multi-MeV high-purity proton source for various applications

Recent Development of Sentinel Lymph Node Biopsy for Breast Cancer in Japan

The number of breast cancer cases undergoing sentinel lymph node biopsy (SLNB) has been increasing with the number of articles published in Japan. SLNB using the dye method alone is performed in about one-third of patients. Analysis of questionnaire responses from 40 institutions in Japan revealed an identification rate by the dye method alone of 87%, compared with 96% using the combined method; the combined method is now recognized in Japan as superior to the dye method alone. No dyes have been specifically approved by the government for use in SLNB, and physicians have been using several inappropriate dyes as tracers for SLNB, such as indocyanine green, patent blue, indigo carmine, and isosulfan blue. The colloidal radiotracers used in Japan include tin colloid, stannous phytate, rhenium sulfate and human serum albumin. Albumin colloid and sulfur colloid are not commercially available in Japan. Small-size tin colloids, stannous phytate and rhenium sulfate all yield good results in terms of detection and false-negative rates. Provided that the surgeon has adequate experience in SLNB, a negative sentinel node can serve as a substitute for negative results from axillary lymph node dissection. Although many institutions have introduced SLNB, few reports have focused on the results of SLNB without axillary dissection because of short follow-up times and small number of patients. The final decision as to whether SLNB is an adequate substitute for axillary dissection awaits the results of prospective randomized trials

Recent Development of Sentinel Lymph Node Biopsy for Breast Cancer in Japan

The number of breast cancer cases undergoing sentinel lymph node biopsy (SLNB) has been increasing with the number of articles published in Japan. SLNB using the dye method alone is performed in about one-third of patients. Analysis of questionnaire responses from 40 institutions in Japan revealed an identification rate by the dye method alone of 87%, compared with 96% using the combined method; the combined method is now recognized in Japan as superior to the dye method alone. No dyes have been specifically approved by the government for use in SLNB, and physicians have been using several inappropriate dyes as tracers for SLNB, such as indocyanine green, patent blue, indigo carmine, and isosulfan blue. The colloidal radiotracers used in Japan include tin colloid, stannous phytate, rhenium sulfate and human serum albumin. Albumin colloid and sulfur colloid are not commercially available in Japan. Small-size tin colloids, stannous phytate and rhenium sulfate all yield good results in terms of detection and false-negative rates. Provided that the surgeon has adequate experience in SLNB, a negative sentinel node can serve as a substitute for negative results from axillary lymph node dissection. Although many institutions have introduced SLNB, few reports have focused on the results of SLNB without axillary dissection because of short follow-up times and small number of patients. The final decision as to whether SLNB is an adequate substitute for axillary dissection awaits the results of prospective randomized trials