Multiple drug resistance is a challenging issue in the clinic. There is growing evidence that the G-protein-coupled estrogen receptor (GPER) is a novel mediator in the development of multidrug resistance in both estrogen receptor (ER)-positive and -negative breast cancers, and that cancer-associated fibroblasts (CAFs) in the tumor microenvironment may be a new agent that promotes drug resistance in tumor cells. However, the role of cytoplasmic GPER of CAFs on tumor therapy remains unclear. Here we first show that the breast tumor cell-activated PI3K/AKT (phosphoinositide 3-kinase/AKT) signaling pathway induces the cytoplasmic GPER translocation of CAFs in a CRM1-dependent pattern, and leads to the activation of a novel estrogen/GPER/cAMP/PKA/CREB signaling axis that triggers the aerobic glycolysis switch in CAFs. The glycolytic CAFs feed the extra pyruvate and lactate to tumor cells for augmentation of mitochondrial activity, and this energy metabolically coupled in a 'host-parasite relationship' between catabolic CAFs and anabolic cancer cells confers the tumor cells with multiple drug resistance to several conventional clinical treatments including endocrine therapy (tamoxifen), Her-2-targeted therapy (herceptin) and chemotherapy (epirubicin). Moreover, the clinical data from F-fluorodeoxyglucose positron emission tomography/computed tomography further present a strong association between the GPER/cAMP/PKA/CREB pathway of stromal fibroblasts with tumor metabolic activity and clinical treatment, suggesting that targeting cytoplasmic GPER in CAFs may rescue the drug sensitivity in patients with breast cancer. Thus, our data define novel insights into the stromal GPER-mediated multiple drug resistance from the point of reprogramming of tumor energy metabolism and provide the rationale for CAFs as a promising target for clinical therapy.
Background This study assessed the treatment results of a series of 33 patients with squamous cell carcinoma (SCC) of the temporal bone and evaluated the efficacy of mastoidectomy combined with perioperative radiation therapy protocol. Methods Thirty‐three patients with biopsy‐proven SCC invaded to the temporal bone were reviewed retrospectively and staged into three subgroups according to the University of Pittsburgh TNM Staging System. There were 3 patients with Stage I and II disease(tumor confined to auditory canal), 17 patients with Stage III (tumor involving the middle ear or mastoid), and 13 patients with Stage IV(more extensive disease). Two patients were treated by surgery alone. Eleven patients received irradiation only, and the remaining 20 patients underwent combined surgery and perioperative radiotherapy. The surgical intervention included sleeve resection for patients with Stage I and II lesions and mastoidectomy for all patients with Stage III and IV lesions except 1 who had subtotal temporal bone resection. The radiation dose delivered was in the range of 3500∼10 000 cGy, with an average dose of 6560 cGy. Results The five‐year survival rate for the whole series was 51.7% by the life‐table analysis. After being staged into three subgroups (ie, Stage I + II, Stage III, and Stage IV), the estimated five‐year survival rates were 100%, 68.8%, and 19.6%, respectively (p = 0.04). Radiation alone yielded a 28.7% five‐year survival, while combined surgery and irradiation gave a result of 59.6% (p = 0.80). For patients treated with planned combined therapy, the actuarial five‐year survival rates were 72.7% (8/11) for Stage III disease and 12.5% (1/8) for Stage IV disease (p = 0.02). Twelve patients who died of disease did so of local recurrence (10 cases), cervical metastases (1 case), and liver metastases (1 case), with 70% of succumbing to their diseases within two years. Complications include osteonecrosis (n = 1), osteitis (n = 3), radiation dermatitis (n = 2), facial nerve palsy (n = 2), and delayed healing (n = 2). Data on clinical presentation and treatment modality were also analyzed. Conclusion The results of mastoidectomy with removal of all gross tumor, combined with planned perioperative irradiation therapy, seems to be a useful approach for SCC of the temporal bone. This gives at least as good, and possibly better, five‐year survival than temporal bone resection. The mastoidectomy procedure creates less operative morbidity and mortality. To facilitate the development of more effective means of treating advanced disease, an accepted staging system and cooperative group investigation is necessary. © 1999 John Wiley & Sons, Inc. Head Neck 21: 461–466, 1999.
xing Qin \s=b\A retrospective evaluation was done on 120 patients treated for parotid cancer. The aim of the study was to establish the role of postoperative radiation therapy. Fifty-nine patients were treated by surgery alone and an equal number of patients received surgery plus postoperative radiation therapy. Two patients were treated by preoperative irrradiation. The overall 5-, 10-, and 15-year survival rates were 81%, 62%, and 65%, respectively. Postoperative radiation therapy proved to increase local control over surgery alone whenever (1) there was locally advanced disease, (2) the tumor belonged to a so\ x=req-\ called poorly differentiated variety, (3) the treatment was given for a recurrent lesion, and/or (4) there was tumor involvement of the facial nerve. It did not appear that postoperative radiation therapy increased the survival for patients with low-grade malignant tumors. Radiation therapy should be given as early as possible after surgery and the optimum dose ranges from 3,000 to 5,000 rad given in three to five weeks, respectively.
There is no need for a comprehensive neck dissection for N0 supraglottic laryngeal cancer. A selective neck dissection such as UND (level II) or a supraomohyoid neck dissection (sparing the submandibular region) of level II and III will serve the purpose of radical neck treatment for the supraglottic cancer.
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