SWI/SNF family mutations in advanced NSCLC: genetic characteristics and immune checkpoint inhibitors' therapeutic implication.

BACKGROUND: SWItch/Sucrose NonFermentable (SWI/SNF) mutations have garnered increasing attention because of their association with unfavorable prognosis. However, the genetic landscape of SWI/SNF family mutations in Chinese non-small-cell lung cancer (NSCLC) is poorly understood. In addition, the optimal treatment strategy has not yet been determined. PATIENTS AND METHODS: We collected sequencing data on 2027 lung tumor samples from multiple centers in China to comprehensively analyze the genomic characteristics of the SWI/SNF family within the Chinese NSCLC population. Meanwhile, 519 patients with NSCLC from Sun Yat-sen University Cancer Center were enrolled to investigate the potential implications of immunotherapy on patients with SWI/SNF mutations and to identify beneficial subpopulations. We also validated our findings in multiple publicly available cohorts. RESULTS: Approximately 15% of Chinese patients with lung cancer harbored mutations in the SWI/SNF chromatin remodeling complex, which were mutually exclusive to the EGFR mutations. Patients with SWI/SNFmut NSCLC who received first-line chemoimmunotherapy had better survival outcomes than those who received chemotherapy alone (median progression-free survival: 8.70 versus 6.93 months; P = 0.028). This finding was also confirmed by external validation using the POPLAR/OAK cohort. SWI/SNFmut NSCLC is frequently characterized by high tumor mutational burden and concurrent TP53 or STK11/KEAP mutations. Further analysis indicated that TP53 and STK11/KEAP1 mutations could be stratifying factors in facilitating personalized immunotherapy and guiding patient selection. CONCLUSIONS: This study provides a step forward in understanding the genetic and immunological characterization of SWI/SNF genetic alterations. Moreover, our study reveals substantial benefits of immunotherapy over chemotherapy for SWI/SNF-mutant patients, especially the SWI/SNFmut and TP53mut subgroups.

Diagnosis and surgical treatment of carotid body tumors: 25 years' experience in China.

Carotid body tumors (CBT) are rare neoplasms arising from the small chemoreceptor organ in the adventitia of the common carotid bifurcation. A retrospective survey was conducted in 33 patients, treated by curative resection of the neoplasm, from 1980 to 2005, to investigate clinical features, preoperative treatment and surgical approach, and determine the optimum management for CBT. The demographic characteristics, clinical features, surgical approach and complications were documented and analyzed. Accurate diagnosis and effective preoperative training were associated with a good surgical outcome. Carotid arteriography accurately diagnoses and evaluates the brain's collateral circulation in the circle of Willis. Ultrasonography is useful. Carotid blood flow obstruction (Matas' training) is effective. Complete excision of the carotid system without a vascular replacement is possible only after reliable Matas' training and objective observation of the establishment of circulation in the circle of Willis. Correct treatment of the internal and common carotid artery is important to reduce postoperative complications. The continuity of the common and internal carotid artery should be retained if possible, and carotid artery repair is recommended. Minor complications occurred in five (15%) patients and one patient died from a cause not related to the CBT at follow-up.

A study of injectable tissue-engineered autologous cartilage.

OBJECTIVE: To test the effectiveness of the new techniques of tissue-engineered cartilage. METHODS: Chondrocytes were harvested through type II collagenase digestion from the auricle of New Zealand rabbits. The cells were mixed with alginate to generate chondrocytes/alginate composites with final cellular density of 50 x 10(6) per mL. Calcium chloride was used as the cross-linking agent to gel the aqueous alginate solution. The chondrocytes/alginate composites were injected into the dorsal subcutaneous tissue of New Zealand rabbits through autologous cells grafts. The specimens were observed during cartilage formation at 4, 8, and 12 weeks after injection. RESULTS: Prior to harvesting, chondrocytes/alginate composites were easily visualized under the dorsal skin of animals. The appearance of experimental specimens was similar to that of native cartilage in gross morphology. Using a standard hematoxylin and eosin stain, the histologic features of all experimental specimens demonstrated new cartilage formation. With a Masson's trichrome and safranin O stain, the presence of collagen and glycosaminoglycan (GAG) was observed at 8 and 12 weeks. CONCLUSION: This study demonstrated that polymerization of alginate hydrogel can be controlled to allow injection of chondrocytes that produce new autologous cartilage at subcutaneous dorsal site of rabbits. Injectable tissue-engineered autologous cartilage is promising for potential use in oral and maxillofacial surgery.

[Experimental study on osteoinduction of coral composited artificial bone].

OBJECTIVE: To improve the osteoinduction of coral and provide a perfect bone graft substitute for clinical bone defects. METHODS: By combining coral with collagen and recombinant human bone morphogenetic protein-2(rhBMP-2), coral/collagen/rhBMP-2 composite was obtained. The composite was implanted into the back muscle pouches of mice, and coral/collagen or coral/rhBMP-2 were implanted as control. The osteoinduction of the composite was assessed by histology and image analysis system. RESULTS: The chondrocyte differentiation and matrix formation were observed in local sites after one week, lamellar bone with bone marrow were formed after 4 weeks, and coral were absorbed partially. The quantity of osteoinduction was time-related and rhBMP-2 dose-related(P < 0.01). Coral/collagen and coral/rhBMP-2 implants did not show any bone or cartilage formation. CONCLUSION: The coral/collagen/rhBMP-2 composite possesses a superior osteoinduction and will be a new type of bone substitute to be used in orthopedic and maxillofacial surgery.

[Using Metronidazole and Hydroxyapatite for preventing dry socket after extraction of impacted mandibular 3rd molar]

Dry socket is one of the most frequent complications after teeth extraction,especially in impacted mandibular third molars.The etilogy and prevention is not clear.This study id based on principles of clinical epidemiology.Randomized double-blind method was carried out in 549 patients to test the value of the prophylactic use of Hydroxyapatite,to test the value of the prophylactic use of Hydroxyapatite and Metronidazole,placed in the sockets of extracted impacted mandibular third molars.The results of the incidence of DS was 7.1% of Metronidazole treated sockets,and 2.1% of Hydroxyapatite treated sockets,It is concluded that Hydroxyapatite is an effective preventive factor for dry socket,The possible mechanism of Hydroxyapatite and the dry socket etiology were discussed.

[Morphological changes in tongue cancer after cryosurgery].

Tca 8113 (human tongue cancer cell line) cell transplanted tumors in nude mice were treated with cryosurgery for three freeze-thaw cycles. Tumor samples were obtained by biopsies pre- and post-cryosurgery for morphological study. The results showed intercellular adhesion damage, nuclear pyknosis, cell death, etc. One week after, the deep parts of the frozen samples were similar to that of the untreated ones. Our study indicates the change of biomembrance may be also important as of nuclei in cell death and may play an important role in the treatment of cancer by cryochemistry.

Biologic effects of freezing on tissues of the maxillofacial region.

An experimental study was done on the effects of freezing on various tissues of the maxillofacial region. After freezing, skin became necrotic, but the wound healed with a flat surface. Blood vessels showed injury of the endothelial cells and thrombosis in the veins. The internal wall of some arteries became thickened, and the lumen was narrowed. Paralysis of the facial nerve occurred immediately after freezing. Function usually recovered several weeks later. Cartilage and bone showed no change in shape after freezing, but the cells were destroyed. New cartilage and bone formation were seen in the later stages.