BACKGROUND: The proportion of patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is relatively high in China. However, these patients currently lack significant benefits from available neoadjuvant treatment options. This study aims to explore the potential application value of neoadjuvant targeted therapy by evaluating its efficacy and safety in patients with EGFR-mutant resectable lung adenocarcinoma. METHODS: A multicenter retrospective study was used to analyze the treatment effect of patients with stage IIA-IIIB EGFR-mutant lung adenocarcinoma who underwent surgical resection after receiving neoadjuvant targeted therapy from July 2019 to October 2024. RESULTS: A total of 24 patients with EGFR-mutant lung adenocarcinoma from three centers were included in this study. All patients successfully underwent surgery and achieved R0 resection of 100.0%. The objective response rate (ORR) was 83.3% (20/24) . The major pathologic response (MPR) rate was 37.5% (9/24), with 2 patients (8.3%) achieving pathological complete response (pCR). During neoadjuvant therapy, 13 out of 24 patients (54.2%) experienced adverse events of grade 1-2, with no occurrences of ≥ grade 3. The most common treatment-related adverse events were rash (n=4, 16.7%), mouth sores (n=2, 8.3%), and diarrhea (n=2, 8.3%). The median follow-up time was 33.0 months, no deaths occurred in all patients, and the overall survival (OS) rate was 100.0%. The 1-year disease-free survival (DFS) rate was 91.1%, and the 2-year DFS rate remained at 86.2%. CONCLUSIONS The application of neoadjuvant targeted therapy in patients with EGFR-mutant resectable lung adenocarcinoma is safe and feasible, and is expected to become a highly promising neoadjuvant treatment option for the patients with EGFR-mutant lung adenocarcinoma.
Humans ; ErbB Receptors/metabolism* ; Male ; Female ; Middle Aged ; Adenocarcinoma of Lung/surgery* ; Neoadjuvant Therapy ; Lung Neoplasms/surgery* ; Aged ; Retrospective Studies ; Mutation ; Adult

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment

OBJECTIVETo screen the microRNAs involved in colon cancer proliferation and to investigate the expression and regulating function of target miRNA in colon cancer.

METHODSMitochondrial transcription factor A(TFAM), which was proved to be an oncogene to colon cancer in prior study, was used as target gene. The microRNAs involved in colon cancer proliferation were screened with miRWalk 2.0 software. The expression of screened miRNAs was examined in 30 samples of colon cancer tissue, para-cancer tissue, normal colon cell strain, and 3 colon cancer strains (SW480, HT-29, and HCT116) by real-time PCR. MiR-204 presenting lowest expression was selected to further study in SW480 cells. Dual luciferase reporter assays was performed to examine the association of TFAM with miR-204. Anti-miR-204 lentivirus and miR-240 lentivirus were used to down-regulate and up-regulate miR-204 expression respectively. Change of TFAM protein expression in SW480 cells was detected by Western blotting, and change of SW480 cells proliferation was detected by MTT and BrdU assay after lentivirus transfection.

RESULTSAfter screening, the candidate miRNAs were miR-204, miR-211, miR-214, miR-381 and miR-590-3p. Expressions of miR-204, miR-211, miR-214 and miR-381 were lower, but miR-590-3p expression was higher, in colon cancer tissues than those in para-cancer tissues(all P<0.05). Meanwhile expressions of above 4 miRNAs(miR-204, miR-211, miR-214 and miR-381) were also lower, but miR-590-3p expression was higher as well, in SW480, HT-29 and HCT116 cells compared to normal colon cells(all P<0.05). Among above 4 miRNAs, miR-204 showed the lowest expression in both colon cancer tissues and cell lines. Expression of miR-204 was negatively correlated with TFAM expression in colon cancer tissues(P<0.05). Dual luciferase reporter assays revealed TFAM could be integrated with miR-204 directly, suggesting TFAM as the direct target of miR-204. After up-regulating miR-204 by lentivirus, expression of TFAM decreased and proliferation increased in SW480 cells(all P<0.05). After down-regulating miR-204 by lentivirus, expression of TFAM increased and proliferation decreased in SW480 cells(all P<0.05).

CONCLUSIONMiR-204 inhibits TFAM expression and up-regulates the proliferation of colon cancer cells SW480.

Objective To summarise the clinicopathologic features and survival of gastric cancer at different tumor locations.Methods A total of 942 adult gastric cancer patients undergoing curative gastrectomy with lymphadenectomy were recruited from the First Affiliated Hospital,Sun Yat-sen University,and examined retrospectively.In all cases,patients' age,gender,pTNM stage and survival time were identified and recorded.Results There were 208 carcinoma cases at gastroesophageal junction (GEJ,22.1％),261 fundus/body cases (27.7％),445 antrum/pylorus cases (47.2％) and 28 whole stomach cases (3.0％).Compared with fundus/body and antrum/pylorus carcinoma,GEJ carcinomas were more often seen in males,among older patients,with larger tumor size and deeper infiltrated tumors,higher stage and worse 5-year disease-free survivals.Whole stomach carcinoma had predilection in female,younger patients,and at later stages and worst 5-year disease-free survival.Conclusions Gastric carcinomas differ greatly in biologic behavior and prognosis by anatomic locations.GEJ carcinoma has independent biologic features.Whole stomach carcinoma is of the highest malignancy and worst prognosis.

Objective To screen the microRNAs involved in colon cancer proliferation and to investigate the expression and regulating function of target miRNA in colon cancer. Methods Mitochondrial transcription factor A ﹙TFAM), which was proved to be an oncogene to colon cancer in prior study, was used as target gene. The microRNAs involved in colon cancer proliferation were screened with miRWalk 2.0 software. The expression of screened miRNAs was examined in 30 samples of colon cancer tissue, para-cancer tissue, normal colon cell strain, and 3 colon cancer strains﹙SW480, HT-29, and HCT116) by real-time PCR. MiR-204 presenting lowest expression was selected to further study in SW480 cells. Dual luciferase reporter assays was performed to examine the association of TFAM with miR-204. Anti-miR-204 lentivirus and miR-240 lentivirus were used to down-regulate and up-regulate miR-204 expression respectively. Change of TFAM protein expression in SW480 cells was detected by Western blotting, and change of SW480 cells proliferation was detected by MTT and BrdU assay after lentivirus transfection. Results After screening, the candidate miRNAs were miR-204, miR-211, miR-214, miR-381 and miR-590-3p. Expressions of miR-204, miR-211, miR-214 and miR-381 were lower, but miR-590-3p expression was higher, in colon cancer tissues than those in para-cancer tissues ﹙all P<0.05). Meanwhile expressions of above 4 miRNAs﹙miR-204, miR-211, miR-214 and miR-381) were also lower, but miR-590-3p expression was higher as well, in SW480, HT-29 and HCT116 cells compared to normal colon cells ﹙all P<0.05). Among above 4 miRNAs, miR-204 showed the lowest expression in both colon cancer tissues and cell lines. Expression of miR-204 was negatively correlated with TFAM expression in colon cancer tissues﹙P<0.05). Dual luciferase reporter assays revealed TFAM could be integrated with miR-204 directly, suggesting TFAM as the direct target of miR-204. After up-regulating miR-204 by lentivirus, expression of TFAM decreased and proliferation increased in SW480 cells ﹙all P<0.05). After down-regulating miR-204 by lentivirus, expression of TFAM increased and proliferation decreased in SW480 cells (all P<0.05). Conclusion MiR-204 inhibits TFAM expression and up-regulates the proliferation of colon cancer cells SW480.

Objective To screen the microRNAs involved in colon cancer proliferation and to investigate the expression and regulating function of target miRNA in colon cancer. Methods Mitochondrial transcription factor A ﹙TFAM), which was proved to be an oncogene to colon cancer in prior study, was used as target gene. The microRNAs involved in colon cancer proliferation were screened with miRWalk 2.0 software. The expression of screened miRNAs was examined in 30 samples of colon cancer tissue, para-cancer tissue, normal colon cell strain, and 3 colon cancer strains﹙SW480, HT-29, and HCT116) by real-time PCR. MiR-204 presenting lowest expression was selected to further study in SW480 cells. Dual luciferase reporter assays was performed to examine the association of TFAM with miR-204. Anti-miR-204 lentivirus and miR-240 lentivirus were used to down-regulate and up-regulate miR-204 expression respectively. Change of TFAM protein expression in SW480 cells was detected by Western blotting, and change of SW480 cells proliferation was detected by MTT and BrdU assay after lentivirus transfection. Results After screening, the candidate miRNAs were miR-204, miR-211, miR-214, miR-381 and miR-590-3p. Expressions of miR-204, miR-211, miR-214 and miR-381 were lower, but miR-590-3p expression was higher, in colon cancer tissues than those in para-cancer tissues ﹙all P<0.05). Meanwhile expressions of above 4 miRNAs﹙miR-204, miR-211, miR-214 and miR-381) were also lower, but miR-590-3p expression was higher as well, in SW480, HT-29 and HCT116 cells compared to normal colon cells ﹙all P<0.05). Among above 4 miRNAs, miR-204 showed the lowest expression in both colon cancer tissues and cell lines. Expression of miR-204 was negatively correlated with TFAM expression in colon cancer tissues﹙P<0.05). Dual luciferase reporter assays revealed TFAM could be integrated with miR-204 directly, suggesting TFAM as the direct target of miR-204. After up-regulating miR-204 by lentivirus, expression of TFAM decreased and proliferation increased in SW480 cells ﹙all P<0.05). After down-regulating miR-204 by lentivirus, expression of TFAM increased and proliferation decreased in SW480 cells (all P<0.05). Conclusion MiR-204 inhibits TFAM expression and up-regulates the proliferation of colon cancer cells SW480.

Objective To study the feasibility, safety and clinical effects of spleen and splenic vessel-preserving distal pancreatectomy. Methods A retrospective study was performed in 26 patients undergoing distal pancreatectomy for benign or low grade malignant disease with splenectomy (n = 13) or splenic preservation (n = 13 ) at the First Hospital of Sun Yat-sen University and Guangdong General Hospital from May 2002 to April 2009. Results All 26 pancreatectomy with splenectomy or splenic preservation were performed successfully. There was no statistically significant difference between two groups in average operative time[(172±47) min vs. (157±52) min, P ＞ 0.05 ], intraoperative estimated blood loss [( 183 ± 68 ) ml vs. ( 160 ± 51 ) ml, P ＞ 0.05 ], incidence of noninfectious and infection complication and postoperative hospital stay [(10.1±2.2) d vs. ( 12. 1 ± 4. 6 ) d, P ＞ 0.05 ]. The platelet counts examined one week after operation were significantly higher in the distal pancreatectomy with splenectomy group than that in spleen-preserving group [(37.3 ± 12.8)×109/L vs. (54.7 ± 13.2) × 109/L, P＜0.05 ]. Conclusions Spleen-preserving distal pancreatectomy appears to be a feasible and safe procedure in selected cases of benign or low-grade pancreatic malignant disease necessitating a distal pancreatectomy.