Single-cell RNA sequencing reveals tumor heterogeneity, microenvironment, and drug-resistance mechanisms of recurrent glioblastoma.

Glioblastomas are highly heterogeneous brain tumors. Despite the availability of standard treatment for glioblastoma multiforme (GBM), i.e., Stupp protocol, which involves surgical resection followed by radiotherapy and chemotherapy, glioblastoma remains refractory to treatment and recurrence is inevitable. Moreover, the biology of recurrent glioblastoma remains unclear. Increasing evidence has shown that intratumoral heterogeneity and the tumor microenvironment contribute to therapeutic resistance. However, the interaction between intracellular heterogeneity and drug resistance in recurrent GBMs remains controversial. The aim of this study was to map the transcriptome landscape of cancer cells and the tumor heterogeneity and tumor microenvironment in recurrent and drug-resistant GBMs at a single-cell resolution and further explore the mechanism of drug resistance of GBMs. We analyzed six tumor tissue samples from three patients with primary GBM and three patients with recurrent GBM in which recurrence and drug resistance developed after treatment with the standard Stupp protocol using single-cell RNA sequencing. Using unbiased clustering, nine major cell clusters were identified. Upregulation of the expression of stemness-related and cell-cycle-related genes was observed in recurrent GBM cells. Compared with the initial GBM tissues, recurrent GBM tissues showed a decreased proportion of microglia, consistent with previous reports. Finally, vascular endothelial growth factor A expression and the blood-brain barrier permeability were high, and the O6 -methylguanine DNA methyltransferase-related signaling pathway was activated in recurrent GBM. Our results delineate the single-cell map of recurrent glioblastoma, tumor heterogeneity, tumor microenvironment, and drug-resistance mechanisms, providing new insights into treatment strategies for recurrent glioblastomas.

Effects of MiR-210 on proliferation, apoptosis and invasion abilities of esophageal cancer cells.

PURPOSE: To investigate the effects of microRNA-210 (miRNA- 210) on the biological behaviors (proliferation and invasion) of EC109 cells of highly metastatic human esophageal cancer (EC). METHODS: The EC109 genomic DNA of human EC was used as a template to amplify the precursor sequence of miRNA-210 by polymerase chain reaction (PCR). The precursor sequence of miRNA-210 was sub-cloned into the eukaryotic expression vector pcDNA3.1(-) via double digestion by BamH I and Hind III restriction enzymes. Then the pcDNA3.1 (-)-pri-miRNA-210 vector (named as p-miRNA-210) that was constructed successfully was transiently transfected into EC109 cells of human EC in vitro. Quantitative real-time PCR (qRT-PCR) was used to detect the expression level of mature miR-210. 3-(4,5-dimethyl-2-thiazolyl)-2,5- diphenyl-2-H-tetrazolium bromide (MTT) assay and scratch method were adopted to detect the proliferation and in vitro migration of EC109 cells, and flow cytometry was performed to detect the degree of cell apoptosis. RESULTS: The eukaryotic expression vector carrying miRNA- 210 was constructed successfully. Compared with that in the blank group (Mock) and the control group (P-Blank), miRNA-210 was overexpressed in the transfected EC109 cells. The cell apoptosis was significantly increased compared with that in the control group (p<0.05); the inhibition of proliferation of EC109 cells in the p-miRNA-210 vector transfected group was remarkably elevated (p<0.05), and wound healing ability was also significantly increased (p<0.05). CONCLUSION: The overexpression of miRNA-210 can significantly inhibit the proliferation of EC109 cells of human EC and accelerate the migration ability and the rate of apoptosis, providing a potential strategy for the treatment of EC.

MiR-34a Inhibits Viability and Invasion of Human Papillomavirus-Positive Cervical Cancer Cells by Targeting E2F3 and Regulating Survivin.

OBJECTIVE: Previous studies confirmed that high-risk human papillomavirus (HR-HPV) infection is a risk factor of cervical cancer, and the infection was associated with significantly reduced miR-34a expression during carcinogenesis. However, the downstream targets of miR-34a and their roles are still not well understood. This study explored the regulative role of miR-34a on E2F3 and survivin expression and the viability and invasion of HPV-positive cervical cancer cells. METHODS: MiR-34a and survivin expression in 56 cases of HR-HPV-positive patients, 28 cases of HR-HPV-negative patients, and 28 normal cases without HR-HPV infections were measured. Human papillomavirus-18-positive HeLa cervical cancer cells and HPV-16-positive SiHa cells were used to explore the effect of miR-34a on cell viability and invasion. The molecular target of miR-34a was also explored in cervical cancer cells. RESULTS: The results showed that miR-34a overexpression could inhibit HPV-positive cancer cell viability, whereas its downregulation promoted cell viability. E2F3 is a direct target of miR-34a in HPV-positive cervical cancer cells. By targeting E2F3, miR-34a could regulate the expression of survivin. Thus, through regulating E2F3 and survivin, miR-34a could reduce the viability and invasion of HPV-positive cervical cancer cells. CONCLUSIONS: This study confirmed a novel miR-34a-E2F3-survivin axis in the tumor suppressor role of miR-34a in cervical cancer.

[Treating Radiation Peumonitis by Zlyin Huoxue Granule Combined Glucocorticoids and Antibiotics: a Clinical Observation].

OBJECTIVE: To observe the clinical effect of Ziyin Huoxue Granule (ZHG) combined glucocorticoids and antibiotics in treatment of radiation pneumonitis. METHODS: Totally 70 radiation pneumonitis patients were assigned to the treatment group and the control group according to random digit table, 35 in each group. All patients received glucocorticoids and antibiotics. Patients in the treatment group additionally took ZHG, one dose per day for 4 successive weeks. Watters clinical-radiologic-physiologic (CRP) score, Karnofsky Performance Status Scale (KPS) , and acute radiation injury classification [set by Radiation Therapy Oncology Group (RTOG)] were observed in the two groups before and after treatment. The application time for antibiotics and glucocorticoids was compared between the two groups. RESULTS: All patients completed this trial, and nobody dropped out or died. There was no statistical difference in Watters-CRP scores, KPS, or RTOG between the two groups before treatment (P > 0.05). Compared with before treatment in the same group, RTOG classification was obviously improved in the two groups (P < 0.05). Compared with the control group, Watters-CRP scores decreased, KPS increased, the application time for antibiotics and glucocorticoids was reduced (P < 0.05). The efficacy of RTOG classification was better in the treatment group than in the control group, but with no statistical difference between the two groups (P > 0.05). CONCLUSION: ZHG combined glucocorticoids and antibiotics was superior in treating radiation pneumonitis to using glucocorticoids or antibiotics alone in elevating Watters-CRP scores, shortening the application time for glucocorticoids and antibiotics, and improving patients' physical conditions.

TIFA enhances glycolysis through E2F1 and promotes the progression of glioma.

OBJECTIVE: TRAF interacting protein with forkhead associated domain (TIFA) influence progression of many cancers. However, its role in glioma remains to be explored. This study investigated the function of TIFA in glioma. METHODS: The TIFA expression in glioma and patient outcomes were analyzed using online database. Gene set enrichment analysis (GSEA) revealed related mechanisms of TIFA in glioma. TIFA's effects on glioma glycolysis and growth were assessed using in vitro and in vivo experiments. Moreover, luciferase reporter and ChIP were employed to explore the interactions among E2F1, GLUT1, HK2, and LDHA. The subcutaneous xenograft assay further elaborated the effects of TIFA in glioma. RESULTS: We found overexpressed TIFA in glioma. Moreover, the high TIFA expression was associated with poor prognosis of glioma. Furthermore, GSEA indicated that overexpressed TIFA promoted E2F1 and glycolysis. Knockdown of TIFA decreased glioma development in cell and mice. TIFA knockdown down-regulated the expression of E2F1, GLUT1, HK2, and LDHA. CONCLUSIONS: The study provides evidence that TIFA regulates E2F1 expression in glioma cells and promotes the proliferation, migration, and glycolysis. TIFA might be an advantageous therapeutic strategy against glioma.

Amelioration of Acute Radiation Dermatitis in Breast Cancer Patients by a Bioadhesive Barrier-Forming Gel (Episil): A Single-Center, Open, Parallel, Randomized, Phase I/II Controlled Trial.

Episil is a bioadhesive barrier-forming liquid gel that can relieve mucositis caused by radiotherapy (RT) and effectively relieve pain. The purpose of this trial is to compare the efficacy and safety of Episil in improving acute radiation dermatitis (ARD) in patients with breast cancer. This study included patients who met the criteria for postoperative RT for breast cancer. The primary end point was the grade of RD during treatment. A total of 102 patients were included in this study. The patients were grouped in a 2:1 ratio using the randomized number table method: 67 patients received Episil combined with conventional skin care (the Episil group), whereas the remaining 35 patients served as the control group and received conventional skin care only (the control group). According to the grading criteria of the Radiation Therapy Oncology Group (RTOG), the skin reaction rate and severity were significantly better in the Episil group than the control group (24.62%, 72.31%, 3.08, 0, 0 vs. 0, 85.71%, 14.29%, 0, 0, 0) across grades 0 to 4 (P < 0.05). The itchiness score exhibited s significant reduction in the Episil group as compared with the control group (P < 0.05). The results of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) showed that the overall health (z = -5.855, P < 0.001) and overall quality of life (z = -6.583, P < 0.001) were better in the Episil group than the control group after RT. Overall, in patients with breast cancer receiving RT, the topical application of Episil may significantly reduce the grading of ARD, alleviate patient symptoms, and improve the patient's overall quality of life.

Immunotherapy combined with antiangiogenic therapy as third- or further-line therapy for stage IV non-small cell lung cancer patients with ECOG performance status 2: A retrospective study.

BACKGROUND: Patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 2 probably cannot tolerate chemotherapy or other antitumor therapies. Some studies have reported that immunotherapy combined with antiangiogenic therapy is well-tolerated and shows good antitumor activity. However, the efficacy of this combination as a later-line therapy in patients with ECOG PS 2 is unclear. This study evaluated the effectiveness and safety of this combination strategy as third- or further-line therapy in stage IV non-small cell lung cancer (NSCLC) patients with ECOG PS 2. METHODS: In this retrospective study, patients treated with camrelizumab plus antiangiogenic therapy (bevacizumab, anlotinib, or recombinant human endostatin) were included. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), quality of life (QOL) assessed by ECOG PS, and safety were analyzed. RESULTS: Between January 10, 2019, and February 28, 2024, a total of 59 patients were included. The ORR was 35.6% (21/59) and the DCR was 86.4%. With a median follow-up of 10.5 months (range: 0.7-23.7), the median PFS was 5.5 months (95% confidence interval [CI]: 3.8-7.3) and the median OS was 10.5 months (95% CI: 11.2-13.6). QOL was improved (≥1 reduction in ECOG PS) in 39 patients (66.1%). The most common Grade 3-4 treatment-related adverse events were hepatic dysfunction (6 [10%]), hypertension (5 [8%]), and hypothyroidism (3 [5%]). There were no treatment-related deaths. CONCLUSIONS: Third- or further-line immunotherapy combined with antiangiogenic therapy is well-tolerated and shows good antitumor activity in stage IV NSCLC patients with ECOG PS 2. Future large-scale prospective studies are required to confirm the clinical benefits of this combination therapy.

A phase II study of preoperative chemotherapy with modified FOLFOX6 followed by surgery and postoperative chemoradiation in patients with localized gastric adenocarcinoma.

The optimal neoadjuvant and adjuvant treatment for gastric cancer remains controversial. We conducted a phase II study using preoperative chemotherapy with modified FOLFOX6 followed by surgical resection and postoperative chemoradiation in patients with gastric carcinoma. Preoperative chemotherapy (two or three cycles) consisted of a 2-h infusion of oxaliplatin (100 mg/m2) and folinic acid (100 mg/m2) followed by a 46-h continuous infusion of 5-fluorouracil (5-FU; 2,400 mg/m2). Surgical resection was planned 4 weeks after the last chemotherapy cycle. Patients underwent postsurgical chemoradiation, receiving a total dose of 45 Gy and 5-FU continuous infusion (350 mg/m2/day). The primary end points were feasibility, overall response rate, and R0 resectability rate after preoperative chemotherapy. The secondary end points were tolerability, treatment-associated complications, disease-free survival, and overall survival. Nineteen patients were enrolled in this study. After neoadjuvant treatment, four patients (21.1%) experienced progressive disease, six patients (31.6%) showed partial remission, and nine patients (47.3%) showed stable disease. In 15 patients (78.9%) R0 resectability could be achieved. Eleven of these patients (73.3%) were able to undergo postoperative chemoradiation. Notably, eight (72.7%) of these patients were disease free and alive at median follow-up of 60 months. Chemotherapy associated neutropenia, neutropenic fever, and anastomotic dehiscence were observed. The combination of preoperative chemotherapy and postoperative chemoradiation is feasible in a significant subset of gastric cancer patients.

DARS-AS1 modulates cell proliferation and migration of gastric cancer cells by regulating miR-330-3p/NAT10 axis.

The long noncoding RNA DARS-AS1 was aberrantly expressed and participated in several human cancer progressions, whereas whether DARS-AS1 is involved in human gastric cancer remains unclear. This study aimed to investigate the influence of DARS-AS1 on gastric cancer progression and explore the potential regulatory network of DARS-AS1/miR-330-3p/NAT10. The expression levels of DARS-AS1, miR-330-3p, and NAT10 were measured by quantitative real-time polymerase chain reaction. The CCK-8 assay and Transwell assay were used to determine the cell viability, migration, and invasion capacities, respectively. The target association between miR-330-3p and DARS-AS1 or NAT10 was confirmed using a luciferase reporter assay. In result, DARS-AS1 levels were elevated in tumor tissues and associated with shorter overall survival in patients with gastric cancer. Knockdown of DARS-AS1 could hamper cell viability, migration, and invasion in gastric cancer cells. DARS-AS1 acts as a competitive endogenous RNA to regulate the NAT10 expression by sponging miR-330-3p in gastric cancer cells. In conclusion, DARS-AS1 was elevated in gastric cancer, and DARS-AS1/miR-330-3p/NAT10 signaling offered some new horizons for predicting prognosis and a novel therapeutic method for the treatment of gastric cancer.

Combination of DCE-MRI and DWI in Predicting the Treatment Effect of Concurrent Chemoradiotherapy in Esophageal Carcinoma.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the main treatment for esophageal cancer, but the response to treatment varies from individual to individual. MR imaging methods, such as diffusion-weighted (DW) MRI and the use of dynamic contrast-enhanced (DCE) MRI, have the potential to provide additional biomarkers that could evaluate the effect of CCRT in patients with esophageal carcinoma. MATERIALS AND METHODS: Fifty-six patients with esophageal carcinoma, verified by histopathology, underwent MRI examination before and at midtreatment (4th week, radiotherapy 30-40 Gy) using the Siemens 3.0 T MR System. Parameter maps of apparent diffusion coefficient (ADC), and DCE maps of volume transfer constant (K rans), rate contrast (k ep), and extracellular fluid space (v e), were computed using a Siemens Company Multimodality Workplace (MMWP) model. Comparison of histogram parameters and their diagnostic performance was determined using the Mann-Whitney U test and receiver operating characteristic (ROC) analysis. RESULTS: 56 patient MRI scans were available for analysis at baseline and at the third week, respectively. Pretreatment K rans, pretreatment k ep, pretreatment ADC (P < 0.05), and during-treatment K rans (P < 0.05) and ΔK rans and ΔADC (P < 0.05) were significantly different after CCRT. Based on the binary logistic model, the ROC analysis demonstrated that the combined predictors demonstrated a high diagnostic performance with an AUC of 0.939. The sensitivity and specificity were 98.6% and 73.8%, respectively. CONCLUSION: The combination of DCE and DWI can be used as an early biomarker in the prediction of the effect of CCRT three weeks after treatment in esophageal carcinoma.

APJ Is Associated with Treatment Response in Gastric Cancer Patients Receiving Concurrent Chemoradiotherapy and Endostar Therapy.

BACKGROUND: Endostar combined with concurrent chemoradiotherapy (CRT) has been used in patients with gastric cancers (GCs). However, there are no reliable markers to predict the treatment response and prognosis of these patients. Apelin and its receptor (APJ) are involved in angiogenesis in tumor tissues. We aimed to study whether Apelin and Apelin receptor (APJ) tumor expression can predict the treatment response of combination therapy of endostar and CRT. MATERIALS AND METHODS: We enrolled patients with locally advanced GC receiving CRT only and CRT+endostar combination therapy. Apelin receptor (APJ) in tumor samples was determined by immunohistological staining and scored by measuring staining area and signal intensity. RESULTS: The high APJ expression has significantly higher rates of tumor invasion, local lymph node, and distant metastasis (all p < 0.001). In the CRT only group, the distribution of high and low APJ expression in patients with good and poor treatment response to CRT is not significantly different (p = 0.235). However, in the CRT+endostar group, the chance of having poor response to combined treatment is 3.645-fold higher in those having high APJ expression levels than those who have low APJ expression levels. Our prognostic analysis shows that in the CRT+endostar group, high APJ expression had significantly shorter overall survival (OS) period than those with low APJ expression (p < 0.001). Furthermore, multivariate survival analysis reveals that the APJ expression is an independent predictor for the OS period in GC patients treated with CRT+endostar. CONCLUSION: Tumor APJ can be used to predict the therapy response and prognosis in GC patients receiving CRT+endostar therapy.

Silencing of long non-coding RNA ANRIL inhibits the development of multidrug resistance in gastric cancer cells.

The development of multidrug resistance (MDR) is a crucial cause of therapy failure in gastric cancer, which results in disease recurrence and metastasis. Long non-coding RNAs (lncRNAs) have been proven to be critical in carcinogenesis and metastasis of gastric cancer. However, little is known about the roles of ANRIL (antisense non-coding RNA in the INK4 locus) in gastric cancer MDR. The aim of our study is to identify the biological function of ANRIL in gastric cancer MDR. In our results, ANRIL was highly expressed in gastric cancer tissues of cisplatin-resistant and 5-fluorouracil (5-FU)-resistant patients, and the same upregulation trends were observed in cisplatin-resistant cells (BGC823/DDP) and 5-FU-resistant cells (BGC823/5-FU). In addition, BGC823/DDP and BGC823/5-FU cells transfected with ANRIL siRNA and treated with cisplatin or 5-FU, respectively, exhibited significant lower survival rate, decreased invasion capability, and high percentage of apoptotic tumor cells. The influence of ANRIL knockdown on MDR was assessed by measuring IC50 of BGC823/DDP and BGC823/5-FU cells to cisplatin and 5-FU, the result showed that silencing ANRIL decreased the IC50 values in gastric cancer cells. Moreover, qRT-PCR and western blotting revealed that ANRIL knockdown decreased the expression of MDR1 and MRP1, both of which are MDR related genes; regression analysis showed that the expression of ANRIL positively correlated with the expression of MDR1 and MRP1, resprectively In summary, knockdown of lncRNA ANRIL in gastric cancer cells inhibits the development of MDR, suggesting an efficacious target for reversing MDR in gastric cancer therapy.

Medulloblastoma with soft-tissue and skeletal metastases in an adult: A case report.

Medulloblastoma (MB) is a highly malignant primary brain tumor, which occurs in the cerebellum or posterior cranial fossa. MB is most commonly identified in children <10 years of age. The disease is rare in adults, affecting patients aged between 30 and 50 years of age, with an incidence of 0.5 cases per 1,000,000 individuals. Extraneural metastases are reported in 7-10% of cases, most commonly involving the bones and more rarely involving the lymph nodes, visceral organs and bone marrow. The current study presents the case of a 36-year-old male who underwent a gross total resection followed by radiation therapy to the craniospinal axis for the treatment of MB. The patient subsequently developed widespread metastasis, which involved the soft tissue of the occipital bone. Subsequently, the patient was administered palliative radiotherapy and initially exhibited a good clinical response. However, the patient succumbed at 18 months post-diagnosis due to dissemination of the disease. The literature on the extraneural metastasis of MB is also reviewed in the current study.

Comparison of Gefitinib versus VMP in the combination with radiotherapy for multiple brain metastases from non-small cell lung cancer.

The purpose of this study is to compare the efficacy and safety of Gefitinib versus VMP in combination with three-dimensional conformal radiotherapy (3D-CRT) for multiple brain metastases from non-small cell lung cancer (NSCLC). A total of 73 NSCLC patients with brain metastases from January 2010 to August 2013 were randomly divided into Gefitinib group (37 patients) and VMP chemotherapy group (36 patients). Patients in VMP group received VM-26 100 mg/day by intravenous injection, from day 1 to day 3, cisplatin 25 mg/m2 by intravenous injection, from day 1 to day 3. One cycle was defined as a 21-day therapy duration, with a total of 3 cycles; 2 cycles were used for consolidation. Patients in Gefitinib group received Gefitinib orally. Both groups received 3D-CRT, DT50 Gy/25f/35d from first day and target areas were treated with whole brain radiotherapy. The results of the study are listed below: There was no significant difference in the short-term effects of the two groups (P > 0.05). Median survival time (MST) of Gefitinib was 13.3 months whereas median survival time of VMP group is 12.7 months (P < 0.05). In Gefitinib group, we did not observe any difference of the median survival time between the patients with and without mutation EGFR. Toxicity of Gefitinib groups were characterized by rash, whereas chemotherapy resulted in hematologic toxicities, which included 6 cases of III/IV leucopenia (17.6 %), 3 cases of anemia (8.8 %), and 5 cases of thrombocytopenia (14.7 %), and non-hematological toxicity which was less serious symptoms for gastrointestinal disorders, hair loss, etc. These adverse reactions can be released after symptomatic treatment. No treatment-related deaths occurred. Two patients in VMP group quit due to IV leucopenia. Both oral Gefitinib and systemic VMP chemotherapy in combination with three-dimensional conformal radiotherapy (3D-CRT) could be used to treat brain metastases from non-small cell lung cancer. There were no difference in the short-term effects of the two groups, but long-term effect of Gefitinib group was slightly better than VMP group. Moreover, Gefitinib group showed low toxicity. All together, our finding implicated that Gefitinib is an effective method for patients with brain metastases from NSCLC.

Radiation dose is associated with prognosis of small cell lung cancer with superior vena cava syndrome.

Approximately 10% of small cell lung cancer (SCLC) cases develop superior vena cava syndrome (SVCS). Many SCLC patients with SVCS have relatively limited disease, requiring curative rather than palliative treatment. Besides chemotherapy, radiotherapy is important for treating SCLC with SVCS. We retrospectively evaluated the influence of radiotherapy dose on the prognosis of 57 patients with SCLC with SVCS treated with concurrent chemoradiotherapy. The mean biological equivalent radiation dose was 71.5 Gy. We administered etoposide/cisplatin as sequential and concurrent chemotherapy. All patients received at least one cycle of concurrent chemotherapy. All patients had partial or complete response; SVCS-associated symptoms were reduced in 87.7% (50/57) of patients within 3-10 days after treatment. Radiation dose did not affect 2-year local control (74.2% vs. 80.8%). Patients who received high-dose radiation had a lower 2-year overall survival rate than those who received low-dose radiation (11.6 vs. 33%; P = 0.024). The high dose group median survival was 15.0 months (95% confidence interval [CI]: 11.2-19.0) compared with 18.7 months (95% CI: 13.9-23.6) in the low dose group. Grade 3/4 neutropenia occurred in 22/26 high dose patients (84.6%) and 21/31 low dose patients (67.7%). In the high dose group, 30.8% of patients had grade 3/4 esophagitis compared with 19.4% of low dose patients. Only 29.0% of low dose patients received < 4 cycles of chemotherapy in the first 12 weeks after treatment began compared with 46.2% of high dose patients. Concurrent chemoradiotherapy is a tolerable modality for treating stage IIIA/IIIB SCLC with SVCS. Moderate-dose radiotherapy is preferable.

OPN Polymorphism Is Related to the Chemotherapy Response and Prognosis in Advanced NSCLC.

Background. Osteopontin (OPN) is associated with prognosis of patients with non-small-cell lung cancer (NSCLC). However, little is known about the association between OPN gene polymorphism and the chemotherapy response in NSCLC patients. Methods. A total of 497 patients with inoperable advanced stage of NSCLC (stages III B and IV NSCLC) were enrolled. All patients had received platinum-based chemotherapy. OPN gene polymorphisms at 156 GG/G, 443 C/T, and -66T/G were determined. Results. The genotypes and allele frequency of -443C>T were significantly different between the responders and nonresponders. Responders had a markedly higher frequency of -443TT genotype than responders (40.71% versus 19.09%, P < 0.001). With CC as reference, the TT genotype carriers had a higher chance to be well responders (adjusted OR = 4.43, 95% CI: 2.60-7.53, adjusted P < 0.001). The median overall survival time for patients with -443CC, -443CT, and -443TT genotype carriers was significantly different. Multivariate Cox proportional hazards regression models showed that OPN -443C>T gene polymorphisms were closely correlated to poor NSCLC prognosis. Conclusion. OPN -443C>T gene polymorphism may be used as a molecular marker to predict the treatment response to chemotherapy in advanced NSCLC patients.

MicroRNA-182 modulates chemosensitivity of human non-small cell lung cancer to cisplatin by targeting PDCD4.

BACKGROUND: Overexpression of microRNA-182 (miR-182) is found in various human cancers, including non-small cell lung cancer (NSCLC). Our aim is to investigate the association of miR-182 expression with the sensitivity of NSCLC to cisplatin. METHODS: TaqMan RT-PCR or Western blot assay was performed to detect the expression of mature miR-182 and programmed cell death 4 (PDCD4) protein. miR-182 and (or) PDCD4 depleted cell lines were generated using miR-182 inhibitor and (or) siRNA. The viabilities of treated cells were analyzed using MTT assay. RESULTS: The expression level of miR-182 in A549 cell line was significantly higher than that in NHBE cell line (p < 0.01). Transfection of miR-182 inhibitor induced sensitivity of A549 cells to cisplatin. A549 cells transfected with PDCD4 siRNA became more resistant to cisplatin therapy. We found an increase PDCD4 protein level following the transfection of miR-182 inhibitor using Western blot analysis. In addition, the enhanced growth-inhibitory effect by miR-182 inhibitor was weakened after the addition of PDCD4 siRNA. CONCLUSIONS: The results of the present study demonstrated that overexpression of miR-182 may involve in chemoresistance of NSCLC cells to cisplatin by down-regulating PDCD4. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1793467320130186.

A phase II trial of post-operative chemoradiotherapy for completely resected gastric cancer with D2 lymphadenectomy.

The optimal post-operative adjuvant treatment for completely resected gastric cancer with D2 lymphadenectomy remains controversial. The present study was a phase II trial on post-operative chemoradiotherapy in 30 patients with gastric cancer. Patients with stage II to IV (M0) gastric cancer received two cycles of chemotherapy prior to and following chemoradiotherapy. The chemotherapy consisted of a 2-h infusion of oxaliplatin (100 mg/m2) and folinic acid (100 mg/m2), which was followed by a 46-h continuous infusion of 5-fluorouracil (5-FU; 2,400 mg/m2) through a portable pump, repeated every 3 weeks. The chemoradiotherapy consisted of 45 Gy of radiotherapy for 5 weeks and 5-FU continuous infusion (350 mg/m2/day). In total, 30 patients were enrolled in this study. All patients underwent the chemoradiotherapy treatment as planned. A total of 10 (33.3%) patients relapsed; two (6.7%) locoregional relapses and mediastinum metastases, four (13.3%) peritoneal relapses, and four (13.3%) distant metastases. The three-year overall survival and disease-free survival rates were 72.7 and 65%, respectively. The toxicities of chemotherapy and radiotherapy, consisting of neutropenia, nausea and hand-foot syndrome, were observed. In conclusion, post-operative chemoradiotherapy following complete resection of gastric cancer with D2 lymphadenectomy is feasible in a significant subset of patients.

High p53 and MAP1 light chain 3A co-expression predicts poor prognosis in patients with esophageal squamous cell carcinoma.

p53 and microtubule-associated protein 1 light chain 3A (LC3A) are regulators of apoptosis and autophagy and are expressed at high levels in a number of human tumors. The purpose of the current study was to evaluate the clinicopathological and prognostic significance of p53 and LC3A expression levels in esophageal squamous cell carcinomas (ESCCs). p53 and LC3A expression levels were measured by immunohistochemistry in 114 patients with stage II/III (Tany N+M0 or T3,4 Nany M0) ESCCs treated with surgery followed by adjuvant concurrent chemoradiotherapy. The overexpression of p53 and LC3A was observed in 57 and 54% of ESCC samples, respectively. p53 staining was nuclear and LC3A was localized to the cytoplasm of tumor cells. p53 overexpression was more frequently observed in ESCCs with positive lymph nodes (P=0.017). Patients with ESCCs overexpressing p53 and LC3A were associated with a lower 5­year overall survival rate than those with low p53 and LC3A expression (18.0 vs. 54.4%; P=0.001). Univariate and multivariate analyses revealed that the overexpression of p53 or LC3A was not associated with poor patient outcome (P>0.05). However, patients with high levels of p53 and LC3A co-expression had poor clinical prognoses (P=0.027). Thus, p53 and LC3A co-expression is an independent prognostic marker for patients with ESCC.