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.

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.

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.

Curcumin induced apoptosis via PI3K/Akt-signalling pathways in SKOV3 cells.

Context Curcumin is widely used in China and India as a traditional herb but additional work is required to ascertain the folkloric claim of its antitumour and antioxidant activities. Objective The present study determines the antitumour effect of curcumin against SKOV3 cell growth. Materials and methods SKOV3 cells were incubated with curcumin (0, 20, 30 and 40 µM) for 72 h. The antiproliferative activity and the apoptosis rate were measured by MTT and flow cytometry. Expression of PI3K, T-Akt and p-Akt proteins was measured by western blotting. Results The administration of curcumin (0, 20, 30 and 40 µM) inhibits SKOV3 cell growth (IC50 value= 24.8 µM) and increased apoptosis (32.5 and 85.7%). The activity of SKOV3 cell invasion (98.2 and 19.4%) was also decreased by curcumin administration (p < 0.05). Results of western blot analysis confirmed that the expression of p-Akt protein was decreased by curcumin (p < 0.05). It was also found that a high dose of curcumin (40 µM) can cause stronger antitumour activity (80.4%). Conclusion Our results suggest that the curcumin induced SKOV3 apoptosis via modulation of the PI3K/Akt-signalling pathway.

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.

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 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.