Long-term, 13-year survival after immune cell therapy combined with chemotherapy for extensive-stage small-cell lung cancer: a case report.

While the incidence of small-cell lung cancer is low, it has a poor prognosis. Patients with extensive small-cell lung cancer account for about 70% of all cases of small-cell lung cancer, with a median overall survival duration of 8-13 months and a 5-year overall survival rate of only 1%-5%. Herein, we report small-cell lung cancer diagnosed by bronchoscopic biopsy in an adult male patient in 2011. The patient had a clinical stage of cT2N2M1 and stage IV disease (i.e., extensive small-cell lung cancer). Still, he survived for 13 years through a combination of chemotherapy, radiotherapy, and cytokine-induced killer (CIK) immunocell thera. Comprehensive tumor markers, lymphocyte subsets, and lung CT images were obtained through long-term follow-up. After 12 cycles of chemotherapy (CE/IP regimen) and 5940cgy/33f radiotherapy, we found that the patient was in an immunosuppressive state, so the patient was given CIK cell therapy combined with chemotherapy. After 2 years of immunocell-combined chemotherapy, there were no significant changes in the primary lesion or other adverse events. In the 13 years since the patient's initial diagnosis, we monitored the changes in the patient's indicators such as CEA, NSE, CD4/CD8 ratio, and CD3+CD4+ lymphocytes, suggesting that these may be the factors worth evaluating regarding the patient's immune status and the effectiveness of combination therapy. In this case, CIK cell immunotherapy combined with chemotherapy was applied to control tumor progression. With a good prognosis, we concluded that CIK cell immunotherapy combined with chemotherapy can prolong patient survival in cases of extensive small-cell lung cancer, and the advantages of combined therapy are reflected in improving the body's immune capacity and enhancing the killing effect of immune cells.

Extracellular Vesicle Preparation and Analysis: A State-of-the-Art Review.

In recent decades, research on Extracellular Vesicles (EVs) has gained prominence in the life sciences due to their critical roles in both health and disease states, offering promising applications in disease diagnosis, drug delivery, and therapy. However, their inherent heterogeneity and complex origins pose significant challenges to their preparation, analysis, and subsequent clinical application. This review is structured to provide an overview of the biogenesis, composition, and various sources of EVs, thereby laying the groundwork for a detailed discussion of contemporary techniques for their preparation and analysis. Particular focus is given to state-of-the-art technologies that employ both microfluidic and non-microfluidic platforms for EV processing. Furthermore, this discourse extends into innovative approaches that incorporate artificial intelligence and cutting-edge electrochemical sensors, with a particular emphasis on single EV analysis. This review proposes current challenges and outlines prospective avenues for future research. The objective is to motivate researchers to innovate and expand methods for the preparation and analysis of EVs, fully unlocking their biomedical potential.

The Aroma Fingerprints and Discrimination Analysis of Shiitake Mushrooms from Three Different Drying Conditions by GC-IMS, GC-MS and DSA.

The aroma fingerprints and discrimination analysis of shiitake mushrooms under different drying conditions were performed by GC-IMS, GC-MS, and descriptive sensory analysis (DSA) with advanced chemometric methods. Three samples (A, B, and C) were treated with varied drying degree and rate. The sample A and C were at the same drying degree and the sample B and C were at the same drying rate. The GC-IMS volatile fingerprints, including the three-dimensional topographic map, topographic map, and gallery plot, showed that 29 compounds showed higher signal intensities in sample B. Moreover, 28 volatile compounds were identified by HS-SPME-GC-MS and only 8 compounds were ever detected by GC-IMS. The sample B not only had more varieties of volatile compounds, but also showed significant higher contents than sample A and C, especially C8 compounds (p < 0.05). Additionally, sample B showed the highest intensity in mushroom-like, chocolate-like, caramel, sweat, seasoning-like, and cooked potato-like odors by DSA. PCA, fingerprint similarity analysis (FSA) and PLSR further demonstrated that the sample B was different from sample A and C. These results revealed that samples with different drying degree were different and drying degree exerted more influence on the volatile flavor quality than the drying rate. This study will provide a foundation and establish a set of comprehensive and objective methods for further flavor analysis.

Dexmedetomidine protects PC12 cells from oxidative damage through regulation of miR-199a/HIF-1α.

Background: Although dexmedetomidine (Dex) has a significant neuroprotective effect in various nerve-damage models, the exact mechanism of which Dex protects cells from oxidative damage is not fully clear. This article recommended the protective effect of Dex on oxidative damage in PC12 cells.Methods: The PC12 cells were incubated by hydrogen peroxide (H2O2) for 24 h and pre-treated by Dex for 30 min. Cell viability, apoptosis, HIF-1α expression and ROS level were detected by CCK-8, apoptosis assay, Western blot and ROS assay, respectively. The miR-199a expression was tested by qRT-PCR. Targeting relationship between miR-199a and HIF-1α was performed by dual luciferase activity assay. The activation of PI3K/AKT/mTOR and Wnt/ß-catenin pathways was tested by western blot.Results: Dex attenuated H2O2-induced oxidative damage, including the decline of cell viability, the raise of apoptosis and the generation of ROS in PC12 cells by down-regulating miR-199a expression. Moreover, Dex up-regulated HIF-1α expression via decreasing miR-199a level in PC12 cells and miR-199a targeted the 3'-UTR of HIF-1α. In addition, Dex activated PI3K/AKT/mTOR and Wnt/ß-catenin pathways by declining miR-199a level.Conclusions: This article illustrated the protective effect of Dex on oxidative damage in PC12 cells. Furthermore, Dex prevented PC12 cells from oxidative injury through the regulation of miR-199a/HIF-1α.

miR-641 Functions as a Tumor Suppressor by Targeting MDM2 in Human Lung Cancer.

Lung cancer is the leading cause of deaths due to cancer. Studies suggest an important role of microRNAs (miRNAs) in a variety of cancers, including lung cancer. In the present study, we evaluated the role of miR-641 in human lung cancer A549 cells. Quantitative RT-PCR and Western blot were used to measure mRNA and protein expression, respectively. Cell viability and cell apoptosis were respectively measured by MTT assay and flow cytometry. In addition, luciferase activity assay was used to identify the target of miR-641. The expression of miR-641 was downregulated in lung cancer tissues and lung cancer cell lines (p < 0.05 or p < 0.01). Overexpression of miR-641 significantly inhibited proliferation and induced apoptosis of lung cancer cells (p < 0.05, p < 0.01, or p < 0.001). MDM2 was identified as a direct target of miR-641. Overexpression of miR-641 decreased the expression of MDM2 and increased the expression of p53 in lung cancer cells.

Function of miR-152 as a Tumor Suppressor in Human Breast Cancer by Targeting PIK3CA.

miR-152, as a tumor suppressor, has been reported to be downregulated in a number of cancer cell lines and tumor tissues, including breast cancer. This study aimed to investigate the role of miR-152 in human breast cancer and its underlying mechanisms. Human breast cancer cell line HCC1806 was transfected with hsa-miR-152-3p mimic, inhibitor, or scrambled negative controls. The efficiency of miR-152-3p transfection was evaluated by quantitative real-time PCR, and the effects on cell viability and apoptosis as well as on the PI3K/AKT signaling pathway were investigated by MTT assay, flow cytometry, and Western blot analysis, respectively. The binding effect of miR-152-3p on PIK3CA 3'-UTR was also investigated. The results suggested that miR-152-3p mimic transfection inhibited cell viability while inducing apoptosis of HCC1806 cells. Furthermore, miR-152-3p negatively regulated PIK3CA expression via binding to the 3'-UTR of PIK3CA and decreased the phosphorylation levels of AKT (Ser473) and RPS6 (Ser235/236) in HCC1806 cells. miR-152-3p inhibitor transfection showed the opposite effects. In conclusion, miR-152-3p might serve as a tumor suppressor in human breast cancer cells via negatively regulating PIK3CA expression to inhibit the activation of AKT and RPS6, leading to suppression of HCC1806 cell proliferation.

Complete sequence of an esophageal carcinoma inbred Sprague-Dawley rat model mitochondrial genome.

The Sprague-Dawley rat strain is a common used model for esophageal carcinoma disease study. We sequenced this rat strain mitochondrial genome for the first time. Its mitogenome was 16,312 bp and coding 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes. A total of 96 SNPs were examined when compared to reference BN sequence.

Intraoperative radiation therapy delivered prior to lumpectomy for early-stage breast cancer: a single institution study.

OBJECTIVE: To evaluate the safety, cosmesis, and clinical outcome of intraoperative electron radiation therapy (IOERT) delivered prior to lumpectomy for early-stage breast cancer. METHODS: From December 2008 to March 2012, 75 breast cancer patients (ages 34-66 years) were treated with IOERT during breast conservative surgery. IOERT was delivered using a mobile linear accelerator. Suitable energy and applicator size were chosen to ensure coverage of the tumor with anterior and posterior margins of 1 cm and lateral margins of 2 cm. Patients with sentinel node metastases or younger than 40 years received 8 Gy as boost followed by post-operative external beam radiation therapy of 50 Gy/25F; the others had 15 Gy, prescribed to the 90% isodose depth. Adjuvant treatment consisted of chemotherapy (55 patients), hormonal therapy (59 patients), or combined chemotherapy and hormonal therapy (41 patients). The safety, cosmesis, and short-term outcome were evaluated. RESULTS: Median follow-up was 54 months (range: 30-66 months). Two (2.7%) patients developed post-surgical hematoma. Six (8.0%) patients developed mild breast fibrosis. Eight (10.7%) patients suffered from local pain. One (1.2%) patient experienced a post-operative infection. Sixteen (21.3%) patients developed Grade 1 pulmonary fibrosis. Forty-three (57.3%) patients had an excellent cosmetic result and 23 (30.7%) had a good cosmetic result. Three patients had an ipsilateral breast recurrence, with an actual 3-year local recurrence rate of 4.0%. One patient had an ipsilateral axillary recurrence, resulting in a 3-year regional recurrence rate of 1.3%. No distant metastases or deaths were observed. The 3-year disease free survival was 94.6%. CONCLUSIONS: Intraoperative electron radiation therapy delivered prior to lumpectomy is safe and feasible for selected patients with early-stage breast cancer. Early side effects, cosmesis and short-term efficacy are acceptable, but a longer follow-up is needed for evaluation of late side effects and long-term outcome.

An updated meta-analysis of the association between ADIPOQ rs2241766 polymorphism and colorectal cancer.

Adiponectin (ADIPOQ) is a cytokine produced by adipose tissue involved in carcinogenesis. ADIPOQ SNP rs2241766 has been extensively studied in colorectal cancer (CRC) community with contentious and conflicting conclusions. The objective of this study was to comprehensively assess the association between SNP rs2241766 and CRC risk. PubMed, Embase, CNKI, as well as the references of the retrieved articles were searched to identify the eligible studies for this meta-analysis. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the association. We also examined the heterogeneity and publication bias and performed sensitivity analyses. Seven studies with 2,414 cases and 2,796 controls together did not show any significant association between SNP rs2241766 and CRC risk. Subgroup analyses by ethnicity and sample size also failed to provide statistically significant evidence. This meta-analysis demonstrates that ADIPOQ SNP rs2241766 may not represent as an effect modifier for the risk of CRC.

Overexpression of ZEB1 associated with metastasis and invasion in patients with gastric carcinoma.

The aim of this study was to investigate the expression of ZEB1 in gastric carcinoma, its correlation with the clinicopathology of gastric carcinoma, and the role of ZEB1 in invasion and metastasis in gastric carcinoma. ZEB1 expression was analyzed by immunohistochemistry and Western blot in 45 gastric carcinoma tissue samples that contained the adjacent gastric mucosa. The correlation between ZEB1 expression, the occurrence and development of gastric cancer, and clinical pathology was investigated. ZEB1 expression in the human gastric carcinoma cell line AGS was downregulated by RNA interference, and changes in ZEB1 expression corresponded with changes in the invasive and metastatic ability of AGS cells. Immunohistochemistry revealed that ZEB1 protein expression in gastric carcinoma tissues was significantly higher than in normal gastric mucosa tissues (p < 0.001). A lower degree of differentiation of gastric cancer (p = 0.009), a higher TNM (tumor, node, and metastasis) stage (p = 0.010), and a larger scope of invasion were correlated with higher expression of ZEB1 (p = 0.041, 0.002). However, the expression of ZEB1 in gastric carcinoma tissue was independent of gender, age, and tumor size (p > 0.05). Western blot results also showed that ZEB1 protein expression was significantly higher in gastric carcinoma tissue than in the adjacent normal gastric mucosa tissue (p = 0.008). A lower degree of differentiation of the gastric carcinoma correlated with a higher TNM stage, and a larger scope of invasion correlated with increased ZEB1 expression (p = 0.023). Transfection of ZEB1 siRNA in AGS cells significantly decreased the expression level of ZEB1 protein (p = 0.035). Furthermore, the number of cells that could pass through the Transwell chamber was significantly lower in the transfected group than in the non-transfected control group (p = 0.039), indicating that the suppression of ZEB1 expression could significantly reduce the invasive and metastatic ability of AGS cells (p = 0.005). Concluding, in gastric carcinoma tissue, overexpression of ZEB1 may be related to the occurrence and development as well as invasion and metastasis of gastric carcinoma.

RKIP expression associated with gastric cancer cell invasion and metastasis.

The purpose of this study was to analyze Raf kinase inhibitor protein (RKIP) expression in gastric cancer tissue, its correlation with gastric cancer clinical pathology, and its role in gastric cancer invasion and metastasis in order to provide experimental evidence for the potential biological therapy of this disease. Both immunohistochemistry and western blot analyses were used to test for RKIP expression in 55 cases of gastric cancer tissue and the adjacent gastric mucous membrane tissue. The correlations of RKIP expression with the onset, development, and clinical pathology of gastric cancer were analyzed. After transiently transfecting the human gastric cancer cell line MKN45 with a eukaryotic expression vector containing the full length RKIP cDNA, the changes in MKN45 cell invasiveness and metastatic ability were studied. Immunohistochemistry and western blot results revealed that the quantity of RKIP protein expressed in the gastric cancer tissues was significantly lower than that of the adjacent normal gastric mucous membrane tissues (p < 0.05). The quantity of RKIP protein expression was reduced (p < 0.05) as the gastric cancer cells' differentiation decreased, the TNM stage increased, and the extent of invasion expanded. However, the expression of RKIP in the gastric cancer tissues was not associated with the patients' age or gender (p > 0.05). By overexpressing RKIP in the human gastric cancer cell line MKN45 and through the use of a Transwell invasion chamber, we determined that RKIP overexpression significantly reduced both the invasiveness and metastatic ability of MKN45 cells (p < 0.05). Low or absent RKIP expression may be associated with the onset and development of gastric cancer and its ability to invade and metastasize.

Intraoperative radiotherapy in patients with breast cancer treated by breast-conserving therapy.

OBJECTIVE: To assess the safety, cosmetic effects, and clinical efficacy of breast-conserving surgery combined with intraoperative radiation therapy for the treatment of Chinese patients with breast cancer. METHODS: Breast-conserving surgery combined with intraoperative radiation therapy was performed in 64 breast cancer patients. The postoperative short-term efficacy, safety, and cosmetic effects were assessed. RESULTS: Of the 64 patients, 1 case (1.6%) had local recurrence one year later, 7 cases (10.9%) had grade I postoperative radiation-induced lung injury, 10 cases (15.6%) had local hardening at the surgical sites, 8 cases (12.5 %) had changes in skin color, and 8 cases (12.5%) had pain at the surgical sites. Excellent or good levels of cosmetic effects were achieved in 95.3% of the patients. CONCLUSIONS: The application of intraoperative radiation therapy with breast-conserving surgery can yield satisfactory short-term curative efficacy, a high level of clinical safety, and good cosmetic effects.

Clinical value of using ultrasound to assess calcification patterns in thyroid nodules.

BACKGROUND: Differentiating between benign and malignant thyroid nodules is important for providing appropriate treatment. In the present study we examined the clinical usefulness of ultrasound in examining calcification patterns in thyroid nodules, and thus predict malignancy. METHODS: The records of 1,498 Chinese patients who underwent thyroidectomy for nodular thyroid disease were retrospectively examined. All patients underwent thyroid ultrasound within 1 month before surgery. Calcification patterns in thyroid nodules were examined, and tissue samples were analyzed to determine a pathological diagnosis. Calcifications were defined as macrocalcifications, microcalcifications, rim calcifications, or isolated calcifications. RESULTS: A total of 2,122 thyroid nodules were examined, and 259 nodules (12.2%) were found to be malignant. Papillary carcinoma accounted for 85.3% of all malignancies. The majority of benign lesions were nodular goiters. Calcification was detected in 49.6% of malignant nodules and 15.7% of benign nodules. Microcalcifications were significantly more common in malignant nodules as compared to benign nodules (33.7 vs. 6.4%; P < 0.001). The sensitivity and specificity of microcalcifications for predicting malignancy were 33.7 and 93.6%, respectively, while the positive and negative likelihood ratios were 42.0 and 91.1%, respectively. CONCLUSIONS: Calcifications, as detected by ultrasonography, are evident in benign and malignant thyroid nodules. Although microcalcifications are more common in malignant thyroid nodules than in benign ones, the clinical value of using the presence of microcalcifications alone for predicting malignancy is limited.

[Predictive value of sonographic features in preoperative evaluation of malignant thyroid nodules].

OBJECTIVE: To retrospectively evaluate the diagnostic accuracy of ultrasonographic (US) features for the pre-operative differentiation of benign and malignant thyroid nodules by using pathological diagnosis as the reference standard. METHODS: A total of 1501 patients with 2123 thyroid nodules (1864 malignant, 259 benign) diagnosed intra-operatively and undergoing pre-operative ultrasonography at our hospital were recruited. The following characteristics of US images were evaluated: nodule size, shape, margin, echotexture, echogenicity, presence and type of calcification, blood flow inside or around nodules and the presence of ipsilateral cervical lymphadenectasis. RESULTS: (1) The risk of malignancy was higher in a solitary nodule than in a non-solitary nodule [16.7% (109/653) vs 10.2% (150/1470), P=0.000]. The mean diameter of benign nodules was larger than that of malignant nodules [(2.4±1.4) vs (2.1±1.9) cm, P=0.009]. (2) Microcalcification, irregular shape, ill-defined border, solid and hypoechogenicity were more common in malignant nodules. Irregular shape had the highest sensitivity and positive predictive value while microcalcification had the highest diagnostic accuracy. (3) Nodules with a rich blood flow inside tended to have a higher risk of malignancy. The distribution pattern of blood flow around the nodules was not associated with the differentiation of benign and malignant thyroid nodules. Nodules with the presence of ipsilateral cervical lymphadenectasis had a higher risk of malignancy than those without lymphadenectasis [28.3% (80/283) vs 9.6% (92/963), P<0.01]. (4) If microcalcification, irregular shape, ill-defined border, solid, hypoechogenicity and the presence of ipsilateral cervical lymphadenectasis were treated as the characteristics of malignancy, a higher frequency of these characteristics was correlated with a higher risk of malignancy. CONCLUSION: Despite a lack of specific US imaging characteristics in malignant thyroid nodules, microcalcification and irregular shape appear closely correlated with malignancy. A combined use of conventional US characteristics may improve the accuracy of differential diagnosis.

[Effects of neoadjuvant chemotherapy of docetaxel combined with and epirubicin or pirarubicin on breast cancer: clinical analysis of 160 cases].

OBJECTIVE: To evaluate the effects and toxicity of the neoadjuvant chemotherapy of docetaxel combined with epirubicin or pirarubicin on breast cancer, and to investigate the influencing factors of the response to neoadjuvant chemotherapy. METHODS: 160 patients with stage II/III breast cancer, all females, aged 47 (22-66), were treated with docetaxel plus epirubicin or pirarubicin with 3 weeks as a cycle. Two to six cycles of treatment were given before surgery. The clinical efficacy and toxicity of the treatment were evaluated, and the correlation between the influencing factors and the clinical parameters with treatment response was analyzed. RESULTS: The clinical response rate (RR) was 90% (144/160), the complete response (CR) rate was 26% (41/160), the partial response (PR) rate was 64% (103/160). The stable disease (SD) rate was 8% (13/160). The progress disease (PD) rate was 2% (3/160), the pathologically complete remission (pCR) rate was 7% (11/160), and the tumor-pathological complete response (tpCR) rate was 2% (1.3/160). Univariate analysis showed that the tumor size, clinical stage, triple negative phenotype might be the meaningful parameters influencing the clinical response. The patients with smaller tumor size, low stage tumor, and being triple-negative were more likely to achieve CR (P = 0.0371, 0.0013, and 0.0019 respectively). Age, histological grading, ER/PR ratio, Her-2 status did not significantly influence the early response. Multivariate analysis showed that the disease stage might be the meaningful factors for better response (P = 0.0030). The major toxic reactions of the therapy included neutropenia, alopecia, nausea, and vomiting. CONCLUSION: The combination neoadjuvant chemotherapy with docetaxel and epirubicin or pirarubicin is an effective method to treat breast cancer with tolerable toxicity. The meaningful parameter influencing the early response is clinical stage.

[Prevention and management of frequent complications after endovascular repair of infrarenal abdominal aortic aneurysm].

OBJECTIVE: To prevent and manage frequent complications after endovascular repair of infrarenal abdominal aortic aneurysm (AAA). METHODS: The data of 71 cases of infrarenal abdominal aortic aneurysm (AAA) treated by endovascular repair were analysed retrospectively. The reasons, managements, results and prognosis of frequent complications were investigated. RESULTS: Seventy-one cases of infrarenal AAA were treated by endovascular repair with 100% success rate. There was no surgical conversion to open aneurysm repair. There were 8 cases of primary endoleak, 1 case of nervous complication and acute thrombosis. An average follow-up period was 26 +/- 5 months. Three persistent endoleaks and 4 secondary endoleaks were found during the follow-up period. The endoleak rate was 9.8% (7/71) within 1 month postoperatively and mortality rate was 1.3% (1/71). Total mortality rate was 4.2% (3/71). Two patients died from acute myocardial infarction and one from acute heart failure. CONCLUSIONS: Endovascular treatment of abdominal aortic aneurysm is technically feasible and can effectively exclude aortic aneurysms from the circulation. Endoleak is a chief complication after endovascular repair of infrarenal AAA.Additional procedures and follow up are very important. Endoleak with enlarged aneurysm should be treated actively.

[Endovascular treatment for abdominal aortic aneurysm, a primary study].

OBJECTIVE: To summarize the initial experience of endoluminal stent-grafting in the treatment of abdominal aortic aneurysm (AAA). METHODS: Stent-graft of proper shape and size was selected according to the morphology of AAA and was inserted into the lumen of abdominal aortic aneurysm through femoral artery to reconstruct the blood flow under X-ray flouroscopy among 34 cases. Data on complications and morphological changes were obtained according to a strict follow-up plan. RESULTS: The stent-grafting procedure was technically successful in all 34 patients. None of them required open repair. Five patients (14.7%) suffered from primary endoleaks after stent-graft deployment and 1 patient suffered from paraplegia and acute graft thrombosis. No other complications (kidney infarction, limbs and colon ischemia, etc) were found. The average follow-up time was 21 +/- 4.7 months. Perioperative death rate was 0% and total death rate was 3%. Two cases with primary endoleak developed into lasting endoleak during the follow-up period with a rate of late endoleak (> 30 days) of 11.7%. Secondary endoleak was found in 2 cases. One case with limb stent disconnection accepted secondary intervention. The mean max aneurysm diameter in cases without endoleak decreased significantly 6 months to 2 years after operation (P < 0.01). The aneurysm in two cases with secondary type I endoleak increased and one of them underwent secondary intraluminal treatment. CONCLUSION: Endovascular technique is a reliable method of treating AAA with micro-trauma. Endoleak is the main complication of this technique. Follow-up is an important component of the treatment plan. The aim of endoluminal repair is to completely neglect the aneurysmal lumen and prevent the aneurysm from increasing during follow-up.