Dispersion and Preparation of Nano-AlN/AA6061 Composites by Pressure Infiltration Method.

Nanomaterials play an important role in metal matrix composites (MMC). In this study, 3.0 wt.%, 6.0 wt.%, and 9.0 wt.% nano-AlN-particles-reinforced AA6061 (nano-AlN/AA6061) composites were successfully prepared by pressure infiltration technique and then hot extruded (HE) at 500 °C. The microstructural characterization of the composites after HE show that the grain structure of the Al matrix is significantly refined, varying from 2 to 20 µm down to 1 to 3 µm. Nano-AlN particles in the composites are agglomerated around the matrix, and the distribution of nano-AlN is improved after HE. The interface between AA6061 and nano-AlN is clean and smooth, without interface reaction products. The 3.0 wt.% nano-AlN/AA6061 composite shows an uppermost yield and supreme tensile strength of 333 MPa and 445 MPa, respectively. The results show that the deformation procedure of the composite is beneficial to the further dispersion of nano-AlN particles and improves the strength of nano-AlN/AA6061 composite. At the same time, the strengthening mechanism active in the composites was discussed.

Short-term dynamics of circulating tumor DNA predicting efficacy of sintilimab plus docetaxel in second-line treatment of advanced NSCLC: biomarker analysis from a single-arm, phase 2 trial.

OBJECTIVE: Robust biomarker predicting efficacy of immunotherapy is limited. Circulating tumor DNA (ctDNA) sought to effectively monitor therapeutic response as well as disease progression. This study aims to investigate predictive role of ctDNA short-term dynamic change (6 weeks postimmunotherapy) in a single-arm, phase 2 trial of sintilimab plus docetaxel for previously treated advanced non-small cell lung cancer (NSCLC) patients. METHODS: A total of 33 patients with advanced NSCLC with disease progression during or after any first-line treatment were prospectively enrolled between 2019 and 2020. Patients received sintilimab (200 mg, day 1, every 3 weeks) plus docetaxel (75 mg/m2, day 3, every 3 weeks) for 4-6 cycles, followed by maintenance therapy with sintilimab (200 mg, day 1, every 3 weeks) until disease progression or unacceptable toxic effects. Blood samples were prospectively collected at baseline, and after 2 cycles of treatment (6 weeks post-treatment). All samples were subjected to targeted next-generation sequencing with a panel of 448 cancer-related genes. The landscape of high-frequency genomic profile of baseline and 6th week was described. Major molecular characteristics in preselected genes of interest associated with response to second-line chemoimmunotherapy were analyzed. The curative effects and prognosis of patients were evaluated. RESULTS: Patients with ctDNA clearance at 6th week had decreased tumor volume, while most patients with positive ctDNA at 6th-week experienced an increase in tumor volume. Positive 6th-week ctDNA was associated with significantly shorter progression-free survival (PFS) (91 vs NR days; p<0.0001) and overall survival (47 vs 467 days; p =0.0039). Clearance of clonal mutations and none new clonal formation at 6th week were associated with longer PFS (mPFS 89 vs 266 days, p =0.003). ctDNA clearance at 6th week was an independent risk factor for progression or death (HR=100 (95% CI 4.10 to 2503.00), p=0.005). CONCLUSION: ctDNA status and ctDNA mutation clearance putatively serve as predictive biomarkers for sintilimab combined with docetaxel chemotherapy in pretreated advanced NSCLC patients.

Iodine-125 radioactive particles antagonize hyperprogressive disease following immunotherapy: A case report.

RATIONALE: Increasing evidence has shown that immune checkpoint inhibitors are associated with hyperprogressive disease (HPD). HPD usually resulted in dramatically reduced survival duration, which limited the opportunity to administer other therapies. PATIENT CONCERNS: A heavily pretreated lung adenocarcinoma patient experienced rapid progression of rib metastasis soon after immune checkpoint inhibitor -based combination therapy. DIAGNOSES: On the basis of radiographic and pathological findings, the patient was diagnosed with HPD. INTERVENTIONS: We treated the patient with iodine-125 radioactive particle implantation to the metastatic lesions in the chest wall. OUTCOMES: The metastatic lesions shrank significantly 1 month later. LESSONS: Early detection and adequate treatment are essential for prolonged survival when HPD occurs.

Esophago-tracheobronchial fistula following treatment of anlotinib in advanced squamous cell lung cancer: Two case reports.

RATIONALE: Anlotinib, a novel orally administered multitargeted tyrosine kinase inhibitor, inhibiting tumor angiogenesis and growth, significantly prolonged overall survival, and progression-free survival with a manageable safety profile as a third-line therapy among refractory advanced nonsmall cell lung cancer (NSCLC) patients in ALTER 0303 trail (NCT02388919). PATIENT CONCERNS: Two squamous cell lung cancer patients with mediastinal metastasis undergoing the treatment of anlotinib developed clinical symptom of cough, which was worse upon ingestion. DIAGNOSES: On the basis of patients' clinical symptoms and radiographic findings, they were diagnosed with acquired esophago-tracheobronchial fistula. INTERVENTIONS: We treated them with fully covered self-expandable metallic stents. OUTCOMES: The clinical symptom of cough was immediately relieved after palliative treatment. Both patients elected to discontinue anlotinib treatment. LESSONS: These 2 cases imply that a close follow-up schedule for esophago-tracheobronchial fistula should be established when squamous cell lung cancer patients with mediastinal metastasis are undergoing anlotinib therapy. Early detection and adequate treatment are essential for patient symptom relief and survival.

Risk patterns of subsequent primary cancers following esophagectomy in early-stage thoracic esophageal squamous cell cancer patients.

AIMS AND BACKGROUND: Subsequent primary cancers (SPCs) have been demonstrated to be the major causes of death among patients with thoracic esophageal squamous cell cancer (ESCC) negative for lymph node involvement. We designed this study to investigate clinical characteristics and risk patterns of SPCs following esophagectomy in patients with early-stage thoracic ESCC. METHODS: We retrospectively analyzed clinical factors in 512 patients with early-stage thoracic ESCC collected from 3 independent hospitals over a 10-year interval. RESULTS: The overall standard incidence rate (SIR) of SPCs was 3.84 (95% confidence interval 2.98-4.95). The most common SPCs were head and neck cancers, lung cancer, and stomach cancer. The risk patterns of SPCs varied across organs. A 3-phase risk pattern with a U-shaped curve between 2 rising phases was seen for head and neck cancers, while for the other cancers, the risk patterns all displayed as an approximately linear upward trend. It was further noted that sex, smoking habits, and cancer histories among first-degree relatives were 3 significant independent risk factors in the development of SPCs. CONCLUSIONS: We observed significant associations between early-stage ESCC and SPCs arising from anatomically adjacent sites. The different risk patterns of SPCs indicated that follow-up strategies should be established accordingly in different organs at different times, with particularly close follow-up for head and neck cancers in the first 5 years and beyond 15 years after diagnosis of ESCC.

Diffusion-weighted imaging in assessing pathological response of tumor in breast cancer subtype to neoadjuvant chemotherapy.

PURPOSE: To investigate the efficacy of diffusion-weighted imaging (DWI) for reflecting and predicting pathological tumor response in breast cancer subtype to neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: The retrospective study included 176 patients with breast cancer who underwent magnetic resonance imaging (MRI) examinations before and after NAC prior to surgery. The pre- and post-NAC apparent diffusion coefficient (ADC) values of tumor were measured respectively on DWI. The pathological response was classified into either a complete response (pCR) or as a noncomplete response (pNCR) to NAC with the Miller & Payne system. The relationship between the ADC value and the pathological response was assessed according to intrinsic subtypes (Luminal A, Luminal B, HER2-enriched, and triple negative) defined by immunohistochemical features. RESULTS: Multiple comparisons respectively showed that pre-NAC and post-NAC ADC were significantly different among four subtypes (P < 0.001). After the comparison between two different subtypes, the pre-NAC ADC value of the triple-negative and HER2-enriched subtypes were significantly higher than Luminal A (P < 0.001 and P < 0.001) and Luminal B subtype (P < 0.001 and P = 0.009), and the post-NAC ADC of triple-negative subtype was significantly higher than the others (P < 0.001). The pre-NAC ADC of pCRs was significantly lower than that of pNCRs only in the triple-negative subtype among four subtypes (P < 0.001), and the post-NAC ADC of pCRs was significantly higher than that of pNCRs in each subtype (P < 0.001). CONCLUSION: DWI appears to be a promising tool to determine the association of pathological response to NAC in breast cancer subtypes.

Encapsulation of an f-block metal atom/ion to enhance the stability of C20 with the I(h) symmetry.

Based on the density functional theory, the geometric and electronic structures, chemical stability, and bonding properties of the endohedral metallofullerenes, M@C20 (M = Eu(3-), Am(3-), Gd(2-), Cm(2-), Tb(-), Bk(-), Dy, Cf, Ho(+), Es(+), Er(2+), Fm(2+), Tm(3+), Md(3+), Yb(4+), No(4+), Lu(5+), and Lr(5+)), were investigated. Through encapsulation of an f-block metal atom/ion with 12 valence electrons, the bare C20 cage with the D2h point group could be stabilized to a highly symmetrical Ih structure. The calculated values of HOMO-LUMO energy gaps using the B3lYP and BHHLYP functionals ranged from 2.22 to 5.39 eV and from 3.89 to 7.95 eV, respectively. The stability of these metal-encapsulated clusters can be attributed to the 32-electron rule, where the central metal atom's orbitals strongly participated in the t2u, gu, t1u, hg, and ag valence molecular orbitals.

Diagnostic accuracy of MRI-guided percutaneous transthoracic needle biopsy of solitary pulmonary nodules.

OBJECTIVE: The purpose of our study was to evaluate the diagnostic accuracy of MRI-guided percutaneous transthoracic needle biopsy (PTNB) of solitary pulmonary nodules (SPNs). METHODS: Retrospective review of 69 patients who underwent MR-guided PTNB of SPNs was performed. Each case was reviewed for complications. The final diagnosis was established by surgical pathology of the nodule or clinical and imaging follow-up. Pneumothorax rate and diagnostic accuracy were compared between two groups according to nodule diameter (≤2 vs. >2 cm) using χ (2) chest and Fisher's exact test, respectively. RESULTS: The success rate of single puncture was 95.6 %. Twelve (17.4 %) patients had pneumothorax, with 1 (1.4 %) requiring chest tube insertion. Mild hemoptysis occurred in 7 (7.2 %) patients. All of the sample material was sufficient for histological diagnostic evaluation. Pathological analysis of biopsy specimens showed 46 malignant, 22 benign, and 1 nondiagnostic nodule. The final diagnoses were 49 malignant nodules and 20 benign nodules basing on postoperative histopathology and clinical follow-up data. One nondiagnostic sample was excluded from calculating diagnostic performance. A sensitivity, specificity, accuracy, positive predictive value, and negative predictive value in diagnosing SPNs were 95.8, 100, 97.0, 100, and 90.9 %, respectively. Pneumothorax rate, diagnostic sensitivity, and accuracy were not significantly different between the two groups (P > 0.05). CONCLUSIONS: MRI-guided PTNB is safe, feasible, and high accurate diagnostic technique for pathologic diagnosis of pulmonary nodules.

[Correlations between MRI apparent diffusion coefficient and histological grade and molecular biology of breast invasive ductal carcinoma].

OBJECTIVE: To study the correlation between the MRI apparent diffusion coefficient (ADC) value and histological grade and molecular biology of breast invasive ductal carcinoma (IDC). METHODS: This retrospective study included 125 patients with IDC verified by pathology from February 2010 to February 2013. Conventional MRI and diffusion-weighted imaging (DWI) examination were performed using a 3.0T scanner with diffusion factor of 0 and 800 s/mm(2). The region of interest (ROI) was drawn on the largest lesion and/or its two adjacent slices. The ADC value of the whole tumor was calculated as the mean ADC value. The correlation between mean ADCs and histological grade and biological factors was analyzed. RESULTS: The mean ADC of pathological grade I, II and III IDC was (1.152 ± 0.072)×10(-3) mm(2)/s, (1.102 ± 0.101)×10(-3) mm(2)/s, and (1.035 ± 0.107)×10(-3) mm(2)/s, respectively. There was a statistically significant difference among them (P = 0.003). Statistically a significant difference was observed between grade III and I (P = 0.034), grade III and II (P = 0.006), but not between grade I and II (P = 0.741). A significant correlation was observed between ADC value and pathological grade (r = -0.342, P < 0.001). The median ADC values were significantly higher in the ER-negative than in the ER-positive cases [(1.130 ± 0.115)×10(-3) mm(2)/s vs. (1.060 ± 0.089) ×10(-3) mm(2)/s, P < 0.001)], in PR-negative than in PR-positive cases [(1.121 ± 0.106)×10(-3) mm(2)/s vs. (1.055 ± 0.096) ×10(-3) mm(2)/s, P < 0.001)], and in Ki-67-negative than in Ki-67-positive cases [(1.153 ± 0.090)×10(-3) mm(2)/s vs. (1.063 ± 0.101) ×10(-3) mm(2)/s, P < 0.001]. A statistically significant correlation was observed between ADC value and expressions of ER, PR, and Ki-67 (r = -0.311, r = -0.317, r = -0.414, P < 0.001). CONCLUSION: ADC value of breast invasive ductal carcinoma is correlated with histological grade, and expression of ER, PR and Ki-67.

Value of dual-time-point FDG PET/CT for mediastinal nodal staging in non-small-cell lung cancer patients with lung comorbidity.

PURPOSE: To evaluate the efficacy of dual-time-point F-18 fluorodeoxyglucose positron emission tomography (FDG PET)/ computed tomography (CT) for mediastinal nodal staging in non-small-cell lung cancer patients with lung comorbidity. MATERIALS AND METHODS: Fifty-three pathologically proven non-small-cell lung cancer patients with pulmonary comorbidity and 49 patients as controlled group without comorbidity were enrolled. PET/CT was performed at 1-hour (whole body) post-FDG injection and repeated 2 hours (thoracic) after injection. All patients received radical surgery with system mediastinal lymph node (LN) dissection. The results of LN detection by single-time-point and dual-time-point scan were compared with the histopathologic findings. RESULTS: On a per-patient basis, in patients with pulmonary comorbidity, the sensitivity, specificity, accuracy, and positive predictive values (PPV), and negative predictive values of single-time-point scan were 87.5%, 59.5%, 67.9%, 48.3%, and 91.7%, respectively. Those values of dual-time-point scan were 93.8%, 67.6%, 75.5%, 55.6%, and 96.2%, respectively. In patients without comorbidity, dual-time-point scan was similar in those values to single-time-point. On a per-nodal station basis, the specificity, accuracy, and PPV of dual-time-point scan were better than those of single-time-point with statistically significant differences (P = 0.017, 0.002, and 0.027, respectively) in patients with pulmonary comorbidity, but the difference was not statistically significant in patients with no pulmonary comorbidity. CONCLUSIONS: Dual-time-point FDG PET/CT is more effective for mediastinal nodal staging than single-time-point in patients with pulmonary comorbidity. Dual-time-point scan was useful for diagnosis of mediastinal LN metastases in reducing the false-positive results in all patients, but improved specificity, accuracy, and PPV only in patients with pulmonary comorbidity.

Clinical applications of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in carcinoma of unknown primary.

BACKGROUND: Carcinoma of unknown primary (CUP) encompasses a heterogeneous group of tumors with varying clinical features. The management of patients of CUP remains a clinical challenge. The purpose of this study was to evaluate the clinical applications of integrated (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) information in patients with CUP, including detecting the occult primary tumor and effecting on disease therapy. METHODS: One hundred and forty-nine patients with histologically-proven metastases of CUP were included. For all patients, the conventional diagnostic work-up was unsuccessful in localizing the primary site. Whole-body PET/CT images were obtained approximately 60 minutes after intravenous injection of 350 - 425 MBq of (18)F-FDG. RESULTS: In 24.8% of patients, FDG PET/CT detected primary tumors that were not apparent after conventional workup. In this group of patients, the overall sensitivity, specificity, and accuracy rates of FDG PET/CT in detecting unknown primary tumors were 86.0%, 87.7%, and 87.2%, respectively. FDG PET/CT imaging also led to the detection of previously unrecognized metastases in 29.5% of patients. Forty-seven (31.5%, 47 of 149) patients underwent a change in therapeutic management. CONCLUSIONS: FDG PET/CT is a valuable tool in patients with CUP, because it assisted in detecting unknown primary tumors and previously unrecognized distant metastases, and optimized the management of these patients.

Relationship between primary tumor fluorodeoxyglucose uptake and nodal or distant metastases at presentation in T1 stage non-small cell lung cancer.

Many studies have shown that FDG uptake is related to prognosis of non-small cell lung cancer, and metastasis is the major cause of death due to lung cancer patients. However, the FDG uptake of primary tumor in relation to nodal or distant metastasis at presentation has not been studied directly. Newly diagnosed non-small cell lung cancer patients who accepted (18)F-FDG PET/CT staging in the nuclear medicine center of Shandong Cancer Hospital between 1 June 2004 and 1 October 2007 were retrospectively reviewed. One hundred and seven patients with clinical T1 stage and definited histologic or cytologic evidence were enrolled and analyzed. Significant differences were observed in primary tumor SUVmax for different stages (Stage Ia-IV, P=0.004), different N status (N(0)M(0) vs. N(1-3)M(0), P=0.008) and tumors absence any spread vs. presence distant metastasis (N(0)M(0) vs. M(1), P=0.000). Spearman rank analysis showed moderate correlations between SUVmax and different N or M status (r=0.369, P=0.000 for Stage Ia-IV; r=0.337, P=0.004 for N(0)M(0) vs. N(1-3)M(0); r=0.474, P=0.000 for N(0)M(0) vs. M(1); respectively). There was a statistically significant increase in the probability of metastases at presentation with each unit increase in SUVmax. (logistic regression model, OR=1.469; 95% CI, 1.175-1.836; P=0.001). These results suggest that FDG uptake is a potential indicator of metastases in small primary lesion of non-small cell lung cancer.

[Significance of dual-time-point 18F-FDG PET imaging in evaluation of hilar and mediastinal lymph node metastasis in non-small-cell lung cancer].

OBJECTIVE: To explore the diagnostic value of dual-time-point 18F-FDG PET-CT imaging in detecting hilar and mediastinal lymph node metastasis in non-small-cell lung cancer (NSCLC). METHODS: Forty-six patients with NSCLC underwent standard whole body single-time 18F-FDG PET-CT scans and a delayed imaging for the thorax alone before surgery, meanwhile, the standard uptake value (SUV) and retention index (RI) were calculated. RESULTS: A total number of 584 lymph nodes were excised in the 46 patients. Of these, 134 metastatic lymph nodes were pathologically confirmed in 31 patients. There were 189 lymph nodes detected and suspected to be metastatic by standard single-time 18 F-FDG PET-CT imaging, and 161 by dual-time-point imaging. Therefore, the sensitivity, specificity, diagnostic accuracy, positive predictive value and negative predictive value in the detection of hilar and mediastinal lymph node metastasis were 87.3%, 84.0%, 84.8%, 61.9% and 95.7% by standard single-time 18F-FDG PET-CT imaging, versus 94.8%, 92.2%, 92.8%, 78.9% and 98.1%, respectively, by dual-time-point imaging. There was a statistically significant difference in the detection of lymph node metastasis between the standard single-time imaging and dual-time-point 18F-FDG PET-CT imaging. CONCLUSION: Dual-time-point 18F-FDG PET-CT imaging is more sensitive, specific and accurate than standard single-time 18F-FDG PET-CT imaging in the detection of hilar and mediastinal lymph node metastasis, and may provide more information for diagnosis, staging and treatment of non-small cell lung cancer.

Promoter hypermethylation-mediated down-regulation of CXCL12 in human astrocytoma.

It has recently been demonstrated that CXCL12 is absent in colonic carcinoma, and hypermethylation of CXCL12 contributes to CXCL12/CXCR4 signaling in carcinoma metastasis. However, the role of CXCL12/CXCR4 axis, especially CXCL12, in the regulation of tumor invasiveness is largely still unknown. Using real-time quantitative RT-PCR assays, we observed that CXCR4 expression increased with increasing WHO grade in astrocytoma, suggesting that CXCR4 may be a marker of aggressive biological behavior of astrocytoma. Methylation of CXCL12 was detected in 34.2% (26/76) of astrocytomas by methylation-specific PCR. Epigenetic inactivation of CXCL12 was implicated mainly in low-grade astrocytomas, via DNA hypermethylation by DNMT1, -3A, and -3B; 21.1% (16/76) of the astrocytomas showed reduced or lack of CXCL12 expression, in line with epigenetic silencing of gene transcripts. However, it is interesting to note that 61.8% (47/76) of tumors, mainly high-grade astrocytomas, displayed elevated transcription of CXCL12. The expression levels of CXCL12 mRNA in glioblastomas (WHO grade IV) were significantly higher than in normal brain tissues. In summary, our data show that CXCL12 promoter hypermethylation is an early event in astrocytoma development. However, the high expressions of CXCR4 and CXCL12 in glioblastomas, the more invasive astrocytomas, suggest a different role of CXCL12/CXCR4 signaling axis in astrocytoma progression.