Research progress and applications of epigenetic biomarkers in cancer.

Epigenetic changes are heritable changes in gene expression without changes in the nucleotide sequence of genes. Epigenetic changes play an important role in the development of cancer and in the process of malignancy metastasis. Previous studies have shown that abnormal epigenetic changes can be used as biomarkers for disease status and disease prediction. The reversibility and controllability of epigenetic modification changes also provide new strategies for early disease prevention and treatment. In addition, corresponding drug development has also reached the clinical stage. In this paper, we will discuss the recent progress and application status of tumor epigenetic biomarkers from three perspectives: DNA methylation, non-coding RNA, and histone modification, in order to provide new opportunities for additional tumor research and applications.

Advances in Drug Therapy for Metastatic Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a notably poor prognosis. A large number of patients with PDAC develop metastases before they are diagnosed with metastatic pancreatic cancer (mPDAC). For mPDAC, FOLFIRINOX or gemcitabine plus nab-paclitaxel are the current first-line treatments. It is important to note, however, that many patients will fail chemotherapy because of drug resistance. ​Heterogeneous tumors and complex tumor microenvironments are key factors. As a result, clinical researchers are exploring a variety of alternative treatment modalities. Current understanding of the molecular signature and immune landscape of PDAC has motivated the emergence of different targeted and immune-based therapeutic approaches, some of which have shown promising results. The purpose of this review is to discuss the new targets and new drugs for mPDAC in terms of specific pathogenic factors such as metabolic vulnerability, DNA damage repair system, tumor microenvironment and immune system, in order to identify potential vulnerabilities in mPDAC patients and hopefully improve the prognosis of mPDAC patients.

Ferroptosis: New Strategies and Ideas for the Treatment of Pancreatic Ductal Adenocarcinoma.

Pancreatic cancer is a malignancy that affects the digestive tract and has a low 5-year survival rate of lower than 15%. Owing to its genetic mutation and metabolic complexity, pancreatic cancer is difficult to treat with surgical resection, radiotherapy, and chemotherapy. The predominant modality of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), primarily attributed to mutations in KRAS gene. Ferroptosis, an iron-mediated reactive oxygen species (ROS)-elevated nonapoptotic cell death caused by lipid peroxidation, is distinct from any other known type of cell death. Ferroptosis is closely related to the occurrence and progression of different types of cancers, including PDAC. Previous research has demonstrated that ferroptosis not only triggers cell death in PDAC and hampers tumor growth but also enhances the effectiveness of antitumor medications. In our review, we mainly focus on the core mechanism of ferroptosis, reveal its interrelationship with PDAC, and illustrate the progress of ferroptosis in different treatment methods of PDAC.

Changes in cortical activation during upright stance in individuals with chronic low back pain: An fNIRS study.

Introduction: Postural control deficits are a potential cause of persistent and recurrent pain in patients with chronic low back pain (CLBP). Although some studies have confirmed that the dorsolateral prefrontal cortex (DLPFC) contributes to pain regulation in CLBP, its role in the postural control of patients with CLBP remains unclear. Therefore, this study aimed to investigate the DLPFC activation of patients with CLBP and healthy controls under different upright stance task conditions. Methods: Twenty patients with CLBP (26.50 ± 2.48 years) and 20 healthy controls (25.75 ± 3.57 years) performed upright stance tasks under three conditions: Task-1 was static balance with eyes open; Task-2 was static balance with eyes closed; Task-3 involved dynamic balance on an unstable surface with eyes open. A wireless functional near-infrared spectroscopy (fNIRS) system measured cortical activity, including the bilateral DLPFC, pre-motor cortex (PMC) and supplementary motor area (SMA), the primary motor cortex (M1), the primary somatosensory cortex (S1), and a force platform measured balance parameters during upright stance. Results: The two-way repeated measures ANOVA results showed significant interaction in bilateral PMC/SMA activation. Moreover, patients with CLBP had significantly increased right DLPFC activation and higher sway 32 area and velocity than healthy controls during upright stance. Discussion: Our results imply that PMC/SMA and DLPFC maintain standing balance. The patients with CLBP have higher cortical activity and upright stance control deficits, which may indicate that the patients with CLBP have low neural efficiency and need more motor resources to maintain balance.

Metabolic disposition of [14 C]-abivertinib, an epidermal growth factor receptor tyrosine kinase inhibitor: Role of glutathione conjugation.

AIMS: To determine the absorption, distribution, metabolism and excretion of abivertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Seven patients with advanced NSCLC were given a single 200 mg/83 µCi oral suspension of [14 C]-abivertinib. Blood, urine and faeces were collected. Mass balance of radioactivity, the pharmacokinetics of abivertinib, and the total radioactivity were determined. Metabolite profiling and characterisation were performed. RESULTS: The mean recovery was 82.16%, with 2.38 and 79.78% of the radioactive dose excreted in urine and faeces, respectively. The unchanged abivertinib was the major radioactive component detected in plasma within the first 24 hours after dosing, accounting for 59.17% of the total drug-related radioactivity. Abivertinib in urine accounted for only 0.96% of the administered dose, whereas in faeces it accounted for 33.36%. Eight metabolites were detected and characterised in plasma, among which MII-7, a product of cysteine glycine conjugate, was the only circulating metabolite, accounting for approximate 10.6% of the total drug-related exposure. MII-2 (an abivertinib cysteine-glycine adduct) and M7 (a reduced product of abivertinib) were the 2 major metabolites in the excreta, accounting for 20.0 and 12.4%, respectively, of the drug-related radioactivity in faeces. CONCLUSION: Following a single oral administration, the unchanged abivertinib was the predominant drug-related material in plasma, urine and faeces. The drug-related materials were primarily eliminated via the faecal route. Direct glutathione conjugation of abivertinib played a significant role in the metabolic clearance and metabolite exposure of abivertinib.

Mass balance, metabolic disposition, and pharmacokinetics of [14C]ensartinib, a novel potent anaplastic lymphoma kinase (ALK) inhibitor, in healthy subjects following oral administration.

PURPOSE: Ensartinib is a novel, potent and highly selective inhibitor of anaplastic lymphoma kinase (ALK) that has promising clinical activity and low toxicity in patients with ALK-positive non-small cell lung cancer. This study was conducted to investigate the pharmacokinetics, metabolism and excretion of ensartinib following a single 200 mg/100 µCi oral dose of radiolabeled ensartinib to healthy subjects. METHODS: Six healthy male subjects were enrolled and administrated an oral suspension in a fasted state. Blood, urine and feces were collected. Radioactivity concentrations were measured by liquid scintillation counting and plasma concentrations of ensartinib by liquid chromatography-tandem mass spectrometry. Both techniques were applied for metabolite profiling and characterization. RESULTS: The mean total recovery was 101.21% of the radiolabeled dose with 91.00% and 10.21% excreted in feces and urine, respectively. Unchanged ensartinib was the predominant drug-related component in urine and feces, representing 4.39% and 38.12% of the administered dose, respectively. Unchanged ensartinib and its metabolite M465 were the major circulating components, accounting for the same 27.45% of the plasma total radioactivity (AUC0-24h pool), while other circulating metabolites were minor, accounting for less than 10%. Mean Cmax, AUC0-∞, T1/2 and Tmax values for ensartinib in plasma were 185 ng/mL, 3827 h ng/mL, 18.3 h and 3.25 h, respectively. The total radioactivity in plasma was cleared with terminal half-life of 27.2 h. Treatment with ensartinib was well tolerated, and no serious adverse events were reported. CONCLUSION: It was well tolerated in the six healthy male subjects following a single oral administration of 200 mg/100 µCi dose of ensartinib. Besides unchanged ensartinib, metabolite of M465 was the predominant circulating drug-related component. The drug was primarily eliminated in feces. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03804541.

A phase I study to investigate the metabolism, excretion, and pharmacokinetics of [14C]fruquintinib, a novel oral selective VEGFR inhibitor, in healthy Chinese male volunteers.

PURPOSE: Fruquintinib (HMPL-013) is a novel, potent, and highly selective tyrosine kinase inhibitor targeting the vascular endothelial growth factor receptors (1, 2 and 3). This study was conducted to investigate the metabolism, excretion, and pharmacokinetics of HMPL-013 after a single oral dose to healthy Chinese men. METHODS: Six subjects were administrated an oral suspension containing 5 mg of 14C-labeled HMPL-013 (100 µCi) in a fasted state. Blood and excreta samples were collected at the designated time points or intervals for pharmacokinetics and radiometric analyses. Safety assessments were conducted throughout the study. RESULTS: Over a 336-h post-dose collection period, mean recovery was 90.11% of the radiolabeled dose, with 60.31% in urine and 29.80% in feces. Mean C max, AUC0-∞, and T max for HMPL-013 in plasma were 113 ng/mL, 4797 h ng/mL, and 2 h, respectively. Radioactivity and HMPL-013 were cleared from circulation with terminal half-lives of 41.1 and 33.4 h. HMPL-013 was the predominant circulating radioactive component, representing 72.48% of the total radioactivity. M11 was the major circulating metabolite, accounting for 17.31% of the total radioactivity. An additional seven circulating metabolites were identified, each accounting for less than 5% of the total radioactivity. In urine, HMPL-013 accounted for only 0.50% of the administered dose. Three major metabolites M285, M381, and M409-4 were identified in urine accounting for 10.48, 21.16, and 8.92% of the dose, respectively. In feces, HMPL-013 accounted for 5.34% of the dose. M205, M365-2, and M380 were the major metabolites, accounting for 2.29, 3.30, and 2.59% of the dose, respectively. CONCLUSION: HMPL-013 was well tolerated and absorbed rapidly, with parent compound being the predominant circulating component. HMPL-013 was extensively metabolized prior to excretion, and urine was the major route of excretion.

Risk of metastasis among rib abnormalities on bone scans in breast cancer patients.

Bone scan abnormalities, especially rib lesions, are often confusing for physicians due to a high number of false-positive lesions. This study investigated risk factors that are associated with bone metastasis in 613 breast cancer patients with bone scan abnormalities. Significantly increased rates of bone metastasis were observed in patients with multiple lesions, large tumor sizes, and lymph node involvement. In addition, patients with concurrent lesions of rib and other sites exhibited a significant higher rate of metastatic disease compared to those with other site lesions (P = 0.009). In the subset of 324 patients with rib abnormalities, the rate of metastasis was extremely low in patients with pure rib lesions (1.2%; 95% CI: 0.1%-4.1%). Concurrent lesions of rib and other sites were more likely to be rib metastasis compared to pure rib lesions (P < 0.001). Moreover, multiple rib lesions and lesions located on bilateral ribs were more likely to be rib metastasis (P < 0.001). Our data suggest that patients with pure rib abnormalities could be recommended for follow-up only. However, if concurrent lesions of rib and other sites were detected on bone scans, additional radiological examinations should be performed to patients.

Diagnostic value of cystatin C and glomerular filtration rate formulae in Chinese nonelderly and elderly populations.

BACKGROUND: Serum cystatin C has been recognized as a surrogate marker for serum creatinine (SCr). However, whether cystatin C and cystatin C-based glomerular filtration rate (GFR) formulae offer any diagnostic value in nonelderly and elderly subjects has rarely been investigated. METHODS: Reference GFR (rGFR) values were established using the 99mTc-DTPA renal dynamic imaging method. Nine GFR formulae were used to predict estimated GFR (eGFR). RESULTS: A total of 534 Chinese participants were enrolled. Cystatin C had a better diagnostic value than SCr. The superiority of cystatin C was more distinctly observed in the elderly. Combined cystatin C and SCr gave similar diagnostic values to cystatin C alone (p>0.05). Compared with single markers, GFR prediction formulae improved accuracy. Each formula had its own characteristics and applicability. Most formulae predicted with higher accuracy in the elderly than they did in the nonelderly. In chronic kidney disease (CKD) stage 1, the CKD-EPI formula had the least bias and the highest accuracy for the nonelderly, while the Hojs and Ma formulae performed best for the elderly. In the CKD stage 2-3, the Macisaac formula gave the most accurate eGFR. In the CKD stage 4-5, it was the CG formula that gave the closest estimate to the rGFR. CONCLUSIONS: Cystatin C could be superior to SCr, particularly in the elderly; however, cystatin C formulae and SCr formulae may possess their own applicability in different CKD stages and age groups. At present, it is not possible to say that cystatin C formulae are superior to SCr formulae.

18F-FDG PET/CT and PET for evaluation of pathological response to neoadjuvant chemotherapy in breast cancer: a meta-analysis.

BACKGROUND: Neoadjuvant chemotherapy is increasingly the treatment for patients with inoperable breast cancer. Considering the side-effects of chemotherapy, there is a need for early evaluating response to neoadjuvant chemotherapy. PURPOSE: To determinate the diagnostic performance of 18F-fluorodeoxyglucose position emission tomography/computed tomography (FDG PET/CT) and FDG PET for evaluating response to neoadjuvant chemotherapy in patients with breast cancer. MATERIAL AND METHODS: "PubMed" (MEDLINE included) database, EMBASE, and Cochrane Database of Systematic Reviews were searched for relevant articles. We assessed the methodological quality of included study with Quality Assessment of Diagnosis Accuracy Studies (QUADAS) score tool, and used "Meta-DiSc" statistic software to obtain pooled estimates of sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver-operating characteristic (SROC) curve. RESULTS: Seventeen studies (a total of 781 subjects) met the inclusion criteria. The pooled sensitivity was 0.840 (95% confidence interval [CI] 0.796-0.878). The pooled specificity was 0.713 (95% CI 0.667-0.756). For FDG PET/CT (10 studies included), the pooled sensitivity was 0.847 (95% CI 0.793-0.892), the pooled specificity was 0.661 (95% CI 0.598-0.720). The pooled likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR) were 2.835 (95% CI 1.640-4.900), 0.221 (95% CI 0.160-0.305), and 17.628 (95% CI 7.431-41.818). The area under the SROC curve (AUC) was 0.8934. For FDG PET (7 studies included), the pooled sensitivity and specificity were 0.826 (95% CI 0.741-0.892) and 0.789 (95% CI 0.719-0.849). The pooled LR + , LR-, and DOR were 3.601 (95% CI 2.601-4.986), 0.242 (95% CI 0.157-0.374), and 13.641 (95% CI 7.433-25.030). The AUC was 0.8764. CONCLUSION: Our results indicate that FDG PET/CT and PET have reasonable sensitivity in evaluating response to neoadjuvant chemotherapy in breast cancer; however, the specificity is relative low. The combination of other imaging methods with FDG PET/CT or PET is recommended.

¹8F-FDG-PET and ¹8F-FDG-PET/CT in the detection of recurrent or metastatic medullary thyroid carcinoma: a systematic review and meta-analysis.

The aim of this study was to investigate diagnostic performance of (18) F-fluorodeoxyglucose position emission tomography (FDG-PET) and PET/computed tomography (PET/CT) for detection of recurrent or metastatic medullary thyroid carcinoma (MTC) in patients after surgery with a meta-analysis. MEDLINE and EMBASE databases were searched for relevant articles. Two investigators independently extracted the data about study characteristics and examination results. Pooled estimates of sensitivity of FDG-PET or FDG-PET/CT were obtained. Fifteen studies met all inclusion criteria. The sensitivity of FDG-PET ranged from 0.47 (95% confidence intervals (CI): 0.21-0.73) to 0.96 (95%CI: 0.86-0.99), the sensitivity of FDG-PET/CT ranger from 0.47 (95% CI: 0.31-0.64) to 0.80 (95% CI: 0.65-0.90). The pooled sensitivities of FDG-PET and PET/CT were 0.68 (95% CI: 0.64-0.72) and 0.69 (95% CI: 0.64-0.74), respectively. There was no statistic significant between FDG-PET and PET/CT. Our results indicate that FDG-PET or FDG-PET/CT has reasonable sensitivity in detecting recurrent or metastatic MTC after primary surgery. However, no single diagnostic technique is able to reliably demonstrate the full extent of disease in patients with recurrent or metastatic MTC, the combination of cross-sectional radiography with FDG-PET or PET/CT is recommended.

Comparison of 18F-FDG PET/CT with bone scintigraphy for detection of bone metastasis: a meta-analysis.

BACKGROUND: The skeleton is one of the favorable sites for the metastasis of almost all human malignant neoplasms. An accurate diagnosis of bone metastasis is crucial for the patient's staging and management. PURPOSE: To investigate and compare diagnostic performance of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and bone scintigraphy (BS) for detection of bone metastasis in malignancies using meta-analysis. MATERIAL AND METHODS: PubMed (Medline included) was searched for relevant articles. We assessed the methodological quality with Quality Assessment of Diagnosis Accuracy Studies (QUADAS) score tool, and used statistical software to obtain pooled estimates of sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver-operating characteristic (SROC) curve. RESULTS: Six studies met inclusion criteria. For 18F-FDG PET/CT, the pooled sensitivity and specificity were 0.934 and 0.975, respectively. The pooled positive likelihood ratio (LR+), negative likelihood ratio (LR-) and diagnostic odds ratio (DOR) were 34.990, 0.068 and 559.02, respectively. The area under the SROC curve was 0.9854. For BS, the pooled sensitivity, specificity, LR + , LR- and DOR were 0.706 (0.642-0.764), 0.911 (0.896-0.926), 13.982 (2.419-80.817), 0.319 (0.143-0.712), and 60.420 (21.393-170.64), respectively. The area under the SROC curve was 0.9386. CONCLUSION: The results indicate that 18F-FDG PET/CT do have both higher sensitivity and specificity than bone scintigraphy for detecting metastatic bone tumor. However, further research is needed to evaluate the diagnostic performance of 18F-FDG PET/CT and BS in each common malignancy.

A meta-analysis of 99mTc-MIBI SPECT for detection of recurrent glioma after radiation therapy.

We performed a meta-analysis of the diagnostic accuracy of technetium-99m methoxyisobutylisonitrile ((99m)Tc-MIBI) single photon emission computed tomography (SPECT) for assessment of glioma recurrence in patients after radiation therapy. The "PubMed" database was searched for relevant papers. Two reviewers extracted the data on study characteristics and examination results independently, and assessed the methodological quality of each included study. Pooled estimates of sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve were obtained. Six investigations met inclusion criteria. The sensitivity ranged from 0.733 to 0.984, and the specificity ranged from 0.750 to 0.955. The pooled sensitivity and specificity were 0.898 and 0.919. The positive likelihood ratio (LR+) ranged from 3.800 to 19.381, the negative likelihood ratio (LR-) ranged from 0.017 to 0.311, and the DOR ranged from 16.500 to 567.00. The pooled LR+, LR- and DOR were 10.913, 0.115 and 94.062, respectively. The area under the SROC curve was 0.9650. Our results indicate that (99m)Tc-MIBI SPECT is a highly sensitive and specific modality in assessing patients with suspected glioma recurrence after radiation therapy.

A novel approach to transplanting bone marrow stem cells to repair human myocardial infarction: delivery via a noninfarct-relative artery.

Bone marrow stem cells are able to repair infarcted human myocardium following intracoronary transplantation via the infarct-relative artery. However, traditional reperfusion strategies fail to open the artery in some patients, making effective delivery impossible. Our previous study demonstrated a safe and efficient approach to delivering bone marrow stem cells via a noninfarcted artery in an animal myocardial infarction model. The objective of the present study was to evaluate the safety and feasibility of autologous bone marrow mesenchymal stem cell transplantation via such an approach in patients with acute myocardial infarction (AMI). Sixteen patients with anterior AMI who had successfully undergone percutaneous coronary intervention (PCI) were enrolled in this pilot, randomized study. Three weeks after PCI, cultured bone marrow mesenchymal stem cells were injected into the myocardium via either the infarct-relative artery (left anterior descending branch artery, LAD) or a noninfarct-relative artery (right coronary artery, RCA). The safety and feasibility of the cell infusion were evaluated during the procedure and during 6 months of follow-up. In addition, 2D echocardiography, technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) and 18F-deoxyglucose single photon emission computed tomography were employed to examine cardiac function, myocardial perfusion, and viable cardiomyocytes, respectively, at day 4 after PCI and 6 months after the cell infusion. There were no arrhythmia and any other side-effects, including infections, allergic reactions or adverse clinical events, during, immediately after, or 6 months after cell transplantation. Cardiac function and myocardial perfusion had improved 6 months after PCI/bone marrow stem cells transplantation. Viable cardiomyocytes metabolism was detected in the infarcted areas in both groups after the cell infusion, as demonstrated by 18F-deoxyglucose. Intracoronary infusion of autologous bone marrow mesenchymal stem cells via a noninfarct-relative artery appears safe and feasible in the treatment of patients with AMI.

Neovascularization and cardiomyocytes regeneration in acute myocardial infarction after bone marrow stromal cell transplantation: comparison of infarct-relative and noninfarct-relative arterial approaches in swine.

BACKGROUND: Adult bone marrow stromal cells could differentiate into myogenic endothelial progenitor cells and has been investigated for the potential value in regeneration. Recently, it has been reported that bone marrow cells (BMCs) are able to repair the infracted myocardium by intracoronary transplantation via infarct-related artery in humans. Unfortunately, we cannot open the infarcted artery by traditional reperfusion therapies in some patients. We investigate the hypothesis that BMCs transplantation might get the same effect via noninfarct-relative artery. This alternative approach may have potential application in clinical practice. METHODS: A swine myocardial infarction model was established by distal left anterior descending artery ligation. Bone marrow stromal cells isolated, culture-expanded and labeled with bromodeoxyuridine (BrdU) were used as donor cells. Four weeks after coronary artery ligation, either a graft of 5x10(6) donor cells (n=12) or culture medium (n=6) was infused into infarcted area via infarct-relative artery (left coronary artery, n=6) and noninfarct-relative artery (right coronary artery, n=6). Heart function was evaluated by gate cardiac perfusion imaging before the transplantation and 4 weeks after transplantation. The donor cell localization and differentiation were identified by immunohistochemical staining for BrdU and beta-myosin heavy chain (beta-MHC) and angiogenesis was assessed by immunohistochemical staining for alpha-smooth muscle actin (alpha-SMA) and Factor VIII. RESULTS: Gate cardiac perfusion imaging demonstrated that the cardiac function was significantly improved after the stromal cell transplantation via both infarct-relative and noninfarct-relative coronary arteries compared with control group (45.03+/-2.71 and 47.78+/-2.64 vs 30.36+/-2.76, P<0.05). Four weeks after transplantation, BrdU and beta-MHC positive cells were detected within the infarct area. Vessel densities in infarct area and infarct border area were increased significantly in both transplantation groups compared to the control group (98.68+/-5.32 and 87.49+/-6.04 vs 48.46+/-4.88, P<0.05). CONCLUSIONS: Transplantation of bone marrow stromal cell via both infarct-relative and noninfarct-relative coronary arteries improved heart function in the myocardial infarction animals by stimulating cardiomyocyte regeneration and angiogenesis.

[Hepatocyte growth factor did not enhance the effects of bone marrow-derived mesenchymal stem cells transplantation on cardiac repair in a porcine acute myocardial infarction model].

OBJECTIVE: To evaluate the impact of combined therapy with transplanting bone marrow-derived mesenchymal stem cells (BM-MSCs) via noninfarct-relative artery and hepatocyte growth factor (HGF) in a porcine myocardial infarction (MI) model. METHODS: BM-MSCs were obtained from pig bone marrow, expanded in vitro with a purity of > 50%. MI was induced by ligating the distal left anterior descending artery in pigs. Eighteen animals received BM-MSCs cells (5 x 10(6)/ml, n = 6), BM-MSCs cells (5 x 10(6)/ml) plus HGF (4 x 10(9) pfu, n = 6) or equal volume culture medium (IMDM) via non-infarct-related artery at four weeks after MI. Gated myocardial perfusion imaging and coronary angiography were performed before and four weeks after transplantations. Histological examination was also performed 4 weeks after transplantation. RESULTS: LVEF measured by gated myocardial perfusion imaging was similar among groups before transplantation and significantly increased in BM-MSCs (45 +/- 3 vs. 34 +/- 2%, P < 0.05) or BM-MSCs + HGF (46 +/- 6 vs. 34 +/- 3%, P < 0.05) treated animals while remained unchanged in IMDM (30 +/- 3 vs. 32 +/- 2%) treated animals 4 weeks post transplantation. Similarly, capillary density was also significantly higher and myocardial perfusion defect scores significantly decreased in BM-MSCs or BM-MSCs + HGF treated hearts than that in IMDM treated hearts. However, all these changes were similar between BM-MSCs and BM-MSCs + HGF groups. Rentrop score was similar before and 4 weeks after transplantation among various groups. CONCLUSION: HGF in combination with BM-MSCs transplantation did not enhance the cardiac repair effects of BM-MSCs transplantation alone and BM-MSCs transplantation did not improve collateral circulation in this model.

131I-chTNT radioimmunotherapy of 43 patients with advanced lung cancer.

UNLABELLED: The treatment of advanced lung cancer remains a major challenge in clinical medicine, justifying an urgent need for new therapeutic approaches. In a rather unique international collaboration, 43 patients with advanced lung cancer were treated using iodine-131-labeled tumor necrosis therapy chimeric antibody (131I-chTNT). METHODS: Patients were treated either with intravenous (i.v.) infusion (n = 22), intratumoral injection using a computer tomography (CT)-guided catheter (n = 16), or combination i.v. and intratumoral infusion (n = 5). All patients, regardless of route of administration, received 2 doses of 131I-chTNT on days 1 and 14. RESULTS: The results showed that of those patients receiving i.v. injection alone, 2 achieved partial response (PR) (9%), 16 had stable disease (73%), and 4 progressed (18%). Of those patients receiving intratumoral injection only, 1 had a complete response (CR) (6%), 8 achieved PR (50%), 7 had stable disease (44%), and none (0%) progressed. Finally, of those patients receiving both i.v. and intratumoral administration, 1 had a CR (20%), 1 achieved PR (20%), 2 had stable disease (40%), and 1 (20%) showed progression. CONCLUSIONS: These promising results demonstrate that sufficient doses of radiolabeled antibody can be safely delivered to tumors to cause significant therapeutic effects in advanced lung cancer.

Clinical cellular cardiomyoplasty: technical considerations.

Three patients, all with a history of coronary heart disease, underwent coronary artery bypass grafting and implantation of autologous satellite cells. Satellite cells were isolated from muscle biopsies of the right vastus lateralis muscle after enzymatic treatment. While the heart was still under hypothermic cardioplegia, 4 mL of cell suspension divided into approximately 40 doses was injected into the ventricular wall of the ischemic area. Less than 5 minutes were required to complete the cell implantation. All patients survived the procedure, without obvious arrhythmia, had an uneventful recovery, and were discharged from the hospital. At 3 to 4 months follow-up examination, increased left ventricular ejection fraction, decreased left ventricular diastolic diameter, as well as improved ventricular wall thickness and perfusion at the satellite cell implantation sites were observed. Our experience indicated the safety and early benefit of cellular cardiomyoplasty using autologous satellite cells.

[The clinical study of I-131 labeled chimeric TNT antibody targeting therapy to 43 patients with advanced lung cancer].

BACKGROUND: To analysis and evaluate the efficacy of I-131 labeled chimeric TNT antibody ( ¹³¹I-chTNT MAb) targeting therapy in advanced lung cancer, and then choose the best way of administration. METHODS: Forty-three patients with advanced lung cancer were treated by 3 different protocols using ¹³¹I-chTNT MAb. Their diagnosis was confirmed by histology and there were 30 cases in stage IIIB and 13 cases in stage IV, 32 cases were newly diagnosed and 11 cases were retreated. All patients were divided into three groups and treated with different methods: (1)iv infusion (n=22); (2) intratumoral injection (n=16); and (3) combination iv (25% of total dosage) and intratumoral (75%) infusion (n=5). All patients received radiolabeled MAb at a total dosage of 2.96×107 Bq/kg on days 1 and 14. RESULTS: There were 2 complete response (4.7%), and 11 partial response (25.6%), the total response rate was 30.2% (13/43) in all patients. For those patients receiving iv injection alone, the response rate was 9.1%. For those patients receiving intratumoral injection alone, the response rate was 56.3%. There was significant difference between them (P < 0.01 ). The main toxicity was reversible bone marrow suppression, 2 cases (4.7%) with grade III leukopenia and 3 cases (7.0%) grade III thrombocytopenia. CONCLUSIONS: ¹³¹I-chTNT has significant therapeutic effects on advanced lung cancer and the intratumoral injection is the best way of administration.