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1.
Medicine (Baltimore) ; 103(21): e38136, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38787978

ABSTRACT

INTRODUCTION: Inflammatory myofibroblastic tumor (IMT) is a rare invasive soft tissue tumor. Many IMTs are positive for anaplastic lymphoma kinase (ALK) with ALK gene fusion; other gene mutations have also been reported, which indicates a key role for genetic testing and the development of target therapy to optimize treatment strategies. PATIENT CONCERNS: We report 2 patients who obtained clinical benefits following targeted treatment with ensartinib. DIAGNOSIS: The first patient was diagnosed as IMT, with TFG-ROS1 fusion gene mutation. The second patient was IMT harboring the ALK-STRN fusion gene mutation. INTERVENTIONS: We performed gene testing for these 2 patients. According to the test result, both patients received ensartinib 225 mg QD as targeted therapy for a 30-day cycle. OUTCOMES: The first patient achieved partial remission and maintained a stable state for 14.7 months. The second patient was treated for 10 months and reached complete remission after 5 months and is currently still benefiting from treatment. Treatment-related side effects were mild in both patients. CONCLUSION: Our cases provided some new insights and approaches for the clinical diagnosis and treatment of IMT.


Subject(s)
Neoplasms, Muscle Tissue , Humans , Female , Male , Neoplasms, Muscle Tissue/drug therapy , Neoplasms, Muscle Tissue/genetics , Neoplasms, Muscle Tissue/pathology , Adult , Anaplastic Lymphoma Kinase/genetics , Middle Aged , Soft Tissue Neoplasms/drug therapy , Soft Tissue Neoplasms/genetics , Soft Tissue Neoplasms/pathology , Antineoplastic Agents/therapeutic use
2.
J Hematol Oncol ; 16(1): 50, 2023 05 08.
Article in English | MEDLINE | ID: mdl-37158938

ABSTRACT

BACKGROUND: QL1706 (PSB205) is a single bifunctional MabPair (a novel technical platform) product consisting of two engineered monoclonal antibodies (anti-PD-1 IgG4 and anti-CTLA-4 IgG1), with a shorter elimination half-life (t1/2) for CTLA-4. We report results from a phase I/Ib study of QL1706 in patients with advanced solid tumors who failed standard therapies. METHODS: In the phase I study, QL1706 was administered intravenously once every 3 weeks at one of five doses ranging from 0.3 to 10 mg/kg, and the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of QL1706 were investigated. In the phase Ib study, QL1706 was administered at the RP2D intravenously every 3 weeks, and the preliminary efficacies in non-small cell lung cancer (NSCLC), nasopharyngeal carcinoma (NPC), cervical cancer (CC), and other solid tumors were evaluated. RESULTS: Between March 2020 and July 2021, 518 patients with advanced solid tumors were enrolled (phase I, n = 99; phase Ib, n = 419). For all patients, the three most common treatment-related adverse events (TRAEs) were rash (19.7%), hypothyroidism (13.5%), and pruritus (13.3%). The TRAEs and immune-related adverse events (irAEs) of grade ≥ 3 occurred in 16.0% and 8.1% of patients, respectively. In phase I, 2 of 6 patients in the 10mg/kg group experienced dose-limiting toxicities (DLTs) (grade 3 thrombocytopenia and grade 4 immune-mediated nephritis), so the maximum tolerated dose (MTD) was reached at 10 mg/kg. The RP2D was determined to be 5 mg/kg based on comprehensive analysis of tolerability, PK/PD, and efficacy. For all patients who received QL1706 at the RP2D, the objective response rate (ORR) and median duration of response were 16.9% (79/468) and 11.7 months (8.3-not reached [NR]), respectively; and the ORRs were 14.0% (17/121) in NSCLC, 24.5% (27/110) in NPC, 27.3% (15/55) in CC, 7.4% (2/27) in colorectal cancer, 23.1% (6/26) in small cell lung cancer. For immunotherapy-naive patients, QL1706 exhibited promising antitumor activities, especially in NSCLC, NPC, and CC, with ORRs of 24.2%, 38.7%, and 28.3%, respectively. CONCLUSIONS: QL1706 was well tolerated and demonstrated promising antitumor activity in solid tumors, especially in NSCLC, NPC, and CC patients. It is currently being evaluated in randomized phase II (NCT05576272, NCT05179317) and phase III (NCT05446883, NCT05487391) trials. Trial Registration ClinicalTrials.gov Identifier: NCT04296994 and NCT05171790.


Subject(s)
Antibodies, Bispecific , Antineoplastic Agents , CTLA-4 Antigen , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Nasopharyngeal Carcinoma , Uterine Cervical Neoplasms , Female , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , CTLA-4 Antigen/antagonists & inhibitors , Immunoglobulin G , Lung Neoplasms/drug therapy , Uterine Cervical Neoplasms/drug therapy , Nasopharyngeal Carcinoma/drug therapy
3.
Laryngoscope Investig Otolaryngol ; 8(2): 435-440, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37090874

ABSTRACT

Recurrent respiratory papillomatosis (RRP) is a human papilloma virus (HPV)-driven benign neoplasm, affecting larynx, trachea, and even lung, leading to voice disorders, airway obstruction, and postobstructive pneumonia. Several case reports have documented the promising efficacy of intravenous bevacizumab in reducing the need for surgical intervention among RRP patients. Herein, we present our experience on systemic bevacizumab for pediatric patients with aggressive RRP. Methods: We retrospectively analyzed clinical, laboratory, radiological, and bronchoscopy findings of pediatric patients with aggressive RRP treated with systemic bevacizumab from July 26, 2021 to March 1, 2022. Results: Eight consecutive patients were included. Median age at treatment initiation was 5.5 (range 2.5-8) years old. Twenty-five percentage (2/8) of patients experienced tracheotomy. Pulmonary papilloma was present in 62.5% (5/8) patients. Patients received median 10 cycles of bevacizumab (range 5-12). Patients received initial dosing of 4-7.5 mg/kg every 2-10 weeks of bevacizumab and subsequently extended after achieving the maximum response. None of the patients required surgical intervention during a median 10 (range 8.2-15.4) months follow-up after initiating bevacizumab treatment. Both patients with evaluable lung lesions showed objective response. Only Grade 1 abdominal pain and Grade 1 hyperuricemia were recorded. Conclusion: Systemic bevacizumab seems to be a well-tolerated and effective treatment option for pediatric patients with aggressive RRP.

4.
Oncologist ; 28(5): 449-452, 2023 05 08.
Article in English | MEDLINE | ID: mdl-36913260

ABSTRACT

Glioblastoma (GBM) is the most common primary brain tumor, and patients with GBM have a universally poor prognosis. Genomic profiling has detected epidermal growth factor receptor (EGFR) gene alterations in more than half of GBMs. Major genetic events include amplification and mutation of EGFR. Interestingly, we identified an EGFR p.L858R mutation in a patient with recurrent GBM for the first time. Based on the genetic testing results, almonertinib combined with anlotinib and temozolomide was administered and obtained 12 months of progression-free survival after the diagnosis of recurrence as the fourth-line treatment. This is the first report that an EGFR p.L858R mutation was identified in a patient with recurrent GBM. Furthermore, this case report represents the first study applying the third-generation TKI inhibitor almonertinib in the treatment of recurrent GBM. The results of this study indicate that EGFR might be a new marker for the treatment of GBM with almonertinib.


Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Temozolomide/pharmacology , Temozolomide/therapeutic use , Glioblastoma/drug therapy , Glioblastoma/genetics , ErbB Receptors/genetics , Mutation , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Brain Neoplasms/metabolism
5.
Sci Rep ; 13(1): 3385, 2023 02 28.
Article in English | MEDLINE | ID: mdl-36854710

ABSTRACT

Angiogenesis inhibitors (AIs) and immune checkpoint inhibitors (ICIs) are new treatment options for advanced soft tissue sarcoma (STS) patients. This study evaluated the efficacy and safety of AIs plus ICIs in patients with advanced STS. A retrospective cohort study was performed on STS patients treated with AIs and ICIs at Shandong Cancer Hospital and Institute between August 2020 and December 2021. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and adverse events. Thirty-three patients were enrolled; 27 were evaluable for objective response. The ORR and DCR were 48.1% (95% CI 30.7-66.0%) and 85.2% (95% CI 67.5-94.1%). With a median follow-up of 7.6 months (range, 0.8-25.5), the median PFS for all 33 patients was 8.90 months (95% CI 5.98-11.82). The median OS was not reached. The most common treatment-related adverse events (TRAEs) of any grade were hypertension (50.0%), ECG T-wave abnormality (30.0%), hypothyroidism (26.7%), elevated alanine aminotransferase or aspartate aminotransferase (23.3%), elevated thyroid-stimulating hormone (23.3%), and fatigue (16.7%). The most common grade 3-4 TRAE was hypertension (27.3%). Three serious TRAEs (two myocarditis and one rapid atrial fibrillation) were recorded. This study suggests that adding AIs to ICIs is beneficial in STS.


Subject(s)
Angiogenesis Inhibitors , Immune Checkpoint Inhibitors , Sarcoma , Soft Tissue Neoplasms , Humans , Angiogenesis Inhibitors/adverse effects , Hypertension , Immune Checkpoint Inhibitors/adverse effects , Retrospective Studies , Sarcoma/drug therapy , Soft Tissue Neoplasms/drug therapy
6.
J Cancer Res Clin Oncol ; 149(4): 1443-1451, 2023 Apr.
Article in English | MEDLINE | ID: mdl-35482078

ABSTRACT

PURPOSE: Although immune checkpoint inhibitor monotherapy has been used as a second-line treatment in advanced non-small cell lung cancer (NSCLC), the improvement in progression-free survival (PFS) remains unsatisfactory. We investigated the feasibility of sintilimab plus chemotherapy as a second-line treatment in advanced NSCLC. METHODS: This was a phase II, single-arm, prospective study in advanced NSCLC patients who had failed standard platinum-based chemotherapy (ChiCTR1900027634, Registered 22 November 2019). Eligible patients received docetaxel 75 mg/m2 (day 1) plus sintilimab 200 mg (day 3) Q3W. Those did not progress after 4-6 cycles received sintilimab 200 mg Q3W as maintenance treatment. The primary endpoint was PFS. RESULTS: Forty patients were enrolled between October 2019 and October 2020. With a median follow-up of 12.2 months, the median PFS was 5.8 months, and the PFS rates at 6 and 12 months were 48% and 30%, respectively. The median overall survival (OS) was 12.6 months, with a 12-month OS rate of 62.0%. The overall response rate was 32.4%, and the disease control rate was 89.2%. The incidence of all and ≥ grade 3 treatment-related adverse events (TRAEs) were 65% (26/40) and 17.5% (7/40), respectively. No TRAEs-related permanent treatment discontinuation or death occurred. bTMB reduction at 6 weeks was associated with a longer PFS (NR vs 3.0 months, P < 0.0001). CONCLUSION: This prospective phase II study in China suggested that sintilimab plus docetaxel might improve PFS and tumor response with good tolerability for Chinese patients with previously treated advanced NSCLC. bTMB reduction at 6 weeks could serve as a potential predictive biomarker for this regimen.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Docetaxel , Prospective Studies , Lung Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/adverse effects
7.
Front Genet ; 13: 792466, 2022.
Article in English | MEDLINE | ID: mdl-35154272

ABSTRACT

Klippel-Trenaunay syndrome (KTS) was demonstrated as a mosaic activating PIK3CA mutations related overgrowth syndrome. We present the first case of primary pleural angiosarcoma in a 17-year-old woman with a history of KTS. The combined targeted DNA and RNA sequencing revealed an activating mutation in PIK3CA in the tumor tissue. Our case suggested an association and perhaps a causal link between the two different PIK3CA-related genetic diseases.

8.
Front Oncol ; 12: 1072361, 2022.
Article in English | MEDLINE | ID: mdl-36741690

ABSTRACT

Background: Metastatic pheochromocytomas and paragangliomas are rare neuroendocrine tumors with a poor prognosis. Bladder paraganglioma concomitant with urothelial papilloma is even rarer. However, the rate of tumor response to cyclophosphamide-vincristine-dacarbazine (CVD) chemotherapy and 5-year overall survival for patients with metastatic PPGLs remained lower. We described, for the first time, a case of a patient with multiple metastatic bladder PGL who received octreotide LAR combined with CVD chemotherapy after urological surgery and then octreotide therapy was continued during follow-up. Case presentation: A 43-year-old male patient was admitted to the urology department for frequent micturition syncope concomitant with malignant hypertension. Preoperative findings were elevated levels of normetanephrine in 24-h urine or plasma. CT and MRI indicated diagnosis of suspicious bladder paraganglioma. Transurethral resection of bladder tumor combined with laparoscopic partial cystectomy was performed successfully after preoperative phenoxybenzamine with aggressive volume repletion for 7 days. The result of postoperative pathology was immediate-risk functional bladder paraganglioma (T2N0M0, Stage II) concomitant with urothelial papilloma, and the immunohistochemistry results of PPGL were positive for Ki-67 (15%), SDHB, CgA, and SSTR2. The patient achieved enhanced recovery with normal urination and no syncope after surgery. However, the results of 18F-FDG and 18F-DOTATATE PET/CT found that the metastatic localizations of bladder PGLs were in the liver, lung, and bones at the 8th month after surgery. The patient received octreotide long-acting repeatable plus six courses of CVD chemotherapy for 6 months, and then octreotide therapy was continued every 3 months until now. Metastatic localizations were stable in CT scans, and vanillylmandelic acid in 24-h urine was maintained at lower levels during follow-up. Conclusion: Octreotide long-acting repeatable plus CVD chemotherapy after surgery could achieve stable disease in the case with multiple metastatic bladder PGLs, and the following octreotide therapy could maintain a state of stable disease during the period of 6-month follow-up.

9.
J Immunother Cancer ; 10(12)2022 12.
Article in English | MEDLINE | ID: mdl-36600554

ABSTRACT

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.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Circulating Tumor DNA , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Docetaxel/therapeutic use , Circulating Tumor DNA/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Disease Progression
10.
Tohoku J Exp Med ; 250(4): 263-270, 2020 04.
Article in English | MEDLINE | ID: mdl-32321873

ABSTRACT

Lung cancer is the leading cause of cancer-related death, and adenocarcinoma is the most common histological type of lung cancer. Syntaxin-binding protein 1 (STXBP1) is essential for exocytosis of secretory vesicles. Since exocytosis is the basic cellular process of cells, we investigated STXBP1 expression and clinical significance in lung adenocarcinoma. We performed quantitative real-time polymerase chain reaction in 20 pairs of lung adenocarcinoma and paired normal tissues, and demonstrated that the relative expression levels of STXBP1 mRNA in lung adenocarcinoma was significantly higher than those in normal lung tissues. We then carried out immunohistochemistry (IHC) to determine the expression profile of STXBP1 in 276 lung adenocarcinoma specimens, and categorized patients into subgroups with low or high STXBP1 expression, based on the IHC score. Moreover, STXBP1 expression phenotypes were categorized as membrane, cytoplasm, and mixed expression (both membrane and cytoplasm) expression. High STXBP1 protein accounted for 58.0% of all the 276 cases (160/276), and membrane, cytoplasm or mixed STXBP1 accounted for 28.75%, 25.63% and 45.63% in the 160 cases of high STXBP1 expression. The clinical significances of these phenotypes were evaluated by analyzing their correlation with clinicopathological factors, as well as their prognostic values. Consequently, the whole STXBP1 expression or membranal STXBP1 expression were correlated with poor prognosis and were independent prognostic factors of lung adenocarcinoma. The whole and membranal STXBP1 expression are independent prognostic factors of lung adenocarcinoma. STXBP1 detection is capable to help screen patients who may have poor prognosis and strengthen the adjuvant therapy more precisely.


Subject(s)
Adenocarcinoma of Lung/metabolism , Adenocarcinoma of Lung/pathology , Cell Membrane/metabolism , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Munc18 Proteins/metabolism , Cohort Studies , Female , Humans , Intracellular Space/metabolism , Male , Middle Aged , Prognosis
11.
Onco Targets Ther ; 9: 315-20, 2016.
Article in English | MEDLINE | ID: mdl-26834490

ABSTRACT

BACKGROUND: MDS1 and EVI1 complex locus protein EVI1 (MECOM) is an oncogenic transcription factor in several kinds of cancers. However, the clinical significance of MECOM in glioblastoma multiforme (GBM) has not been well elucidated. PATIENTS AND METHODS: Our study enrolled 86 resected samples of GBM in three medical centers. We detected the expression of MECOM in all the 86 samples by immunohistochemistry and compared the difference of MECOM mRNA between tumor tissues and adjacent tissues with real-time polymerase chain reaction. With immunoblotting, we detected the MECOM expression in different GBM cell lines. Moreover, we analyzed the correlation between MECOM expression and clinicopathologic factors with chi-square test, and evaluated the prognostic value of MECOM with univariate and multivariate analysis. RESULTS: In GBM tissue, the percentage of MECOM high expression is 41.9% (36/86). The mRNA of MECOM in tumor tissues is remarkably higher than that in adjacent tissues, indicating the oncogenic role of MECOM in GBM. MECOM exists in all the detected cell lines with different abundance. Moreover, MECOM is correlated with poorer overall survival rate (P=0.033) and can be identified as an independent prognostic factor in GBM (P=0.042). CONCLUSION: MECOM could be considered as an independent prognostic factor in GBM, predicting it as a potential and promising molecular drug target.

12.
Tohoku J Exp Med ; 238(2): 85-91, 2016 02.
Article in English | MEDLINE | ID: mdl-26753562

ABSTRACT

Vascular endothelial growth factor-C (VEGF-C) is a secreted growth factor involved in many oncogenic processes, and neuropilin-2 (NRP2) is essential for neuronal guidance as a well-acknowledged co-receptor of VEGF receptors. The overexpression of NRP2 has been reported in many types of cancers, but the significance of NRP2 in glioblastoma is not elucidated. To investigate the clinical significance of VEGF-C and NRP2 in glioblastoma, we detected their expression in 86 cases of glioblastoma with immunohistochemistry and categorized our cohort into high- and low-expression groups according to the immunohistochemistry score, which was the product of the score of staining intensity multiplied by the score reflecting the percentage of positive cells. The proportion of glioblastoma with high VEGF-C expression was 34.9% (30/86), and that with high NRP2 expression was 37.2% (32/86). The proportion of glioblastoma with high expression of both VEGF-C and NRP2 was 15.1% (13/86). Moreover, the proportion of cases with high VEGF-C and low NRP2 was 19.7% (17/86), while the proportion of cases with low VEGF-C and high NRP2 was 22.1% (19/86). The high expression of both VEGF-C and NRP2 was associated with poorer survival rate (P = 0.023), and can be identified as an independent prognostic factor in glioblastoma (P = 0.030). Moreover, cases with low NRP2 expression are easier for complete tumor resection (P = 0.038). In conclusion, the concurrent high expression of VEGF-C and NRP2 is predictive of the unfavorable prognosis in glioblastoma, indicating that the VEGF-C-NRP2 signaling pathway is a potential and promising drug target in glioblastoma therapy.


Subject(s)
Brain Neoplasms/metabolism , Glioblastoma/metabolism , Neuropilin-2/metabolism , Vascular Endothelial Growth Factor C/metabolism , Brain Neoplasms/pathology , Cell Line, Tumor , Female , Glioblastoma/pathology , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Prognosis , Proportional Hazards Models
13.
Technol Cancer Res Treat ; 15(3): 509-16, 2016 06.
Article in English | MEDLINE | ID: mdl-25948322

ABSTRACT

Circulating tumor cells are low-frequency cells that are shed into the peripheral bloodstream from a primary solid tumor and/or metastasis. Although these cells were recognized initially in 1869, it is only in the past 2 decades that they have been isolated for use as a surrogate biomarker to monitor response to therapy, evaluate prognosis, detect tumor mutations, assist in selecting personalized medicine, and enable earlier cancer diagnosis.


Subject(s)
Biomarkers, Tumor/blood , Neoplasms/pathology , Neoplastic Cells, Circulating/pathology , Humans
14.
Invest Ophthalmol Vis Sci ; 56(4): 2631-8, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25788648

ABSTRACT

PURPOSE: To investigate the longitudinal changes in choroidal thickness of the eyes of diabetic retinopathy patients during 12 weeks after panretinal photocoagulation (PRP). METHODS: This prospective, comparative study included 46 eyes undergoing four-session PRP. At baseline and 1, 4, 8, and 12 weeks after completion of the PRP treatments, subfoveal choroidal thickness (SFCT) was measured by using enhanced depth imaging optical coherence tomography. Also measured were central macular thickness (CMT) and best-corrected visual acuity (BCVA). RESULTS: The mean SFCT at baseline was 309 ± 77 µm, changing to 323 ± 78 µm, 315 ± 75 µm, 299 ± 68 µm, and 289 ± 71 µm at 1, 4, 8, and 12 weeks, respectively. This constituted a statistically significant increase at 1 week and a significant decrease at 12 weeks. The mean baseline CMT was 294 ± 92 µm, which increased significantly 1 week after PRP to 344 ± 123 µm, remaining higher at 4 weeks (340 ± 117 µm) and 8 weeks (318 ± 100 µm), but subsiding to baseline at 12 weeks (311 ± 96 µm). The mean BCVA at baseline and the last visit were 0.63 ± 0.28 logMAR and 0.53 ± 0.42 logMAR, respectively. There was no significant difference in BCVA between eyes with and without central-involved diabetic macular edema at all time points. Compared with the baseline, the mean BCVA dropped at 1 week and 4 weeks but recovered by 12 weeks. CONCLUSIONS: Choroidal thickness decreased 12 weeks after PRP, suggesting that PRP may reduce choroidal vascular permeability or cause atrophy of choroidal vessels over a 12-week period.


Subject(s)
Choroid/pathology , Diabetic Retinopathy/surgery , Laser Coagulation , Visual Acuity , Adult , Aged , Diabetic Retinopathy/pathology , Diabetic Retinopathy/physiopathology , Female , Fluorescein Angiography , Follow-Up Studies , Fundus Oculi , Humans , Male , Middle Aged , Prospective Studies , Retina/pathology , Retina/surgery , Time Factors , Tomography, Optical Coherence , Treatment Outcome
15.
Tumour Biol ; 36(3): 1595-601, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25596081

ABSTRACT

The development of colorectal cancer (CRC) spans about 5-10 years, making early detection and prevention beneficial to the survival of CRC patients. To address inconsistencies in evidence regarding O(6)-methylguanine-DNA-methyltransferase (MGMT) methylation as a potential prognostic factor in CRC, we conducted a meta-analysis to evaluate MGMT methylation in CRC patients. Fourteen studies were included in the meta-analysis after screening 120 articles. The following items were collected from each study: author, published year, country, patient gender, MGMT methylation status, and patients' disease progression. Pooled hazard ratios and odd ratios with 95% confidence intervals (CIs) were calculated using fixed or random effect models depending on the heterogeneity between studies. The overall survival of CRC patients was found not to be significantly associated with MGMT methylation. Further subgroup analysis showed that the frequency of MGMT methylation was significantly higher in CRC than in normal tissues (p < 0.00001). MGMT promoter in CRC patients was more frequently methylated than in adenoma patients. In addition, MGMT methylation was significantly increased in adenoma than in normal tissues (p < 0.0001). In conclusion, MGMT methylation is central to the development of cancer that involves a stepwise carcinogenesis of normal adenoma carcinoma cascade. However, MGMT methylation is not associated with the prognosis of CRC.


Subject(s)
Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , DNA Methylation , DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Tumor Suppressor Proteins/genetics , Adenoma/diagnosis , Adenoma/genetics , Biomarkers, Tumor/genetics , Carcinoma/diagnosis , Carcinoma/genetics , Humans , Prognosis , Promoter Regions, Genetic
16.
World J Gastroenterol ; 20(48): 18306-15, 2014 Dec 28.
Article in English | MEDLINE | ID: mdl-25561797

ABSTRACT

AIM: To explore the correlation between Twist-related protein (Twist)1, fibroblast growth factor receptor (FGFR)2 and gastric adenocarcinoma differentiation and progression. METHODS: We evaluated Twist1 and FGFR2 in 52 gastric adenocarcinoma samples by immunohistochemistry and quantitative real time polymerase chain reaction, and analyzed the correlation between Twist1, FGFR2 and cancer differentiation. We also detected Twist1 and FGFR2 expression in gastric adenocarcinoma cell lines, and evaluated Twist1 influence on FGFR2 expression. In addition, we studied the role of FGFR2 in Twist1-promoted cancer progression, including proliferation, invasion and epithelial-mesenchymal transition (EMT). RESULTS: Twist1 and FGFR2 were detected in almost all the gastric adenocarcinoma samples. Twist1 (P = 0.0213) and FGFR2 (P = 0.0310) mRNA levels had a significant association with gastric adenocarcinoma differentiation. Moreover, Twist1 and FGFR2 expression in poorly differentiated cells (SNU-1 and SNU-16) was notably higher than in well-differentiated cells (MKN-7 and MKN-28). In poorly differentiated gastric adenocarcinomas, FGFR2 mRNA level was significantly positively correlated with Twist1 mRNA level (P = 0.004). Twist1 was proved to promote FGFR2 by regulating Twist1 expression by knockdown and overexpression. Additionally, Twist1 could induce proliferation, invasion and EMT in gastric cancer; of these, FGFR2 was required for invasion and EMT, rather than proliferation. CONCLUSION: Twist1 and FGFR2 are highly associated with differentiation of gastric adenocarcinoma; Twist1 can facilitate invasion and EMT in gastric adenocarcinoma via promotion of FGFR2 expression.


Subject(s)
Adenocarcinoma/metabolism , Biomarkers, Tumor/metabolism , Cell Differentiation , Nuclear Proteins/metabolism , Receptor, Fibroblast Growth Factor, Type 2/metabolism , Stomach Neoplasms/metabolism , Twist-Related Protein 1/metabolism , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Biomarkers, Tumor/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , Disease Progression , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Neoplasm Invasiveness , Nuclear Proteins/genetics , Prognosis , RNA Interference , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Receptor, Fibroblast Growth Factor, Type 2/genetics , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Transfection , Twist-Related Protein 1/genetics , Up-Regulation
17.
Cancer Epidemiol ; 35(5): 497-500, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21296635

ABSTRACT

OBJECTIVE: To evaluate the clinical value of (18)F-FDG PET/CT in postoperative monitoring for patients with colorectal carcinoma. METHODS: 66 postoperative patients with colorectal carcinoma underwent whole-body FDG PET/CT. The final histopathological and formal clinical follow-up findings were used as gold standard to determine the sensitivity and specificity of FDG PET/CT and enhanced CT of the same periods. RESULTS: The sensitivity and specificity of FDG PET/CT in detecting recurrence are 96.30%, 94.87% (while enhanced CT are 70.37% and 87.18% respectively). The sensitivity and specificity in detecting metastasis are 95.35%, 82.61% (enhanced CT are 61.90%, 75.00%). SUVmax was significantly higher in malignant lesions [range 4.16-22.00, mean±standard deviation (x±s) 8.06±4.30] than in benign ones (range 1.18-6.25, x±s 2.82±1.02). CONCLUSION: At present, whole-body (18)F-FDG PET/CT is an advanced diagnostic imaging technique in detecting loco-regional recurrence and metastasis in postoperative patients with colorectal carcinoma for its higher sensitivity and specificity.


Subject(s)
Colorectal Neoplasms/diagnosis , Fluorodeoxyglucose F18 , Neoplasm Recurrence, Local/diagnosis , Positron-Emission Tomography , Tomography, X-Ray Computed , Adolescent , Adult , Aged , Bone Neoplasms/diagnosis , Bone Neoplasms/secondary , Bone Neoplasms/surgery , Colorectal Neoplasms/surgery , Female , Follow-Up Studies , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Lung Neoplasms/diagnosis , Lung Neoplasms/secondary , Lung Neoplasms/surgery , Lymphatic Metastasis , Male , Middle Aged , Monitoring, Physiologic , Neoplasm Recurrence, Local/surgery , Peritoneal Neoplasms/diagnosis , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/surgery , Postoperative Care , Prognosis , Radiopharmaceuticals , Sensitivity and Specificity , Young Adult
18.
Lung Cancer ; 73(3): 332-7, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21292341

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the prognostic significance of some metabolic parameters measured by (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in patients with small cell lung cancer (SCLC). METHODS: We retrospectively reviewed 98 patients with pathologically proven SCLC who underwent pre-treatment (18)F-FDG PET/CT. Metabolic tumor volume (MTV), integrated standardized uptake value (iSUV) and average SUV (SUV(mean)) of all malignant lesions, and maximum SUV (SUV(max)) of the primary tumor were measured by (18)F-FDG PET/CT. We determined the relationship between overall survival (OS) and progression free survival (PFS) and these PET metabolic parameters. RESULTS: The estimated median OS and PFS for the entire cohort were 16.7 months and 9.8 months. The patients with larger MTV had significantly shorter median OS (9.6 months vs 23.2 months, P<0.001) and PFS (6.9 months vs 15.5 months, P<0.001) than the patients with smaller MTV. On multivariate analysis, MTV, iSUV, tumor stage and LDH were the significantly prognostic factors with OS and PFS. SUV(max) did not show correlation with OS and PFS. In subgroup analysis, limited disease (LD) with larger MTV showed significantly shorter median OS and PFS than LD with smaller MTV. Extensive disease (ED) with larger MTV also had significantly shorter median OS and PFS than the same stage with smaller MTV. CONCLUSIONS: MTV and iSUV are important independent prognostic factors for survival in patients with SCLC. Either MTV or iSUV may identify subgroups of patients at higher risk of progression or death in both LD and ED SCLC.


Subject(s)
Fluorodeoxyglucose F18/metabolism , Lung Neoplasms/diagnosis , Positron-Emission Tomography , Small Cell Lung Carcinoma/diagnostic imaging , Tomography, Emission-Computed , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lung Neoplasms/physiopathology , Male , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Prognosis , Retrospective Studies , Small Cell Lung Carcinoma/mortality , Small Cell Lung Carcinoma/pathology , Small Cell Lung Carcinoma/physiopathology , Survival Analysis
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