Chemotherapy effect on myocardial fibrosis markers in patients with gynecologic cancer and low cardiovascular risk.

Background: Patients with gynecologic cancers experience side effects of chemotherapy cardiotoxicity. We aimed to quantify cardiac magnetic resonance (CMR) markers of myocardial fibrosis in patients with gynecologic cancer and low cardiovascular risk who undergo chemotherapy. Methods: This study is part of a registered clinical research. CMR T1 mapping was performed in patients with gynecologic cancer and low cardiovascular risk undergoing chemotherapy. The results were compared with those of age-matched healthy control subjects. Results: 68 patients (median age = 50 years) and 30 control subjects were included. The median number of chemotherapy cycles of patients was 9.0 (interquartile range [IQR] 3.3-17.0). Extracellular volume fraction (ECV) (27.2% ± 2.7% vs. 24.5% ± 1.7%, P < 0.001) and global longitudinal strain (-16.2% ± 2.8% vs. -17.4% ± 2.0%, P = 0.040) were higher in patients compared with controls. Patients with higher chemotherapy cycles (>6 cycles) (n=41) had significantly lower intracellular mass indexed (ICMi) compared with both patients with lower chemotherapy cycles (≤6 cycles) (n=27) (median 27.44 g/m2 [IQR 24.03-31.15 g/m2] vs. median 34.30 g/m2 [IQR 29.93-39.79 g/m2]; P = 0.002) and the control group (median 27.44 g/m2 [IQR 24.03-31.15 g/m2] vs. median 32.79 g/m2 [IQR 27.74-35.76 g/m2]; P = 0.002). Patients with two or more chemotherapy regimens had significantly lower ICMi compared with both patients with one chemotherapy regimen (27.45 ± 5.16 g/m2 vs. 33.32 ± 6.42 g/m2; P < 0.001) and the control group (27.45 ± 5.16 g/m2 vs. 33.02 ± 5.52 g/m2; P < 0.001). The number of chemotherapy cycles was associated with an increase in the ECV (Standard regression coefficient [ß] = 0.383, P = 0.014) and a decrease in the ICMi (ß = -0.349, P = 0.009). Conclusion: Patients with gynecologic cancer and low cardiovascular risk who undergo chemotherapy have diffuse extracellular volume expansion, which is obvious with the increase of chemotherapy cycles. Myocyte loss may be part of the mechanism in patients with a higher chemotherapy load. Clinical trial registration: http://www.chictr.org.cn, identifier ChiCTR-DDD-17013450.

Choriocarcinoma misdiagnosed as cerebral hemangioma: A case report.

BACKGROUND: Choriocarcinoma is a subtype of gestational trophoblastic disease, gestational trophoblastic neoplasia. Patients with brain metastasis are rare and information on the optimal treatment and patient outcome is limited. In order to improve the prognosis of this disease, accurate and timely treatments are very important for the patient of brain metastasis by choriocarcinoma. CASE SUMMARY: A 17-year-old unmarried girl was misdiagnosed with a cerebral hemangioma with intracranial hemorrhage in a local hospital after presentation with severe head pain. She underwent craniotomy three times for treatment. The pathological results of posterior intracranial hematoma showed choriocarcinoma, and the patient was diagnosed as choriocarcinoma (21 points in stage IV). After uterine artery embolization, etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine chemotherapy for 7 cycles, and whole brain radiotherapy, the patient achieved remission. She has been followed for 2 years with no signs of tumor recurrence. CONCLUSION: For female patients of childbearing age with an intracranial hematoma, the possibility of brain metastasis by choriocarcinoma should be considered. It is necessary to obtain a detailed history, including menstruation, beginning age of first sex, contraception, etc. The level of ß-human chorionic gonadotropin should be tested at the beginning, and a stratified treatment should be administered according to the International Federation of Gynecology and Obstetrics staging and World Health Organization prognostic scoring systems.

Folate-linked lipoplexes for short hairpin RNA targeting claudin-3 delivery in ovarian cancer xenografts.

Ovarian cancers highly overexpress folate receptor α (FRα) and claudin3 (CLDN3), both of which are associated with tumor progression and poor prognosis of patients. Downregulation of FRα and CLDN3 in ovarian cancer may suppress tumor growth and promote benign differentiation of tumor. In this study, F-P-LP/CLDN3, a FRα targeted liposome loading with short hairpin RNA (shRNA) targeting CLDN3 was prepared and the pharmaceutical properties were characterized. Then, the antitumor effect of F-P-LP/CLDN3 was studied in an in vivo model of advanced ovarian cancer. Compared with Control, F-P-LP/CLDN3 promoted benign differentiation of tumor and achieved about 90% tumor growth inhibition. In the meantime, malignant ascites production was completely inhibited, and tumor nodule number and tumor weight were significantly reduced (p<0.001). FRα and CLDN3 were downregulated together in tumor tissues treated by F-P-LP/CLDN3. The antitumor mechanisms were achieved by promoting tumor cell apoptosis, inhibiting tumor cell proliferation and reducing microvessel density. Finally, safety evaluation indicated that F-P-LP/CLDN3 was a safe formulation in intraperitoneally administered cancer therapy. We come to a conclusion that F-P-LP/CLDN3 is a potential targeting formulation for ovarian cancer gene therapy.

Different combination schedules of gemcitabine with endostar affect antitumor efficacy.

PURPOSE: Antiangiogenic drugs inhibit tumor growth by decreasing blood supply and causing transient "normalization" of the tumor vasculature, thereby improving the delivery of systemic chemotherapy. A higher dose of antiangiogenic drugs may lead to a more marked decrease in intratumoral blood flow but may concomitantly cause a decrease in delivery of chemotherapeutic agents. The purpose of this study was to define an optimal schedule for the combination of gemcitabine with a recombinant endostatin, endostar. METHODS: We evaluated the antitumor effects with different schedules of gemcitabine combined with or without endostar. The changes of vascular endothelial growth factor (VEGF) levels in tumor extracts and sera after gemcitabine treatment were examined. Endostar was also assessed for its abilities to inhibit the increase in VEGF levels. Apoptotic cells and microvessel density within tumor tissue were also examined. RESULTS: Endostar administered simultaneously with or following gemcitabine improved the inhibition of tumor growth, compared with gemcitabine alone. VEGF levels decreased immediately after gemcitabine treatment, but increased in the following several days. Endostar administered simultaneously with or following gemcitabine could inhibit the increase in VEGF levels, thereby cause a decreased vessel density and an increased apoptosis in tumor tissue. CONCLUSIONS: Our finding suggested that endostar given simultaneously with or following gemcitabine might be optimal to enhance the antitumor effect.

Comparative proteomic approach identifies PKM2 and cofilin-1 as potential diagnostic, prognostic and therapeutic targets for pulmonary adenocarcinoma.

Lung cancer is the leading cause of cancer-related death in the world. Non-small cell lung carcinomas (Non-SCLC) account for almost 80% of lung cancers, of which 40% were adenocarcinomas. For a better understanding of the molecular mechanisms behind the development and progression of lung cancer, particularly lung adenocarcinoma, we have used proteomics technology to search for candidate prognostic and therapeutic targets in pulmonary adenocarcinoma. The protein profile changes between human pulmonary adenocarcinoma tissue and paired surrounding normal tissue were analyzed using two-dimensional polyacrylamide gel electrophoresis (2-DE) based approach. Differentially expressed protein-spots were identified with ESI-Q-TOF MS/MS instruments. As a result, thirty two differentially expressed proteins (over 2-fold, p<0.05) were identified in pulmonary adenocarcinoma compared to normal tissues. Among them, two proteins (PKM2 and cofilin-1), significantly up-regulated in adenocarcinoma, were selected for detailed analysis. Immunohistochemical examination indicated that enhanced expression of PKM2 and cofilin-1 were correlated with the severity of epithelial dysplasia, as well as a relatively poor prognosis. Knockdown of PKM2 expression by RNA interference led to a significant suppression of cell growth and induction of apoptosis in pulmonary adenocarcinoma SPC-A1 cells in vitro, and tumor growth inhibition in vivo xenograft model (P<0.05). In addition, the shRNA expressing plasmid targeting cofilin-1 significantly inhibited tumor metastases and prolonged survival in LL/2 metastatic model. While additional works are needed to elucidate the biological significance and molecular mechanisms of these altered proteins identified in this study, PKM2 and cofilin-1 may serve as potential diagnostic and prognostic biomarkers, as well as therapeutic targets for pulmonary adenocarcinoma.

Comparative proteomic analysis of irinotecan-sensitive colorectal carcinoma cell line and its chemoresistant counterpart.

In this study, we used two-dimensional gel electrophoresis and MALDI-Q-TOF-MS/MS analysis to examine the global protein expression of a pair of colorectal carcinoma cell lines, SW620 and irinotecan-resistant SW620. Of the 30 spots identified as differentially expressed proteins (±over twofold, P<0.05) between the two cell lines, 26 spots (corresponding to 26 unique proteins) were positively identified by MALDI-Q-TOF-MS/MS analysis. These proteins could be grouped into main classes including metabolism (15.38%), cell SSproliferation/differentiation (11.53%), molecular chaperone (11.53%), mRNA splicing (11.53%), and so on. The proteins, which might be involved in the development of tumor drug resistance, such as α-enolase, cofilin, and thioredoxin-dependent peroxide 1, have been validated by western blot analysis and have been discussed. The proteins identified in this study may be useful in showing the mechanisms underlying irinotecan resistance.

Proteomic analysis of cell lines to identify the irinotecan resistance proteins.

Chemotherapeutic drug resistance is a frequent cause of treatment failure in colon cancer patients. Several mechanisms have been implicated in drug resistance. However, they are not sufficient to exhaustively account for this resistance emergence. In this study, two-dimensional gel electrophoresis (2-DE) and the PDQuest software analysis were applied to compare the differential expression of irinotecan-resistance-associated protein in human colon adenocarcinoma LoVo cells and irinotecan-resistant LoVo cells (LoVo/irinotecan). The differential protein dots were excised and analysed by ESI-Q-TOF mass spectrometry (MS). Fifteen proteins were identified, including eight proteins with decreased expression and seven proteins with increased expression. The identified known proteins included those that function in diverse biological processes such as cellular transcription, cell apoptosis, electron transport/redox regulation, cell proliferation/differentiation and retinol metabolism pathways. Identification of such proteins could allow improved understanding of the mechanisms leading to the acquisition of chemoresistance.