Adjuvant pembrolizumab versus high-dose interferon α-2b for Chinese patients with resected stage III melanoma: a retrospective cohort study.

Background Pembrolizumab has robust antitumor activity in advanced melanoma and has been approved for the treatment of melanoma in many countries. Adjuvant pembrolizumab was associated with longer recurrence-free survival (RFS) in patients with resected stage III melanoma. We herein report on the RFS outcomes of Chinese patients with resected stage III melanoma receiving adjuvant pembrolizumab in comparison to those receiving interferon α-2b (IFN-α-2b). Methods We retrospectively investigated the medical records of subjects with resected stage III melanoma with no in-transit metastases diagnosed who were treated at the Cancer Hospital of the University of Chinese Academy of Sciences and collected historical clinical data of patients receiving adjuvant IFN-α-2b therapy in our hospital. The RFS rates were evaluated using Kaplan-Meier curves, and the differences between the groups were tested using the log-rank test. Results A total of 29 patients receiving adjuvant pembrolizumab therapy and 27 patients receiving adjuvant IFN-α-2b therapy were enrolled. The median RFS was not reached (95% CI not estimable [NE]) in the pembrolizumab group and was 25 months in the IFN-α-2b group, and there was no significant difference in RFS between the pembrolizumab and IFN-α-2b groups (HR = 1.20, log-rank p = 0.75). There was no significant difference in RFS for acral melanoma between the pembrolizumab group and IFN-α-2b group (HR = 1.22, log-rank p = 0.79). For patients with IIIC or IIID melanoma, the RFS in the pembrolizumab group was also similar to that of the IFN-α-2b group (HR = 0.80, log-rank p = 0.47). The RFS for patients receiving pembrolizumab with programmed cell death ligand 1 (PD-L1)-positive tumors might tend to be longer than that for patients with PD-L1-negative tumors, but there was no significant difference between the groups (HR = 3.37, log-rank p = 0.17). High tumor mutational burden (TMB) did not reveal a trend to predict a longer RFS than low TMB in patients receiving pembrolizumab (HR = 1.63, log-rank p = 0.63). Grade 3-4 adverse events occurred in 6 (22.22%) of 27 patients in the IFN-α-2b group. Discontinuations attributed to adverse events (AEs) occurred in 2 patients treated with IFN-α-2b. Immune-related adverse events were observed in 5 (17.24%) patients in the pembrolizumab group. In the pembrolizumab group, grade 3-4 adverse events occurred in 2 (6.90%) patients, 1 of which required the discontinuation of a study drug and corticosteroid treatment. None of the patients discontinued treatment due to treatment-related or immune-mediated AEs. Conclusions Adjuvant pembrolizumab appeared to be as effective as IFN-α-2b in prolonging RFS in Chinese patients with resected stage III melanoma. Adjuvant pembrolizumab was associated with a lower rate of treatment-related AEs than IFN-α-2b. A prospective study is needed to confirm the clinical benefit of adjuvant pembrolizumab and determine dependable biomarkers.

The prognostic value of pretreatment tumor apparent diffusion coefficient values in nasopharyngeal carcinoma.

BACKGROUND: Diffusion-weighted MR imaging (DWI) has increasingly contributed to the management of nasopharyngeal carcinoma (NPC) patients. The objective of this paper was to explore the prognostic significance of apparent diffusion coefficient (ADC) values in 93 NPC patients. METHODS: This retrospective study included 93 newly diagnosed NPC patients. Pretreatment ADC values were determined and compared with patients' age, gender, alcohol intake, smoking, tumor volume, pathological type, tumor stage, and nodal stage. Using the Kaplan-Meier method, overall survival (OS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were calculated and the values compared between the low and high ADC groups. Multivariate analysis of ADC values and other 9 clinical parameters was performed using a Cox proportional hazards model to test the independent significance for OS, LRFS and DMFS. RESULTS: The mean ADC value for the initial nasopharyngeal tumors was 0.72 × 10-3 mm2/s (range: 0.48-0.97 × 10-3 mm2/s). There was no significant difference between pretreatment ADCs and patient' gender, age, smoking, alcohol intake, or tumor stage. A significant difference in the ADCs for different N stages (P = 0.022) and correlation with initial tumor volume (r = -0.26, P = 0.012) were observed. In comparison, the ADC value for undifferentiated carcinoma was lower than that for other 3 pathological types. With a median follow-up period of 50 months, the 3-year and 5-year OS rates were 88.2% and 83.3%, respectively, 3-year and 5-year LRFS rates were 93.5% and 93.3%, respectively, and 3-year and 5-year DMFS rates were 83.9% and 83.3%, respectively. Patients with tumor ADC values ≥0.72 × 10-3 mm2/s exhibited longer OS and LRFS periods compared with tumor ADC values <0.72 × 10-3 mm2/s, with P values 0.036 and 0.018, respectively. In addition, patients with deaths or recurrences or distant metastasis had significant lower ADC values than those without disease failures. According to a multivariate analysis using the Cox proportional hazard test, ADC values showed a significant correlation with OS (P = 0.0004), LRFS (P = 0.0009), and DMFS (P < 0.0001), respectively. CONCLUSIONS: Pretreatment tumor ADC values supposed to be a noninvasive important prognostic parameter for NPC.

Tangeretin inhibits neurodegeneration and attenuates inflammatory responses and behavioural deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease dementia in rats.

Our aim was to investigate whether tangeretin, a citrus flavonoid, was able to prevent neuroinflammation and improve dementia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced rodent model of Parkinson's disease (PD). MPTP-HCl was infused into the substantia nigra pars compacta of male Sprague-Dawley rats. Tangeretin (50, 100 or 200 mg/kg body weight) was administered orally starting 3 days prior to MPTP injection and was continued for 20 days following injection. MPTP-lesioned rats revealed motor dysfunction in bar test and rota rod tests. Deficits in working memory and object recognition function were also observed following MPTP induction. Tangeretin treatment significantly attenuated the memory deficits and improved motor functions and cognition. Immunohistochemical analysis reveals the protective effects of tangeretin against MPTP lesion-induced dopaminergic degeneration and hippocampal neuronal loss. Tangeretin reduced expression of inflammatory mediators-COX-2, iNOS-as well reduced the levels of cytokines-interleukins (IL)-IL-1ß, IL-6 and IL-2. The experimental data suggest tangeretin as an effective candidate drug with potential for prevention and treatment of neuroinflammation and dementia associated with PD.

The role of FERMT2 in the tumor microenvironment and immunotherapy in pan-cancer using comprehensive single-cell and bulk sequencing.

FERMT2 has been identified as a participant in integrin-linked kinase signaling pathways, influencing epithelial-mesenchymal transition and thereby affecting tumor initiation, progression, and invasion. While the character of FERMT2 in the tumor microenvironment (TME) as well as its implications for immunotherapy remain unclear. Thus, we conducted a comprehensive analysis to assess the prognostic significance of FERMT2 using Kaplan-Meier analysis. In addition, we employed enrichment analysis to uncover potential underlying molecular mechanisms. Using "Immunedeconv" package, we evaluated the immune characteristics of FERMT2 within TME. Furthermore, we determined the expression levels of FERMT2 in various cell types within TME, based on single-cell sequencing data. To confirm the co-expression of FERMT2 and markers of cancer-associated fibroblasts (CAFs), we performed multiplex immunofluorescence staining on tissue paraffin sections across various cancer types. Our analysis disclosed a significant correlation between elevated FERMT2 expression and unfavorable prognosis in specific cancer types. Furthermore, we identified a strong correlation between FERMT2 expression and diverse immune-related factors, including immune checkpoint molecules, immune cell infiltration, microsatellite instability (MSI), and tumor mutational burden (TMB). Additionally, there was a significant correlation between FERMT2 expression and immune-related pathways, particularly those associated with activating, migrating, and promoting the growth of fibroblasts in diverse cancer types. Interestingly, we observed consistent co-expression of FERMT2 in both malignant tumor cells and stromal cells, particularly within CAFs. Notably, our findings also indicated that FERMT2, in particular, exhibited elevated expression levels within tumor tissues and co-expressed with α-SMA in CAFs based on the multiplex immunofluorescence staining results.

Correlation analysis of preoperative serum alpha-fetoprotein (AFP) level and prognosis of hepatocellular carcinoma (HCC) after hepatectomy.

BACKGROUND: To investigate the prediction value of preoperative serum alpha-fetoprotein (AFP) level for the prognosis of hepatocellular carcinoma (HCC), by comparing pathological characteristics, recurrence rate and survival rate after hepatectomy. METHODS: 108 cases of HCC patients who received liver resection in our hospital from 2005 to 2011 were enrolled in this study. According to preoperative serum AFP level, the patients were divided into AFP ≤ 20 ng/mL group, AFP 20 to 400 ng/mL group and AFP > 400 ng/mL group, and the clinicopathological and cytopathological features were compared. All the patients were followed up for 24 months, the postoperative recurrence rates and survival rates were compared and analyzed, and the risk factors for HCC postoperative survival rate were studied by multifactor regression analysis. RESULTS: Of the 108 cases of HCC patients, there were 42 cases in AFP ≤20 ng/mL group, 28 cases in AFP 20-400 ng/mL group and 39 cases in AFP > 400 ng/mL group. It was shown that cell differentiation degrees (χ² = 20.198, P = 0.000) and microvascular invasion rates (χ² = 20.358, P = 0.000) were significantly different among the three groups. The AFP ≤ 20 ng/mL group showed higher cell differentiation degrees and significantly lower microvascular invasion rates compared to the other groups (P < 0.05). The follow-up data showed that postoperative 2-year recurrence rate (χ² = 6.164, P = 0.046), 18-month survival rate (χ² = 7.647, P = 0.022) and 24-month survival rate (χ² = 6.725, P = 0.035) of the three groups were significantly different, and we found that the AFP ≤ 20 ng/mL group had lower postoperative 2-year recurrence rate, and higher 18-month survival rate and 24-month survival rate than the other two groups (P <0.05). Multiple logistic regression analysis indicated that tumor diameter (≥ 5 cm) and preoperative serum AFP level (> 400 ng/mL) were closely correlated with HCC postoperative survival rate (P <0.05). CONCLUSIONS: It is shown that preoperative serum AFP level has considerable predictive value for the malignant feature and prognosis of HCC. It is suggested that HCC patients with no contraindication of operation and serum AFP ≤ 20 ng/mL can benefit most from primary treatment of hepatectomy. While HCC patients with serum AFP higher than 20 ng/mL need comprehensive therapy besides surgical resection and close follow up.

Indocyanine green clearance in evaluating the recovery of liver reserve function after superselective transarterial chemoembolization.

Transarterial chemoembolization (TACE) may ravage normal liver tissues apart from the neoplastic nodules which offset the anti-tumor effect. This study aimed to evaluate the recovery of liver reserve function (LRF) after TACE by indocyanine green (ICG) clearance test and other routine liver function tests. Forty-six newly diagnosed HCC patients who had undergone TACE as the initial treatment from January 2011 to January 2012 were enrolled in this study. The effects of age, basic ICG clearance rate and interval time between two assessments on the recovery of LRF were analyzed. We found that ICG retention rate at the 15 minutes (ICGR15) was significantly increased after TACE (12.3+/-8.1% vs 16.8+/-12.1%, P<0.01) in all the 46 patients. In particular, the ICGR15 value was increased in older patients (age>55 years, 20.3+/-12.5% vs 13.7+/-7.2%, P<0.01). The interval of ICG test also affected the ICGR15 value (≤47 days, 17.8+/-11.4% after vs 12.1+/-7.1% before TACE, P<0.01). Our data suggested that TACE decreased LRF, especially in older patients. ICG test was more sensitive to evaluate the recovery of LRF after TACE than the Child-Pugh grade and routine liver function tests.

Prognostic significance of solitary lymph node metastasis in patients with squamous cell carcinoma of middle thoracic esophagus.

BACKGROUND: The aim of this study is to compare clinical outcomes between patients with solitary lymph node metastasis and node-negative (N0) patients in squamous cell carcinoma of the middle thoracic esophagus. METHODS: A series of 135 patients with squamous cell carcinoma of the middle thoracic esophagus were retrospectively investigated. There were 33 patients with solitary lymph node metastasis and 102 N0 patients. Skip metastasis in 33 patients with solitary lymph node metastasis was defined according to three criteria: Japanese Society for Esophageal Disease (JSED), American Joint Commission on Cancer (AJCC), and the anatomical compartment. RESULTS: In 33 patients with solitary lymph node metastasis, skip metastasis was shown in 13, 23, and 8 patients according JSED, AJCC and anatomical compartment respectively. The 5-year survival rates for N0 patients and patients with solitary lymph node metastasis were 58% and 32% respectively (P =0.008). Multivariate analysis revealed that skip metastasis was not an independent prognostic factor. CONCLUSIONS: For patients with middle thoracic esophageal squamous cell carcinoma, solitary lymph node metastasis has a negative impact on survival compared with N0 disease; skip metastasis, however, is comparable to N0 diseases in predicting prognosis.

Identification of Long Noncoding RNAs Associated With the Clinicopathological Features of Papillary Thyroid Carcinoma Complicated With Hashimoto's Thyroiditis.

Long noncoding RNAs (lncRNAs) play a significant role in cancer biology. This study aimed to determine the roles of lncRNAs in establishing the differences in clinical features between patients with papillary thyroid carcinoma (PTC) without Hashimoto's thyroiditis (HT) and patients with PTC and HT. In the present study, we detected the differentially expressed lncRNAs between tumor tissues of patients with PTC with or without HT through lncRNA microarrays. The data were verified and analyzed through qRT-PCR, cell viability, cell cycle and bioinformatics analyses. We found that 1031 lncRNAs and 1338 mRNAs were abnormally expressed in 5 tissue samples of PTC complicated with HT [PTC/HT (+)] compared with 5 samples of PTC without HT [PTC/HT (-)]. Gene Ontology and pathway analyses of the mRNAs suggested that several biological processes and pathways, particularly immune system processes, were induced in the PTC/HT (+) tissues. Twenty lncRNAs were verified in 31 PTC/HT (+) and 64 PTC/HT (-) specimens by qRT-PCR, and the results were consistent with the microarray data. Specifically, ENST00000452578, a downregulated lncRNA in PTC/HT(+), was negatively correlated with the tumor size. Cell viability assays revealed that ENST00000452578 could inhibit cell proliferation. Our results indicate that lncRNAs and mRNAs play an important role in establishing the different clinical characteristics between patients with PTC/HT(+) and patients with PTC/HT(-), and might provide new insights from the perspective of RNA for obtaining a further understanding of the clinical features related to PTC with HT.

Malignant transformation of biliary adenofibroma combined with benign lymphadenopathy mimicking advanced liver carcinoma: A case report.

BACKGROUND: Biliary adenofibromas (BAFs) are rare primary hepatic neoplasms, some of which can potentially undergo malignant transformation. Here, we describe a rare case of malignant transformation of BAF. CASE SUMMARY: A 51-year-old female was referred to our hospital with epigastric pain. Computed tomography showed a solitary liver mass combined with the enlargement of multiple mediastinal and cervical lymph nodes, clinically mimicking a liver carcinoma with extensive lymph node metastasis. However, core needle biopsy suggested BAF with malignant transformation. Finally, the patient underwent curative resection of the neoplasm and was recurrence-free for 12 mo. CONCLUSION: Our case serves as an example of a rare manifestation of BAF. Our report and the previously published experience, reinforce that curative resection should be considered the primary treatment for BAFs with malignant transformation, leading to a favorable prognosis.

Radiofrequency ablation, heat shock protein 70 and potential anti-tumor immunity in hepatic and pancreatic cancers: a minireview.

BACKGROUND: Radiofrequency ablation (RFA) is a minimally invasive surgical procedure which has widespread popularity in the treatment of hepatic and pancreatic cancers. Increased evidence indicates that RFA stimulates anti-tumor immunity, possibly through the induction heat shock protein 70 (HSP70) expression. HSP70 has the capacity to affect the immunogenicity of tumor cells, to chaperone antigenic peptides and deliver these into antigen presentation pathways within antigen-presenting cells, and to activate and regulate innate and adaptive immunity, which makes it useful in immunotherapeutic strategies for the treatment of cancers. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1991-2010) on anti-tumor immunity, heat shock protein 70, radiofrequency ablation, hepatic cancer, pancreatic cancer, and other related subjects. RESULTS: RFA has an increasing application in the surgical treatment of hepatic and pancreatic cancers. Increased evidence indicates that RFA can induce the expression of HSP70 which possesses properties that enable it to influence a variety of immunological processes. Tumor-derived HSP70 is regarded as a potent adjuvant facilitating presentation of tumor antigens and induction of anti-tumor immunity. CONCLUSIONS: This review addresses the potential association of RFA, HSP70, and anti-tumor immunity in treatment of hepatic and pancreatic cancers. To establish direct evidence of a potential association of RFA, HSP70, and anti-tumor immunity in hepatic and pancreatic cancers, further investigations should be conducted.

[Comparison between analysis of HER2 gene and chromosome 17 in breast cancer by dual-probe chromogenic in situ hybridization and fluorescence in situ hybridization].

OBJECTIVE: To evaluate the application of dual-probe chromogenic in situ hybridization (dual-probe CISH) in analysis of HER2 gene status of breast cancer patients by comparison with fluorescence in situ hybridization (FISH). The potential impact of chromosome 17 polysomy in the determination of HER2 status was also studied. METHODS: One hundred and forty-six cases of paraffin-embedded breast cancer tissues were retrieved. Analysis of HER2 gene and chromosome 17 copy numbers using CE-approved commercial kits of dual-probe FISH (for 146 cases) and dual-probe CISH (for 73 cases) were carried out. The results were interpreted according to ASCO/CAP, 2007 either HER2 gene copy number or the ratio of HER2/centromere 17 (CEN17). RESULTS: Of the 73 cases analyzed by both FISH and dual-probe CISH, the concordance rates for negative and positive results was 91.7% (33/36) and 97.4% (37/38) respectively, while the overall concordance rate between the two methods was 95.9% (70/73). Of the 146 cases analyzed by FISH, 13 cases were interpreted as equivocal if only HER2 copies were counted, compared with 8 equivocal cases by calculating the ratio of HER2/CEN 17. Moreover, 3 cases (4.8%) of the 63 HER2-positive cases determined by HER2 copies turned out to be HER2-negative when determined by the ratio of HER2/CEN 17; while using dual-probe CISH, 1 (3.0%) of the 33 positive cases turned out to be negative. In addition, when using FISH, there were more chromosome 17 polysomy cases (63.5%, 40/63) in the HER2-positive subgroup than HER2-negative subgroup (37.3%, 28/75) (P = 0.002). CONCLUSIONS: Dual-probe CISH can achieve similar results as compared to FISH, indicating that this technology is a reliable alternative to FISH in HER2 testing. The accuracy can further be improved when HER2 and chromosome 17 are simultaneously tested and counted.

Combined High Resistin and EGFR Expression Predicts a Poor Prognosis in Breast Cancer.

Elevated levels of resistin and epidermal growth factor receptor (EGFR) facilitate the development of breast cancer, although there are no reports of any correlation between these proteins. This study analyzed 392 human breast cancer tissue specimens and 42 samples of adjacent normal tissue. Rates of positive and strongly positive resistin expression were significantly higher in breast cancer tissue than in the adjacent nontumor tissue (83.2% vs. 23.8% and 20.9% vs. 0.0%, respectively; P < 0.001 for both comparisons). Positive resistin expression was significantly associated with tumor size, grade, stage, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, and molecular classification; strongly positive resistin expression was associated with tumor grade, ER, PR, HER2 status, and molecular classification. Significantly positive correlations were observed between positive and strongly positive resistin expression and corresponding levels of EGFR expression. Relapse-free and overall survival was worse for patients with high levels of both proteins than for those with high levels of only one protein or normal levels of both proteins. Our evidence suggests that combined high levels of resistin and EGFR expression correlate with survival in patients with breast cancer.

Molecular fingerprint of precancerous lesions in breast atypical hyperplasia.

OBJECTIVE: To identify atypical hyperplasia (AH) of the breast by shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS), and to explore the molecular fingerprinting characteristics of breast AH. METHODS: Breast hyperplasia was studied in 11 hospitals across China from January 2015 to December 2016. All patients completed questionnaires on women's health. The differences between patients with and without breast AH were compared. AH breast lesions were detected by Raman spectroscopy followed by the SHINERS technique. RESULTS: There were no significant differences in clinical features and risk-related factors between patients with breast AH (n = 37) and the control group (n = 2576). Fifteen cases of breast AH lesions were detected by Raman spectroscopy. The main different Raman peaks in patients with AH appeared at 880, 1001, 1086, 1156, 1260, and 1610 cm-1, attributed to the different vibrational modes of nucleic acids, ß-carotene, and proteins. Shell-isolated nanoparticles had different enhancement effects on the nucleic acid, protein, and lipid components in AH. CONCLUSION: Raman spectroscopy can detect characteristic molecular changes in breast AH lesions, and may thus be useful for the non-invasive early diagnosis and for investigating the mechanism of tumorigenesis in patients with breast AH.

Fossa trochanterica of the proximal femur in rabbits: an anatomic structure for potential misinterpretation on magnetic resonance images.

BACKGROUND: Magnetic resonance imaging (MRI) has been increasingly used as an investigational tool for assessing the structure and function of animal skeletal disease models. However, to date, MRI tomographic knowledge of laboratory animal skeletal anatomy and pathology remains limited. PURPOSE: To demonstrate that fossa trochanterica of the proximal femur in rabbits can potentially be misinterpreted as a bone lesion on MR images. MATERIAL AND METHODS: Twenty 28-30-week-old male New Zealand white rabbits were used in the study. Corticosteroid-induced osteonecrosis induction was carried out with a combined administration of lipopolysaccharide and methylprednisolone. In this animal model, it is known that osteonecrosis commonly occurs in the proximal femur. MRI at 1.5 T was performed before osteonecrosis induction, and at 1 and 2 weeks post-osteonecrosis induction. For anatomical imaging of the proximal femur, coronal sectional images were obtained to align the femoral head, neck, and proximal shaft in a single plane. Volumetric computed tomography (CT) comprised continuous axial acquisitions through the bilateral hip joints and femurs and was performed on one age- and sex-matched New Zealand white rabbit to correlate MRI anatomical findings. RESULTS: In 30% of the acquired normal data sets, a low-signal area surrounded by high-signal bone marrow was observed slightly distal to the femoral head and medial to the third trochanter. This dark, low-signal area resembled an osteonecrosis lesion on MR images. Volumetric CT clarified that the low MR signal was due to the deep fossa trochanterica structure in the rabbit proximal femur. CONCLUSION: Improved understanding of the cross-sectional anatomy of the fossa trochanterica in the rabbit proximal femur will prevent misinterpretation as a bone lesion on MR images.

Pitfalls in interpreting rat knee joint magnetic resonance images and their histological correlation.

BACKGROUND: Magnetic resonance (MR) imaging has been increasingly used as an investigational tool for assessing the structure and function of animal joint disease models, while to date MR tomographic knowledge of laboratory animal skeletal microanatomy remains limited. PURPOSE: To describe pitfalls in interpreting rat knee joint MR images and their histological correlation. MATERIAL AND METHODS: MR scans of the right knee of five 3-month-old Sprague-Dawley (SD) rats were carried out using a 4.7T magnet, using a fat-suppressed three-dimensional (3D) gradient echo sequence with a spatial resolution of 59 x 117 x 234 microm. Histology assessment with hematoxylin and eosin staining and Safranin O staining was carried out in the five 3-month-old SD rats and two SD rats of 1 month and 6 months old, respectively. MR images were analyzed by a radiologist, and histology data were assessed by a radiologist and a pathologist. RESULTS: Though the MR images were acquired in normal rats, many signs unfamiliar to radiologists were noted, including notch-like bright signal areas in the epiphysis, gray signal areas in the epiphysis, and fuzzy joint surface of the epiphysis of the femur and tibia. Detailed inspection of the histology specimen showed more unfamiliar features of rat knee microanatomy, including curvy or dipped surface of the femur/tibia epiphysis, areas composed of a mixture of cartilage and bone components, normal notch structure, cyst-like structure, and cavity between cortical lamellae under the joint cartilage. CONCLUSION: There are a number of normal microstructures of the rat knee joint that can be potentially misinterpreted as arthritic changes on MR images. Recognizing these rat knee microstructures can help correct image reading during biomedical research.

Combined use of chemotherapeutics and oncolytic adenovirus in treatment of AFP-expressing hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) which is always refractory to most chemotherapeutic agents may result in poor survival of patients with advanced HCC. Oncolytic adenovirus is a new form for cancer gene therapy via its ability to replicate and kill tumor cells in a tumor-specific manner. In order to eradicate tumors effectively, the combination of chemotherapeutic agents and oncolytic adenovirus has been considered. This study aimed to systematically analyze the possibility of synergistic cytotoxicity of oncolytic adenoviruses in combination with chemotherapeutic agents. METHODS: Several types of human HCC cell lines were used to determine the specificity and cytotoxicity of oncolytic adenovirus Ad5-HC and Ad5-AFP (IRES) by measuring cell viability in vitro and antitumor efficiency in vivo. The cytotoxicity of Ad5-HC and Ad5-AFP (IRES) combined with chemotherapeutic agents were also assessed by the methyl thiazolyl tetrazolium assay. RESULTS: Both Ad5-HC and Ad5-AFP (IRES) were significantly cytotoxic to HCC cells with great specificity in vitro and in vivo. The combination of oncolytic adenovirus with 5-FU, doxorubicin, and paclitaxel was synergistically effective for the killing of HCC cells. CONCLUSIONS: These data suggest that oncolytic adenovirus sensitize tumors to chemotherapy and the combination therapy of chemotherapeutic agents and oncolytic adenovirus has an enhanced antitumor effect on HCC cells.

[Multifocal papillary thyroid carcinoma: clinical analysis of 168 cases].

OBJECTIVE: To investigate the clinical features and treatment of multifocal papillary thyroid carcinoma (PTC). METHODS: A retrospective survey was carried out in 648 patients with PTC who underwent surgery from January 1997 to December 2006. One hundred and sixty-eight cases of the patients presented with multiple tumor masses (> or = 2). The risk factors, including sex of the patients, age at diagnosis, family history of thyroid tumor, multiplicity and bilaterality of tumor, extra-thyroidal extension, lymph node involvement and other were analyzed between solitary PTC and multifocal PTC group. RESULTS: The mean age of the patients was 42 years (range, 14 - 78 years), included 49 male and 119 female. Tumor foci were found in both thyroid lobes in 117 cases (69.6%). Patients with multifocal PTC were characterized by a higher ratio of male (P = 0.004), family history of thyroid tumor (P = 0.031), neck lymph node metastasis (P = 0.008) and extra-thyroidal extension (P = 0.001). However, solitary PTC tended to be with a higher rate of benign goiters in pathologic examination. In multifocal PTC group, male, neck lymphadenectasis, > or = 3 tumor masses or bilaterality of tumor tended to presented with larger tumor, more neck lymph node metastasis and extra-thyroidal extension; And a less malignant tumor in the cases detected with benign goiters in histological examination. By the end of 2007, 164 cases (97.6%) completed follow-up with a mean period of 46.1 months (range, 2 - 127 months), 5 died in the meantime. One patient has been followed-up for 16 months for suspect of lung metastases by chest X-ray. Recurrence occurred in 8 patients and were re-resected, 2 in remnant thyroid and 6 in neck lymph nodes. The overall 1-, 2-, 5-, and 10-year survival rate was 98.2%, 97.4%, 96.5% and 96.5%, respectively. American Joint Committee on Cancer (AJCC) stage was associated with prognosis significantly (chi(2) = 168.832, P = 0.000). CONCLUSIONS: Multifocus is one of the clinical features of PTC and is more malignant than solitary PTC. Total thyroidectomy with central compartment neck dissection could be standard treatment. Lateral nodal dissection is not necessary except for the cases with lymph node metastasis. AJCC stage is still the best prognostic factor.

Estrogen receptor alpha variant ERalpha46 mediates growth inhibition and apoptosis of human HT-29 colon adenocarcinoma cells in the presence of 17beta-oestradiol.

BACKGROUND: Estrogen is involved in suppression of colon cancer development and exerts its function via estrogen receptors alpha and beta (ERalpha, ERbeta). The recently identified ERalpha46 resulted from exon 1-deletion from the 66-kDa full length form of ERalpha66 is devoid of the transactivation domain AF-1, whose function remains largely unknown. METHODS: In this study, we compared the expression of ERalpha46 mRNA in 32 normal colorectal tissues and their matched colorectal cancer tissues by real-time quantitative polymerase chain reaction (PCR). Human colon adenocarcinoma cell HT-29, that has low endogenous expression of ERalpha46, was transfected with ERalpha46-expression vector; methyl thiazolyl tetrazolium (MTT) assay, flow cytometry, DNA fragmentation and TUNEL staining were used to evaluate the proliferation and apoptosis status of the cells in the presence of 17beta-oestradiol. RESULTS: Higher ERalpha46 mRNA levels were observed in normal colorectal tissues than in the corresponding cancer tissues. ERalpha46-transfected cells showed a significantly decreased growth rate than control cells and an accumulation of cells in the G(0/1) phase and a reduced proportion of cells in G(2)/M phase after exposed to 10(-8) mol/L 17beta-oestradiol. There were also more positive TUNEL stained cells in ERalpha46-transfected cells than the control cells in the presence of 17beta-oestradiol (P < 0.05). CONCLUSIONS: These data suggest that ERalpha46 may be involved in the development and/or progression of colorectal cancer via mediating growth inhibition and apoptosis of cancer cells in the presence of 17beta-oestradiol.

BRCA1/2 associated hereditary breast cancer.

Breast cancer is one of the leading causes of death in women today. Some of the patients are hereditary, with a large proportion characterized by mutation in BRCA1 and/or BRCA2 genes. In this review, we provide an overview of these two genes, focusing on their relationship with hereditary breast cancers. BRCA1/2 associated hereditary breast cancers have unique features that differ from the general breast cancers, including alterations in cellular molecules, pathological bases, biological behavior, and a different prevention strategy. But the outcome of BRCA1/2 associated hereditary breast cancers still remains controversial; further studies are needed to elucidate the nature of BRCA1/2 associated hereditary breast cancers.

Apoptosis induced by preoperative oral 5'-DFUR administration in gastric adenocarcinoma and its mechanism of action.

AIM: To study the apoptosis induced by preoperative oral 5'-DFUR administration in gastric adenocarcinoma and its mechanism of action. METHODS: Sixty gastric cancer patients were divided randomly into three groups (20 each group) before operation: group one:5'-DFUR oral administration at the dose of 800-1200 mg/d for 3 - 5 d, group two: 500 mg 5-FU + 200 mg/d CF by venous drip for 3 - 5 d,group three (control group). One or two days after chemotherapy, the patients were operated. Fas/FasL,PD-ECGF and PCNA were examined by immunohistochemistry and apoptotic tumor cells were detected by in situ TUNEL method. Fifty-four patients received gastrectomy, including 12 palliative resections and 42 radical resections. Six patients were excluded. Finally 18 cases in 5'-DFUR group, 16 cases in CF+5-FU group, and 20 cases in control group were analyzed. RESULTS: There was no significant difference in patient mean age, gender, white blood cell count, haematoglobin (HB),thromboplastin, perioperative complication incidence, radical or palliation resection, invasion depth (T), lymphonode involvement (N),metastasis (M) and TNM staging among the three groups. However,the PCNA index (PI) in 5'-DFUR group (40.51+/-12.62) and 5-FU+CF group (41.12+/-15.26) was significantly lower than that in control group (58.33+/-15.69) (F=9.083, P=0.000). The apoptotic index (AI) in 5'-DFUR group (14.39+/-9.49) and 5-FU+CF group (14.11+/-9.68)was significantly higher than that in control group (6.88+/-7.37) (F=4.409, P=0.017).The expression rates of Fas and FasL in group one and group three were 66.7% (12/18) and 50% (9/18), 43.8% (7/16) and 81.3% (13/16), 45.0% (9/20) and 85% (17/20), respectively. The expression rate of FasL in 5'-DFUR group was significantly lower than that in the other two groups (chi2=6.708, P=0.035). Meanwhile, the expression rate of PD-ECGF was significantly lower in 5'-DFUR group (4/18,28.6%) than in CF+5-FU group(9/16,56.3%)and control group (13/20,65.0%) (chi2=7.542, P=0.023). The frequency of Fas expression was significantly correlated with palliative or radical resection (chi2=7.651, P=0.006), invasion depth (chi2=8.927, P=0.003), lymphatic spread (chi2=4.488, P=0.034) and UICC stages (chi2=8.063, P=0.045) respectively. By the end of March 2005,45 patients were followed up. The 0.5-, 1-, 2-, 3-year survival rates were 96%,73%,60%,48%, respectively, which were related with T, N, M and Fas expression, but not with PD-ECGF and FasL expression. CONCLUSION: Preoperative oral 5'-DFUR administration may induce apoptosis of gastric carcinoma cells and decrease tumor cell proliferation index,but cannot improve the prognosis of patients with gastric cancer.Down-regulation of FasL and PD-ECGF expression mediated by 5'-DFUR may be one of its anti-cancer mechanisms.Fas expression correlates with the progression of gastric carcinoma and may be an effective prognostic factor.