Pivotal Role of GSTO2 in Ferroptotic Neuronal Injury After Intracerebral Hemorrhage.

Previous research has found that an adaptive response to ferroptosis involving glutathione peroxidase 4 (GPX4) is triggered after intracerebral hemorrhage. However, little is known about the mechanisms underlying adaptive responses to ferroptosis. To explore the mechanisms underlying adaptive responses to ferroptosis after intracerebral hemorrhage, we used hemin-treated HT22 cells to mimic brain injury after hemorrhagic stroke in vitro to evaluate the antioxidant enzymes and performed bioinformatics analysis based on the mRNA sequencing data. Further, we determined the expression of GSTO2 in hemin-treated hippocampal neurons and in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH) by using Western blot. After hemin treatment, the antioxidant enzymes GPX4, Nrf2, and glutathione (GSH) were upregulated, suggesting that an adaptive response to ferroptosis was triggered. Furthermore, we performed mRNA sequencing to explore the underlying mechanism, and the results showed that 2234 genes were differentially expressed. Among these, ten genes related to ferroptosis (Acsl1, Ftl1, Gclc, Gclm, Hmox1, Map1lc3b, Slc7a11, Slc40a1, Tfrc, and Slc39a14) were altered after hemin treatment. In addition, analysis of the data retrieved from the GO database for the ten targeted genes showed that 20 items on biological processes, 17 items on cellular components, and 19 items on molecular functions were significantly enriched. Based on the GO data, we performed GSEA and found that the glutathione metabolic process was significantly enriched in the hemin phenotype. Notably, the expression of glutathione S-transferase omega (GSTO2), which is involved in glutathione metabolism, was decreased after hemin treatment, and overexpression of Gsto2 decreased lipid reactive oxygen species level in hemin-exposed HT22 cells. In addition, the expression of GSTO2 was also decreased in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH). The decreased expression of GSTO2 in the glutathione metabolic process may be involved in ferroptotic neuronal injury following hemorrhagic stroke.

Large-scale bulk RNA-seq analysis defines immune evasion mechanism related to mast cell in gliomas.

Accumulating evidence has demonstrated that the immune cells have an emerging role in controlling anti-tumor immune responses and tumor progression. The comprehensive role of mast cell in glioma has not been illustrated yet. In this study, 1,991 diffuse glioma samples were collected from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). xCell algorithm was employed to define the mast cell-related genes. Based on mast cell-related genes, gliomas were divided into two clusters with distinct clinical and immunological characteristics. The survival probability of cluster 1 was significantly lower than that of cluster 2 in the TCGA dataset, three CGGA datasets, and the Xiangya cohort. Meanwhile, the hypoxic and metabolic pathways were active in cluster 1, which were beneficial to the proliferation of tumor cells. A potent prognostic model based on mast cell was constructed. Via machine learning, DRG2 was screened out as a characteristic gene, which was demonstrated to predict treatment response and predict survival outcome in the Xiangya cohort. In conclusion, mast cells could be used as a potential effective prognostic factor for gliomas.

An immediate postoperative response to therapy assessment can help avoid unnecessary RAI therapy.

Background: Radioiodine (RAI) therapy plays a vital role in the postoperative treatment of differentiated thyroid cancer (DTC) patients underwent total thyroidectomy (TT). However, even in the presence of capsular invasion and lymph node metastasis prognosis can be excellent and a postoperative RAI treatment might not be necessary for all patients. Therefore, this study explored the criteria for avoiding unnecessary RAI therapy in these patients. Method: We applied response to therapy assessment immediately after surgery and prospectively recruited 179 excellent or indeterminate response DTC patients with capsular invasion and/or LNM who underwent TT without RAI therapy. During the follow-up, thyroglobulin (Tg), thyroglobulin antibody (TgAb) levels, and cervical ultrasonography were collected and analyzed. Disease-free survival (DFS) was calculated using the Kaplan-Meier method. In addition, response to therapy assessments was performed on patients during each follow-up. Results: The mean follow-up period was 29.85 ± 17.44 months, and the 3- and 5-year DFS for all the patients was 99.3% in each. At the last follow-up, 165 (92.2%) patients had excellent responses, while 12 (6.7%) had an indeterminate response, and one (0.6%) each had biochemical and incomplete responses. No significant difference was observed in response to therapy between the subgroups of LNM and tumor invasion (P>0.05). For patients with capsular invasion and a number of metastatic lymph nodes ≤5 and >5, the proportions of recorded excellent responses were 95.9%, 91.0%, and 85.7%, respectively. Better responses were observed in females (excellent response: 95.5%, P=0.023), patients with stimulated Tg (s-Tg) ≤1ng/ml (excellent response: 100%, P<0.001), s-Tg ≤ 2ng/ml (excellent response: 98.4%, P<0.001), and excellent response for the immediate postoperative assessment (excellent response: 98.5%, P=0.004). Conclusions: The current study suggested that the response to therapy assessment immediately applied postoperatively could help avoid unnecessary RAI therapy among DTC patients with capsular invasion and/or LNM. Moreover, excellent response patients and patients with indeterminate response and s-Tg ≤ 2ng/ml could be managed without RAI therapy.

Genetic analysis combined with 3D-printing assistant surgery in diagnosis and treatment for an X-linked hypophosphatemia patient.

BACKGROUND: Hypophosphatemia is mainly characterized by hypophosphatemia and a low level of 1alpha,25-Dihydroxyvitamin D2 (1,25-(OH)2 D2) and/or 1alpha,25-Dihydroxyvitamin D3 (1,25-(OH)2 D3) in the blood. Previous studies have demonstrated that variants in PHEX and FGF23 are primarily responsible for this disease. Although patients with variants of these two genes share almost the same symptoms, they exhibit the different hereditary pattern, X-link dominant and autosome dominant, respectively. Three-dimensional (3D) printing is a method which can accurately reconstruct physical objects, and its applications in orthopedics can contribute to realizing a more accurate surgical performance and a better outcome. METHODS: An X-linked hypophosphatemia (XLH) family was recruited, with four patients across three generations. We screened candidate genes and filtered a duplication variant in PHEX. Variant analysis and co-segregation confirmation were then performed. Before the operation of our patient, a digital model of our patient's leg had been rebuilt upon the CT scan data, and a polylactic acid (PLA) model had been 3D-printed. RESULTS: A novel duplication PHEX variant c.574dupG (p.A192GfsX20) was identified in a family with XLH. Its pathogenicity was confirmed by the co-segregation assay and online bioinformatics database. The preoperative plan was made with the help of the PLA model. Then, arch osteotomy and transverse osteotomy were performed under the guidance of the previous simulation. The appearance of the surgical-intervened leg was satisfactory. CONCLUSIONS: This study identified a novel PHEX variant and showed that 3D printing tech is a very promising approach for corrective osteotomies.

Survival prognostic factors for differentiated thyroid cancer patients with pulmonary metastases: A systematic review and meta-analysis.

Background: The prognostic factors for differentiated thyroid cancer (DTC) patients with pulmonary metastases (PM) remain scantly identified and analyzed. Therefore, this systematic review and meta-analysis were performed to identify and summarize the prognostic factors in adult DTC patients with PM to help distinguish patients with different prognoses and inform the rational treatment regimens. Method: We performed a comprehensive search of the relevant studies published in the Cochrane Library, PubMed, Scopus, Embase, Wanfang database, VIP database, China National Knowledge Infrastructure, and Google Scholar from their inception until February 2021. The pooled hazard ratios (HR) for overall survival and/or progression-free survival (PFS) with 95% confidence intervals were applied to evaluate and identify the potential prognostic factors. Pooled OS at different time points were also calculated for the available data. A random-effects model was used in the meta-analysis. Results: The review and meta-analysis included 21 studies comprising 2722 DTC patients with PM. The prognostic factors for poor OS were: age over 40 years (HR=7.21, 95% confidence interval [CI] 1.52-34.10, P=0.01, N=788), age over 45 years (HR=2.18, 95% CI 1.26-3.77, P<0.01, N=601), male gender (HR=1.01, 95% CI 1.01-1.19, P=0.03, N=1396), follicular subtype of thyroid cancer (HR=1.63, 95% CI 1.36-1.96, P<0.01, N=2110), iodine non-avidity (HR=3.10, 95% CI 1.79-5.37, P<0.01, N=646), and metastases to other organs (HR=3.18, 95% CI 2.43-4.16, P<0.01, N=1713). Factors associated with poor PFS included age over 45 years (HR=3.85, 95% CI 1.29-11.47, P<0.01, N=306), male gender (HR=1.36, 95% CI 1.06-1.75, P=0.02, N=546), iodine non-avidity (HR=2.93, 95% CI 2.18-3.95, P<0.01, N=395), pulmonary metastatic nodule size over 10mm (HR=2.56, 95% CI 2.02-3.24, P<0.01, N=513), and extra-thyroidal invasion (HR=2.05, 95% CI 1.15-3.67, P=0.02, N=271). The pooled 1, 3, 5, 10, 15, and 20-years OS were 95.24%, 88.46%, 78.36%, 64.86%, 56.57%, and 51.03%, respectively. Conclusions: This review and meta-analysis identified the prognostic factors of DTC patients with PM. Notably, FTC, metastases to other organs, and iodine non-avidity were particularly associated with poor prognosis. The identified prognostic factors will help guide the clinical management of DTC patients with PM. Systematic review registration: https://inplasy.com/inplasy-2022-2-0026/, identifier (INPLASY202220026).

Competing risk model to determine the prognostic factors and treatment strategies for elderly patients with glioblastoma.

The prognostic factors and optimal treatment for the elderly patient with glioblastoma (GBM) were poorly understood. This study extracted 4975 elderly patients (≥ 65 years old) with histologically confirmed GBM from Surveillance, Epidemiology and End Results (SEER) database. Firstly, Cumulative incidence function and cox proportional model were utilized to illustrate the interference of non-GBM related mortality in our cohort. Then, the Fine-Gray competing risk model was applied to determine the prognostic factors for GBM related mortality. Age ≥ 75 years old, white race, size > 5.4 cm, frontal lobe tumor, and overlapping lesion were independently associated with more GBM related death, while Gross total resection (GTR) (HR 0.87, 95%CI 0.80-0.94, P = 0.010), radiotherapy (HR 0.64, 95%CI 0.55-0.74, P < 0.001), chemotherapy (HR 0.72, 95%CI 0.59-0.90, P = 0.003), and chemoRT (HR 0.43, 95%CI 0.38-0.48, P < 0.001) were identified as independently protective factors of GBM related death. Based on this, a corresponding nomogram was conducted to predict 3-, 6- and 12-month GBM related mortality, the C-index of which were 0.763, 0.718, and 0.694 respectively. The calibration curve showed that there was a good consistency between the predicted and the actual mortality probability. Concerning treatment options, GTR followed by chemoRT is suggested as optimal treatment. Radiotherapy and chemotherapy alone also provide moderate clinical benefits.

Fibroblasts play a potential role in bone destruction via osteopontin related caldesmon expression and polymerization in human non-functioning pituitary adenomas.

Non-functioning pituitary adenomas (NFPAs) are the most frequent pituitary tumors. The elucidation of the mechanisms of aggressive NFPAs in bone destruction is required in order to guide the clinical diagnosis and treatment of NFPAs. In the present study, we investigated the differential proteomics of fibroblasts isolated from clinical specimens of NFPAs with or without bone destruction. Proteomic analysis revealed a group of molecules associated with cytoskeleton organization, including caldesmon, were differentially expressed between fibroblasts isolated from bone destruction NFPAs (BD-NFPAs) and fibroblasts isolated from non-bone destruction NFPAs (NBD-NFPAs). The secreted proteins analysis found that osteopontin was significantly upregulated in BD-NFPAs fibroblasts. Furthermore, immunohistochemical staining of the NFPAs clinical samples showed that the expression of caldesmon in stromal cells and the expression of osteopontin in both tumor cells and stroma were significantly increased in BD-NFPAs. Taken together, our results indicate a possible way that osteopontin secreted from both NFPA cells and surrounding fibroblasts modify caldesmon expression and polymerization in fibroblasts, which may contribute to bone destruction in NFPA patients.

Langerhans cell histiocytosis of the thyroid complicated by papillary thyroid carcinoma: A case report and brief literature review.

RATIONALE: Langerhans cell histiocytosis (LCH) involves mainly the skin and bone and rarely the thyroid. Meanwhile, papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancer. Both LCH and PTC could make the thyroid enlarged and hypermetabolic. The coincidence of these 2 events in a patient is rare, and this paper aimed to report such case. PATIENT CONCERNS: A 40-year-old man presented with polyuria and polydipsia for 5 years. The symptoms had been relieved well by drug therapy for >4 years, until the drugs could not control the symptoms anymore and an extensively enlarged thyroid gland was noticed. DIAGNOSES: Thyroid ultrasound showed a nodule with microcalcification in the upper right lobe, positron emission tomography/computer tomography scan demonstrated thyroid hypermetabolism, and fine needle aspiration (FNA) revealed PTC. Right lobectomy of the thyroid and cervical lymph node biopsy verified the diagnosis "LCH of the thyroid complicated by PTC." INTERVENTIONS: The ultrasound-guided FNA biopsy was performed prior to right lobectomy of the thyroid and cervical lymph node biopsy. Postoperative histopathological examination confirmed the diagnosis, after which the patient received adjuvant chemotherapy. OUTCOMES: After 5 cycles of adjuvant chemotherapy, the patient had been followed up for 2 years. LCH was controlled satisfactorily and there was no significant sign of recurrence or metastasis of PTC. LESSONS: LCH of the thyroid complicated by PTC is rare. Thyroid involvement should always be considered in the differential diagnosis of LCH patients. Surgery for PTC followed by chemotherapy for LCH may be the suitable treatment.

Effect of dietary manganese on antioxidant status and expressions of heat shock proteins and factors in tissues of laying broiler breeders under normal and high environmental temperatures.

To investigate the effect of Mn on antioxidant status and on the expressions of heat shock proteins/factors in tissues of laying broiler breeders subjected to heat challenge, we used a completely randomised design (n 6) with a factorial arrangement of 2 environmental temperatures (normal, 21±1°C, and high, 32±1°C)×3 dietary Mn treatments (a Mn-unsupplemented basal diet (CON), or a basal diet supplemented with 120 mg Mn/kg diet, either as inorganic Mn sulphate (iMn) or as organic Mn proteinate (oMn)). There were no interactions (P>0·10) between environmental temperature and dietary Mn in any of the measured indices. High temperature decreased (P<0·003) Mn content, and also tended (P=0·07) to decrease Cu Zn superoxide dismutase (CuZnSOD) activity in the liver and heart. However, an increased Mn superoxide dismutase (MnSOD) activity (P<0·05) and a slight increase in malondialdehyde level (P=0·06) were detected in breast muscle. Up-regulated (P<0·05) expressions of heat shock factor 1 (HSF1) and HSF3 mRNA and heat shock protein 70 (HSP70) mRNA and protein were found in all three tissues. Broiler breeders fed either iMn or oMn had higher tissue Mn content (P<0·0001), heart MnSOD and CuZnSOD activities (P<0·01) and breast muscle MnSOD protein levels (P<0·05), and lower (P<0·05) breast muscle HSP70 mRNA and protein levels compared with those fed CON. Broiler breeders fed oMn had higher (P<0·03) bone Mn content than those fed iMn. These results indicate that high temperature decreases Mn retention and increases HSP70, HSF1 and HSF3 expressions in the tissues of laying broiler breeders. Furthermore, dietary supplementation with Mn in either source may enhance the heart's antioxidant ability and inhibit the expression of HSP70 in breast muscle. Finally, the organic Mn appears to be more available than inorganic Mn for bone in laying broiler breeders regardless of environmental temperatures.

Effect of dietary manganese on antioxidant status and expression levels of heat-shock proteins and factors in tissues of laying broiler breeders under normal and high environmental temperatures.

To investigate the effect of Mn on antioxidant status and expression levels of heat-shock proteins/factors in tissues of laying broiler breeders subjected to heat challenge, we used a completely randomised design (n 6) with a factorial arrangement of 2 environmental temperatures (normal, 21 (sem 1)°C and high, 32 (sem 1)°C)×3 dietary Mn treatments (an Mn-unsupplemented basal diet (CON), or a basal diet supplemented with 120 mg Mn/kg diet as inorganic Mn sulphate (iMn) or organic Mn proteinate (oMn)). There were no interactions (P>0·10) between environmental temperature and dietary Mn in all of the measured indices. High temperature decreased (P<0·003) Mn content, and also tended (P=0·07) to decrease copper zinc superoxide dismutase (CuZnSOD) activity in the liver and heart. However, an increased manganese superoxide dismutase (MnSOD) activity (P<0·05) and a slight increase of malondialdehyde level (P=0·06) were detected in breast muscle. Up-regulated (P<0·05) expression levels of heat-shock factor 1 (HSF1) and HSF3 mRNA and heat-shock protein 70 (HSP70) mRNA and protein were found in all three tissues. Broiler breeders fed either iMn or oMn had higher tissue Mn content (P<0·0001), heart MnSOD and CuZnSOD activities (P<0·01) and breast muscle MnSOD protein levels (P<0·05), and lower (P<0·05) breast muscle HSP70 mRNA and protein levels than those fed CON. Broiler breeders fed oMn had higher (P<0·03) bone Mn content than those fed iMn. These results indicate that high temperature decreases Mn retention and increases HSP70 and HSF1, HSF3 expression levels in tissues of laying broiler breeders. Furthermore, dietary supplementation with Mn in either source may enhance heart antioxidant ability and inhibit the expression of HSP70 in breast muscle. Finally, the organic Mn appears to be more available than inorganic Mn for bone in laying broiler breeders regardless of environmental temperatures.

Risk Factors for Nodal Metastasis in cN0 Papillary Thyroid Microcarcinoma.

BACKGROUND: Despite the majority of papillary thyroid microcarcinoma (PTMC) patients having an excellent prognosis, cervical lymph node metastases are common. The purpose of this study was to investigate the incidence and the predictive risk factors for occult central compartment lymph node metastasis (CLNM) in PTMC patients. MATERIALS AND METHODS: 178 patients with clinically node-negative (cN0) PTMC undergoing prophylactic central compartment neck dissection in our hospital from January 2008 to Jun 2010 were enrolled. The relationship between CLNM and the clinical and pathological factors such as gender, age, tumor size, tumor number, tumor location, extracapsular spread (ECS), and coexistance of chronic lymphocytic thyroiditis was analyzed. RESULTS: Occult CLNM was observed in 41% (73/178) of PTMC patients. Multivariate analysis showed that male gender, tumor size (≥6mm) and ECS were independent variables predictive of CLNM in PTMC patients. CONCLUSIONS: Male gender, tumor size (≥6mm) and ECS were risk factors of CLNM. We recommend a prophylactic central lymph node dissection (CLND) should be considered in PTMC patients with such risk factors.

[Study of interaction between levofloxacin and human serum albumin by multi-spectroscopic and molecular modeling methods].

Levofloxacin (LVFX) is widely used in clinical treatment due to it has a broad spectrum of in vitro activity against Gram-positive and Gram-negative bacteria. Human serum albumin (HSA) is the most abundant protein in plasma and constitutes approximately half of the protein founds in human blood. And more than 90% of the drugs used in people are bound to HSA. So it is commonly used for the investigation of drug-serum albumin interaction because the binding will significantly influence the absorption, distribution, metabolism excretion, stability and toxicity of the drugs. Therefore, detailed investigating the interaction of LVFX with HSA is very important to understand the pharmacokinetic behavior of the LVFX. In this paper, the interaction of LVFX and HSA has been studied fluorescence, UV, Fourier transform infrared (FT-IR) and molecular modeling method. The results indicated that LVFX induced the intrinsic fluorescence quenching of HSA though a static quenching procedure, and the effective binding constants (K(a)) were calculated to be 9.44 x 10(4) L x mol(-1) (294 K) and 2.74 x 10(4) L x mol(-1) (310 K) by used of the Stern-Volmer equation. According to the Vant's Hoff equation, the reaction was characterized by negative enthalpy (deltaH = -59.00 kJ x mol(-1)) and negative entropy (delta S = - 105.38 J x mol(-1) x K(-1)), indicated that the predominant forces in the LVFX-HSA complex were hydrogen bonding and van der Waals forces. By displacement measurements, the specific binding of LVFX in the vicinity of Site I of HSA was clarified. The binding distance of 3.66 nm between Trp214 and HSA was obtained by the Förster theory on resonance energy transfer. Furthermore, the binding details between LVFX and HSA were further confirmed by molecular docking studies, which were consistent with the experimental results. The alternations of protein secondary structure were calculated from FT-IR spectra. Upon formation of LVFX-HSA complexes, the amount of alpha-helical structures were decrease, but the numbers of beta-sheet structures, beta-turn structures and random structures were increase, respectively. This result indicated that LVFX induced unfolding of the polypeptides of HSA.

Overexpression of the human ubiquitin E3 ligase CUL4A alleviates hypoxia-reoxygenation injury in pheochromocytoma (PC12) cells.

The ubiquitin E3 ligase CUL4A plays important roles in diverse cellular processes including carcinogenesis and proliferation. It has been reported that the expression of CUL4A can be induced by hypoxic-ischemic injury. However, the effect of elevated expression of CUL4A on hypoxia-reoxygenation injury is currently unclear. In this study, human CUL4A (hCUL4A) was expressed in rat pheochromocytoma (PC12) cells using adenoviral vector-mediated gene transfer, and the effects of hCUL4A expression on hypoxia-reoxygenation injury were investigated. In PC12 cells subjected to hypoxia and reoxygenation, we found that hCUL4A suppresses apoptosis and DNA damage by regulating apoptosis-related proteins and cell cycle regulators (Bcl-2, caspase-3, p53 and p27); consequently, hCUL4A promotes cell survival. Taken together, our results reveal the beneficial effects of hCUL4A in PC12 cells upon hypoxia-reoxygenation injury.

Grade-specific expression profiles of miRNAs/mRNAs and docking study in human grade I-III astrocytomas.

Although several miRNAs have been identified to be involved in glioblastoma tumorigenesis, little is known about the global expression profiles of miRNAs and their functional targets in astrocytomas at earlier stages of malignancy. In this study the global expression of miRNAs and mRNAs in normal brain tissue samples and grade I-III astrocytomas were analyzed parallelly using microarrays, and the grade-specific expression profiles of them were obtained by unsupervised hierarchical clustering. It was also confirmed that miR-107, miR-124, miR-138, and miR-149 were downregulated significantly in grade I-IV astrocytomas, and overexpression of miR-124 and miR-149 inhibited glioblastoma cell proliferation and migration. Furthermore, grade-specific changes were discovered in the central biological processes, regulatory networks, and signaling pathways associated with dysregulated genes, and a regulatory network of putative functional miRNA-mRNA pairs was defined. In conclusion, our results may contribute to a better understanding of the molecular mechanisms involved in astrocytoma tumorigenesis and malignant progression.

[A pilot study on the impact of the drug resistance on the radioresistance in human pancreatic cancer cell lines].

OBJECTIVE: To investigate the impact of the drug resistance on the radioresistance in human pancreatic cancer cell lines. METHODS: Three drug resistant pancreatic cancer cell sublines induced by fluorouracil (5-FU), adriamycin (ADM) and gemcitabine respectively, SW1990/FU, SW1990/ADM and SW1990/Gz, were tested for the cell cycle and radio-sensitivity with flow cytometry and clonogenic assay. RESULTS: Compared with SW1990, the cell cycle assay indicated higher G(0)/G(1) period percentage in SW1990/FU and SW1990/Gz, but the G(2)/M period percentage decreased; SW1990/FU had the same while SW1990/Gz had lower S period percentage. SW1990/ADM almost had a similar cell cycle with SW1990. Clonogenic assay showed both SW1990/FU and SW1990/Gz had greater survival fraction (SF(2)) than SW1990, but SW1990/ADM had seemingly similar SF(2) as SW1990. CONCLUSION: Drug resistant pancreatic cancer cell lines have reduced G(2)/M period percentage and increased radioresistance.

[Establishment, characterization, and biological analysis of pancreatic adenocarcinoma cell strain SW1990/FU].

OBJECTIVE: To establish a 5-fluorouracil (5-FU)-resistant pancreatic adenocarcinoma (PAC) cell strain, and to investigate its biological characteristics. METHODS: The PAC cell strain SW1990 was selected into a multidrug-resistant cell strain stepwise with 5-FU, one of the most common drugs used in PAC chemotherapy, for 12 months and subsequently named SW1990/FU. The cell strain was characterized in terms of morphology, biology, and cross-resistance to adriamycin(ADM), mitomycin-C (MMC), and gemcitabine. BHLB/c-m nude mice tumor growth and CEA and CA19-9 levels were analyzed. In addition, karyotyping and FACS analysis were performed in SW1990/FU and SW1990. RESULTS: The SW1990/FU cell strain was 132.7 times more resistant to 5-FU than the parental SW1990 cells, and exhibited cross-resistance to other agents. Compared to the parental cells, SW1990/FU cells exhibited a smaller growth rate, delayed cell-doubling time, and specific changes in chromosomes 18. Tumor diameters in multidrug resistance and parental cells inoculated in in vivo experiments were (1.5 +/- 0.30) cm and (0.8 +/- 0.15) cm, respectively. CONCLUSIONS: Morphological adaptation and intracellular changes can be induced by drug challenge in PAC cells. SW1990/FU may be used as an experimental system for the search to overcome drug resistance and to elucidate possible mechanisms of acquired drug resistance in human pancreatic cancer.

Detection of multidrug resistant gene 1 in pancreatic cancer.

BACKGROUND: The results are conflicting in detecting P-glycoprotein (P-gp) in pancreatic cancer. The aim of this study was to detect the expression of multidrug resistant gene 1 (MDR1) in pancreatic cancer cell lines. METHODS: MDR1 mRNA and P-gp were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical assay (IHC) in three pancreatic cancer cell lines SW1990, CAPAN-1 and P3. P-gp functions were evaluated through the rhodamine extrusion test. RESULTS: Two of the three cell lines expressed MDR1 positively at different levels. The rhodamine extrusion test showed that the percentage of positive cells in MDR(+) cells was significantly lower than that in MDR1(-) cells. The results of IHC, RT-PCR and the rhodamine extrusion test were consistent with each other. CONCLUSION: All of these methods are reliable in the detection of MDR1 in pancreatic cancer tissue, thus providing a guide for clinical chemotherapy of pancreatic cancer.

[Assessment of unresectability of pancreatic carcinoma by enhanced-CT and selective angiography].

BACKGROUND & OBJECTIVE: One of the major limitations of curative resection in the patients with pancreatic cancer is local tumor extension to the major vessels surrounding pancreas. Therefore the assessment of the involvement of major arteries surrounding pancreas by tumor before operation is very important for the judgement of respectability of pancreatic carcinoma. This study was designed to assess the clinical value of contrast-enhanced CT(CECT) and selective angiography (SAG) in predicting the unresectability of patients with pancreatic cancer. METHODS: From Aug 7, 1996 to Aug 12, 2000, 67 patients with pancreatic ductal adenocarcinoma proved pathologically were retrospectively analyzed. Of these patients, 31 and 54 patients were treated with CECT and SAG, respectively. The involvement of major vessels surrounding pancreas in CECT and SAG were assessed by operator according to specific criterias, which were compared with finding in operation. Finally, the accuracy of the method was assessed. RESULT: Among 31 cases who were treated with CECT, 13 were judged unresectable by CECT; and 12 were found unresectable during operation, with predict value of 91%. Among 54 cases who were treated with SAG, 28 were judged unresectable by SAG; and 23 were found unresectable during operation, with predict value of 82%. The sensitivity, specificity, and predict value of CECT and SAG were 60%, 91%, 92%, and 77%, 79%, 82%, respectively. The sensitivity, specificity, and predict value of CECT combined with SAG were 91%, 100%, 100%, respectively. CONCLUSION: Enhanced CT and SAG are useful in assessing the unresectability of pancreatic carcinoma, the combination of two ways can improve the sensitivity, specificity and predict value.