Human Gallbladder Research Articles

Hydroxytyrosol inhibits cholangiocarcinoma tumor growth: An in vivo and in vitro study

Cholangiocarcinoma (CCA) is a type of digestive tumor that is associated with a high rate of mortality due to the difficulty of early diagnosis and the resistance of this tumor type to chemotherapy. Hydroxytyrosol (HT), which is derived from virgin olive oil (VOO), has recently been reported to inhibit the proliferation of various types of human cancer cells. In the present study, we investigated the effect of HT on CCA. The antiproliferative and proapoptotic effects of HT on CCA were evaluated in the human CCA cell lines TFK-1 and KMBC and the human gallbladder cancer cell line GBS-SD. We also assessed this effect in vivo. We found that 75 µM HT inhibited the proliferation of the TFK-1, KMBC and GBS-SD cell lines. However, 200 µM HT treatment did not affect the proliferation of the human bile duct cell line HIBEpiC. More importantly, HT (250 and 500 mg/kg/day) markedly inhibited the growth of CCA xenografts in mice. G2/M phase cell cycle arrest and apoptosis were observed using flow cytometry and western blotting, and we also noted a time- and dose-dependent inhibition of phospho-ERK, with no changes in total-ERK, during treatment with HT. The present study showed that HT induces cell cycle arrest and apoptosis in vitro and in vivo. These data suggest that HT, which possesses excellent biocompatibility and few side-effects, could be developed as a novel agent against CCA.

The expression of deleted in malignant brain tumors 1 gene in gallbladder carcinoma and its clinical significance

Objective To observe the expression of deleted in malignant brain tumors 1 (DMBT1) gene in human gallbladder carcinoma.Methods The samples were obtained from 12 cases with gallbladder carcinoma specimens.Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) strategies and Western blotting were used for analyzing the DMBT1 mRNA and protein expression in 12 samples and adjacent noncanerous tissues.Results DMBT1 mRNA and protein expression were not detected in 91.7％ of human gallbladder carcinoma and in of 16.7％ adjacent noncanerous tissues (P ＜0.05).Conclusion DMBT1 activation might be in human gallbladder carcinoma.DMBT1 gene may play some roles in the pathogenesis of human gallbladder carcinoma. Key words: Gallbladder carcinoma; Deleted in malignant brain tumors 1 gene

Role of Aquaporin-5 in Gallbladder Carcinoma

Background/Purpose: Aquaporins (AQPs) are important in controlling bile formation. However, the exact role in human gallbladder carcinogenesis has not yet been defined. Methods: AQP-5-expressing gallbladder carcinoma (GBC) cell lines (NOZ) were transfected with anti-AQP-5 small interfering RNA (siRNA). Growth, migration, invasion assay, and drug susceptibility tests were performed. Next, microRNA (miRNA) expression was analyzed by miRNA oligo chip (3D-Gene®). AQP-5 and AQP-5-related miRNA target gene expressions were also analyzed using tissue microarray (TMA) in 44 GBC samples. Results: Treatment with AQP-5 siRNA decreased cell proliferation, migration, and invasion. On the other hand, those cells increased IC₅₀ of gemcitabine. By performing miRNA assays, miR-29b, -200a, and -21 were shown to be highly overexpressed in cells treated with AQP-5 siRNA NOZ. When focusing on miR-21, phosphatase and tensin homolog (PTEN) was found to be a target of miR-21. In the TMA, AQP-5/PTEN coexpression was significantly associated with the depth of invasion and MIB-1 index (p = 0.003, 0.010). Survival of patients with a high AQP-5/PTEN coexpression was longer than that of patients with a low coexpression (p = 0.003). Conclusions: Our result suggested that miR-21 and PTEN may contribute to the role of AQP-5 in GBC. AQP-5 and PTEN cascades are favorable biomarkers of GBC.

Human gall-bladder communicating with skin: rare anatomical swerve.

Cholecysto-cutaneous fistula is an extremely rare phenomenon in present era. We report a case of this rare entity wherein patient presented with unique history of passage of stones per umbilicus. Newer radiological investigations specifically CT fistulography help in surgical planning by not only delineating external fistulas but only diagnosing any internal fistula.

Histological study of human gallbladder

Background & objectives: Gallbladder is one of the organs having a wide spectrum of diseases ranging from congenital anomalies, calculi and its complications, non-inflammatory, inflammatory to the neoplastic lesions. Gallstones are one of the major causes of morbidity and mortality all over the world affecting 10% of adult population. While Gallbladder cancer is a disease of the elderly; it affects patients in their 70s, with a female to male ratio 5:1. The aim was to study the distribution with respect to age and sex and the usefulness of histological evaluation of gallbladder. Methods: This is a retrospective study of 100 cases of gallbladder lesions during the period of April 2010 to October 2011. Results: Lesions of gallbladder were more common seen in females with a male to female ratio of 1:2.3. Gallbladder lesions were more commonly found in 4th & 5th decades of the patients. Out of 100 cases, Non- neoplastic lesions found in 95 cases (95%) and Neoplastic lesion found in 5 cases (5%) with the ratio being 19:1. The commonest histological observation found was chronic calculous cholecystitis in 46 cases (46%) followed by acute calculous cholecystitis in 9 cases (9%). Conclusion: Female in their 4th decade are common sufferer of Gallbladder diseases. Gallstones and their consequences are the major factors for histomorphological changes of cholecystitis. Histological examination help where adjuvent treatment is depend up on grade, severity & Extent of invasion and also to rule out suspicion about malignancy.

AKT/mTOR substrate P70S6K is frequently phosphorylated in gallbladder cancer tissue and cell lines

BackgroundGallbladder carcinoma is a highly malignant tumor and a public health problem in some parts of the world. It is characterized by a poor prognosis and its resistance to radio and chemotherapy. There is an urgent need to develop novel therapeutic alternatives for the treatment of gallbladder carcinoma. The mammalian target of the rapamycin (mTOR) signaling pathway is activated in about 50% of human malignancies, and its role in gallbladder carcinoma has previously been suggested. In the present study, we investigated the phosphorylation status of the mTOR substrate p70S6K in preneoplastic and neoplastic gallbladder tissues and evaluated the effect of three mTOR inhibitors on cell growth and migration in gallbladder carcinoma cell lines.MethodsImmunohistochemical staining of phospho-p70S6K was analyzed in 181 gallbladder carcinoma cases, classified according to lesion type as dysplasia, early carcinoma, or advanced carcinoma. Protein expression of AKT/mTOR members was also evaluated in eight gallbladder carcinoma cell lines by Western blot analysis. We selected two gallbladder carcinoma cell lines (G415 and TGBC-2TKB) to evaluate the effect of rapamycin, RAD001, and AZD8055 on cell viability, cell migration, and protein expression.ResultsOur results showed that phospho-p70S6K is highly expressed in dysplasia (66.7%, 12/18), early cancer (84.6%, 22/26), and advanced cancer (88.3%, 121/137). No statistical correlation was observed between phospho-p70S6K status and any clinical or pathological features, including age, gender, ethnicity, wall infiltration level, or histological differentiation (P < 0.05). In vitro treatment with rapamycin, RAD001, and AZD8055 reduced cell growth, cell migration, and phospho-p70S6K expression significantly in G-415 and TGBC-2TKB cancer cells (P < 0.001).ConclusionOur findings confirm the upregulation of this signaling pathway in gallbladder carcinoma and provide a rationale for the potential use of mTOR inhibitors as a therapeutic strategy for human gallbladder carcinoma.

Clinicopathological significance of SLP-2 overexpression in human gallbladder cancer

Several studies have indicated that overexpression of stomatin-like protein 2 (SLP-2) has been identified in several types of cancer. However, its role and clinical relevance in gallbladder cancer (GBC) is unknown. The purpose of this study was to reveal the prognostic significance of SLP-2 in GBC. The SLP-2 expression was examined at mRNA and protein levels by real-time quantitative polymerase chain reaction (qRT-PCR), and immunohistochemistry in GBC tissues and adjacent noncancerous tissues. Statistical analyses were applied to test the associations between SLP-2 expression, clinicopathologic factors, and prognosis. Immunohistochemistry and qRT-PCR showed that the protein and mRNA expression levels of SLP-2 were both significantly higher in GBC tissues than in adjacent noncancerous tissues. In addition, immunohistochemistry analysis showed that SLP-2 expression was significantly correlated with histological grade (P <0.001), pathologic T stage (P = 0.019), clinical stage (P = 0.001), and lymph node metastasis (P = 0.026). The Kaplan-Meier survival curves indicated that patients with high expression of SLP-2 had shorter overall survival than those with low expression (P <0.001). Meanwhile, the Cox multivariate analysis indicated that high expressions of SLP-2 were an independent prognostic factor for patients with GBC. These data showed that SLP-2 may play an important role in human GBC tumorigenesis, and SLP-2 might serve as a novel prognostic marker in human GBC.

The role of the gallbladder in humans

The basic function of the gallbladder in humans is one of protection. The accumulation of the primary bile acids (cholic acid and chenodeoxycholic acid) in the gallbladder reduces the formation of the secondary bile acids (deoxycholic acid and lithocholic acid), thus diminishing their concentration in the so-called gallbladder-independent enterohepatic circulation and protecting the liver, the stomach mucosa, the gallbladder, and the colon from their toxic hydrophobic effects. The presence or absence of the gallbladder in mammals is a determining factor in the synthesis of hydrophobic or hydrophilic bile acids. Because the gallbladder contracts 5-20 min after food is in the stomach and the "gastric chyme" moves from the stomach to the duodenum 1-3 h later, the function of the gallbladder bile in digestion may be insignificant. The aim of this article was to provide a detailed review of the role of the gallbladder and the mechanisms related to bile formation in humans.

Bcl-2 gene silencing by RNA interference inhibits the growth of the human gallbladder carcinoma cell line GBC-SD in vitro and in vivo

Gallbladder carcinoma is the most common malignant tumor in the biliary system; however, the underlying mechanisms of tumor initiation, progression and metastasis are not fully understood to date. The B-cell lymphoma/leukemia-2 (Bcl-2) gene, which is highly expressed in gallbladder carcinoma tissue, is one of the most important regulatory factors in cell apoptosis, and plays an important role in the initiation and progression of gallbladder carcinoma. In the present study, we constructed a eukaryotic expression vector of small interference RNA (siRNA) specific to the Bcl-2 gene and transfected it into GBC-SD human gallbladder carcinoma cells. We demonstrated that the constructed Bcl-2 siRNA vector effectively silenced Bcl-2 gene expression in the GBC-SD human gallbladder carcinoma cells, inhibited cell proliferation, induced cell apoptosis, increased chemotherapeutic sensitivity to 5-fluorouracil and inhibited tumor growth invivo. Collectively, these data reveal an important contribution of Bcl-2 to gallbladder carcinoma. Thus, the use of a synthetic inhibitor of Bcl-2 may be a promising approach for the treatment of gallbladder carcinoma.

Anti-proliferation effect of curcumin on human gallbladder carcinoma cell line

Objective To explore the anti-proliferation effect of curcumin on human gallbladder carcinoma GBC-SD cells and its mechanism.Methods The growth inhibition of GBC-SD cells treated with curcumin of 0,10,30,50,and 70 mg/L was detected by using methyl thiazol tetrazolium (MTT) assay.The growth inhibition of GBC-SD cells treated with curcumin of 30 mg/L at 0,12,24,48 and 72 h was detected.Control group,10 mg/L curcumin group,30 mg/L curcumin group and 50 mg/L curcumin group were set up.The apoptosis rate was tested by using flow cytometry.After curcumin treatment for 24 h,the expression levels of nuclear factor-κB (NF-κB) and Cyclin D1 were detected by using Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR),respectively.The mRNA levels of bax and B lymphocytes/leukemia-2 (bcl-2) were examined by using real-time reverse transcription polymerase chain reaction.Results Curcumin could significantly inhibit the viability of GBC-SD cells in a time-and dosedependent manner.After treatment with curcumin (10,30,and 50 mg/L),the survival rate was (95.34 ±9.21)％,(70.63 ± 11.09)％ and (50.58 ± 6.31)％,respectively.There was significant difference between control group and 30 mg/L curcumin group or 50 mg/L curcumin group (P ＜ 0.05) ;The apoptosis rate was (9.83 ± 1.98)％,(37.25 ± 1.21)％ and (57.63 ±7.38)％,respectively.There was significant difference between control group and 30 mg/L curcumin group or 50 mg/L curcumin group (P ＜ 0.05).30 mg/L and 50 mg/L curcumin could down-regulate the expression of NF-κB and CyclinD1,reduce the expression of bcl-2 and enhance the expression of bax.However,10 mg/L curcumin had no evident effect on genes mentioned above.Conclusion Curcumin could not only down-regulate the expression of NF-κB and Cyclin D1,but also reduce the mRNA level of bcl-2 and up-regulate the mRNA level of bax,causing the reduced bcl-2/bax ratio,which could effectively inhibit the proliferation of gallbladder carcinoma GBC-SD cells and induce cell apoptosis. Key words: Curcumin; Gallbladder carcinoma; Apoptosis

Inhibition of SCAMP1 suppresses cell migration and invasion in human pancreatic and gallbladder cancer cells

Lymph node (LN) metastasis is one of the most important risk factors for the prognosis of pancreatic cancer. This study aimed to identify novel LN metastasis-associated markers and therapeutic targets for pancreatic and gallbladder cancers. DNA microarray analysis was carried out to identify genes differentially expressed between 17 pancreatic cancer tissues with LN metastasis and 17 pancreatic cancer tissues without LN metastasis. The expression of LZIC, FXR, SCAMP1, and SULT1E1 is significantly higher in pancreatic cancer tissues with LN metastasis than in pancreatic cancer tissues without LN metastasis. We recently reported that FXR plays an important role in LN metastasis of pancreatic cancer, and in this study, we selected the secretory carrier membrane protein 1 (SCAMP1) gene. To determine that function of the SCAMP1 gene, we examined the effects of SCAMP1 knockdown on pancreatic and gallbladder cancer proliferation, migration, and invasion using SCAMP1 small interfering RNA (siRNA) and the activity of vascular endothelial growth factor (VEGF) was measured by enzyme-linked immunosorbent assay. SCAMP1 overexpression is associated with LN metastasis in pancreatic cancer patients. The siRNA-mediated downregulation of SCAMP1 resulted in a marked reduction in cell migration and invasion, but not proliferation in MIA-PaCa2, PANC-1, TGBC-1, and TGBC-2 cells. In addition, downregulation of SCAMP1 inhibited VEGF levels of conditioned medium from SCAMP1 siRNA-transfected cells. These results suggest that downregulation of SCAMP1 could be a potential therapeutic target for patients with pancreatic and gallbladder cancer.

Mo2100 Pituitary Adenylate Cyclase Activating Peptide (PACAP) Causes Human Gallbladder Relaxation Through VPAC1 and VPAC2 Receptors

Mo2100 Pituitary Adenylate Cyclase Activating Peptide (PACAP) Causes Human Gallbladder Relaxation Through VPAC1 and VPAC2 Receptors

Mo1778 Regulation of MicroRNAs by p53 in Functional Tumor-Initiating Cells of Human Gallbladder Cancer

Mo1778 Regulation of MicroRNAs by p53 in Functional Tumor-Initiating Cells of Human Gallbladder Cancer

Expression of N-acetylglucosaminyltransferase V in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder

N-Acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the β1-6 branching of N-acetylglucosamine on asparagine-linked oligosaccharides of cellular proteins, enhances the malignant behaviors of carcinoma cells in experimental models. The aim of this study was to determine clinical significance of GnT-V expression in human pT2 gallbladder carcinoma with simple in vitro experiments. Ninety patients with pT2 gallbladder carcinoma were included for this study. The in vitro and in vivo biological effects of GnT-V were investigated using gallbladder carcinoma cells with variable GnT-V expression levels induced by a small interfering RNA. Of the 90 cases, 57 showed positive staining and the remaining 33 demonstrated negative staining, the subcellular localization in the 57 cases was classified into the granular-type in 31 cases and the diffuse-type in 26 cases. In 76 cases with curative resection, postsurgical survival was significantly poorer in those showing positive staining than in those showing negative staining (P=0.028). In all of the 76 cases, postsurgical recurrence was significantly more frequent in those showing diffuse-type localization than in those showing negative staining. Experimental analyses demonstrated that the down-regulation of GnT-V expression in gallbladder carcinoma cells induced suppression of cell growth in vitro. The expression levels of GnT-V in the cells were highly correlated with the rapid in vivo growth coupled with the enhanced angiogenesis, and the tendency to form liver metastasis. GnT-V expression in the subserosal layer of pT2 gallbladder carcinoma is correlated with the aggressiveness of the disease.

Abstract 2575: Differential anti-tumor activities of curcumin against apoptosis and cell Cycle progression in Src- and Ras-activated human gallbladder carcinoma cells.

Abstract Curcumin, a phytochemical in turmeric, has been studied as a potential anticancer drug targeting multiple signaling molecules. However, the role of Src and Ras signaling pathways in curcumin sensitivity remains unknown. We investigated therefore the molecular mechanism of anti-proliferative and apoptosis-inducing activities of curcumin in HAG-1 human gallbladder adenocarcinoma cells transfected with either activated Src (HAG/src3-1) or Ras (HAG/ras5-1). Effects of curcumin on proliferation, apoptosis, cell cycle perturbation, and signal proteins for survival, proliferation, and apoptosis were evaluated by WST-1 assay, FACS analyses and Western blotting. Activation of either Src or Ras did not confer resistance to curcumin compared to HAG/neo3-5 vehicle-transfected cells, producing similar IC50 concentrations of curcumin among these 3 cell lines. Upon treatment with curcumin, constitutive activities of Erk1/2 were enhanced, but those of Akt were significantly inhibited in these three cell lines, with subsequent reductions of activities of downstream mTOR and S6K1. The sub-G0/G1 apoptotic cell populations were substantially increased in all cell lines with demonstrable cleavage of PARP, but this increase was most prominent in Src-activated cells. Reduced expression and phosphorylation of Bcl-2 and enhanced expression of Bax were demonstrated to have a causative role for the curcumin-induced apoptosis in Src-driven, but not Ras-driven cells. By contrast, drastic increases of the proportion of cells in a G2/M phase were seen in Ras-activated cells, suggesting a potential role of Ras/Erk1/2 activation in curcumin-induced G2/M cell cycle arrest. These data indicate that curcumin-induced growth declines would be mediated mainly by G2/M arrest of the cell cycle in Ras-driven cells but by apoptosis induction in Src-driven cells. Taken together, the results indicate that curcumin exhibits differential activities against apoptosis and cell cycle progression, depending on activation mechanisms of signal transduction, and that curcumin can overcome Src- and Ras-driven activation of downstream signaling pathways, thus providing evidence of potential application of curcumin for the treatment of human cancers with activated Src or Ras. Citation Format: Misaki Ono, Takako Higuchi, Mikako Takeshima, Chen Chen, Shuji Nakano. Differential anti-tumor activities of curcumin against apoptosis and cell Cycle progression in Src- and Ras-activated human gallbladder carcinoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2575. doi:10.1158/1538-7445.AM2013-2575

Contribution of the PI3K/MMPs/Ln-5γ2 and EphA2/FAK/Paxillin signaling pathways to tumor growth and vasculogenic mimicry of gallbladder carcinomas

Vasculogenic mimicry (VM) is a new tumor blood supply in some highly aggressive malignant tumors. We previously reported VM in human gallbladder carcinomas, 3-D matrices in vitro and nude mouse xenografts in vivo of highly aggressive GBC-SD cells and its clinical significance. In this study, we further studied the underlying mechanisms of VM in gallbladder carcinomas via the 3-D matrix in vitro, the nude mouse xenografts in vivo of GBC-SD or SGC-996 cells, immunohistochemistry (H&E staining and CD31-PAS double staining), electron microscopy, expression of MMP-2, MT1-MMP, PI3K, Ln-5γ2, EphA2, FAK and Paxillin-P proteins/mRNAs determined by SABC, ELISA, immunofluorescence, western blotting and qRT-PCR, respectively. It was shown that all of untreated highly aggressive GBC-SD cells and xenografts formed vasculogenic-like structures within 2 weeks of seeding and injecting, and facilitated the growth of tumor cells or xenografts; whereas poorly aggressive SGC-996 cells or GBC-SD cells treated by TIMP-2 were unable to form the vasculogenic-like structures with the same conditions; and tumor xenograft growth was inhibited. Expression of MMP-2, MT1-MMP proteins/mRNAs from sections and supernates of 3-D matrix in vitro, expression of PI3K, MMP-2, MT1-MMP, Ln-5γ2, EphA2, FAK and Paxillin-P proteins/mRNAs from sections of xenografts in vivo in untreated GBC-SD group was upregulated significantly (all P<0.001); however, expression of these VM signal-related proteins/mRNAs in the SGC-996 group and GBC-SD treated by the TIMP-2 group was significantly downregulated (all P<0.001). Thus, we identified for the first time that highly aggressive GBC-SD cells formed VM in vitro and in vivo through the upregulation of PI3K/MMPs/Ln-5γ2 and/or EphA2/FAK/Paxillin signaling. PI3K/MMPs/Ln-5γ2 and EphA2/FAK/Paxillin as key signaling pathways in a coordinated manner contributed to tumor growth and VM of gallbladder carcinomas and provided novel targets that could be potentially exploited for therapeutic intervention of human gallbladder carcinomas.

Anisotropic behaviour of human gallbladder walls

Inverse estimation of biomechanical parameters of soft tissues from non-invasive measurements has clinical significance in patient-specific modelling and disease diagnosis. In this paper, we propose a fully nonlinear approach to estimate the mechanical properties of the human gallbladder wall muscles from in vivo ultrasound images. The iteration method consists of a forward approach, in which the constitutive equation is based on a modified Hozapfel–Gasser–Ogden law initially developed for arteries. Five constitutive parameters describing the two orthogonal families of fibres and the matrix material are determined by comparing the computed displacements with medical images. The optimisation process is carried out using the MATLAB toolbox, a Python code, and the ABAQUS solver. The proposed method is validated with published artery data and subsequently applied to ten human gallbladder samples. Results show that the human gallbladder wall is anisotropic during the passive refilling phase, and that the peak stress is 1.6 times greater than that calculated using linear mechanics. This discrepancy arises because the wall thickness reduces by 1.6 times during the deformation, which is not predicted by conventional linear elasticity. If the change of wall thickness is accounted for, then the linear model can used to predict the gallbladder stress and its correlation with pain. This work provides further understanding of the nonlinear characteristics of human gallbladder.

The Genomic Blueprint of Salmonella enterica subspecies enterica serovar Typhi P-stx-12

Salmonella enterica subspecies enterica serovar Typhi is a rod-shaped, Gram-negative, facultatively anaerobic bacterium. It belongs to the family Enterobacteriaceae in the class Gammaproteobacteria, and has the capability of residing in the human gallbladder by forming a biofilm and hence causing the person to become a typhoid carrier. Here we present the complete genome of Salmonella enterica subspecies enterica serotype Typhi strain P-stx-12, which was isolated from a chronic carrier in Varanasi, India. The complete genome comprises a 4,768,352 bp chromosome with a total of 98 RNA genes, 4,691 protein-coding genes and a 181,431 bp plasmid. Genome analysis revealed that the organism is closely related to Salmonella enterica serovar Typhi strain Ty2 and Salmonella enterica serovar Typhi strain CT18, although their genome structure is slightly different.

Expression of carboxyl terminus of Hsp70-interacting protein (CHIP) indicates poor prognosis in human gallbladder carcinoma

Gallbladder carcinoma (GBC) is a lethal neoplasm, and new prognostic markers are required. Deregulation of E3 ligases contributes to cancer development and is associated with poor prognosis. Carboxyl terminus of heat shock protein 70-interacting protein (CHIP) is a U-box-type E3 ubiquitin ligase, the role of which has not been evaluated in GBC. Therefore, the present study investigated CHIP expression in GBC and its prognostic significance. In the present study, CHIP expression was measured in 78 tumor specimens of GBC by immunohistochemistry and the correlation between CHIP expression and clinicopathological factors was analyzed. Of the tumor specimens, 26.9% showed high staining intensity [the CHIP high expression group (HEG)]. The CHIP-HEG was not associated with other common clinicopathological parameters, including T stage, and lymph node and distant metastases. CHIP-HEG patients had a significantly worse prognosis than patients with low CHIP expression with median cancer-specific survival times of 8.0 months (range, 1–34 months) and 13.0 months (range, 1–110 months), respectively (P=0.023). Multivariate analyses showed that CHIP expression was close to being an independent risk factor for predicting patient survival. CHIP expression may be associated with a poor prognosis in GBC. Since CHIP is not associated with other clinicopathological prognostic factors, it may serve as an ideal molecular marker for predicting patient outcomes.

Histological Changes in Human Gallbladder in Pathological Condition Including Cholecystitis and Cholelithiasis an Analytical Study

Histological Changes in Human Gallbladder in Pathological Condition Including Cholecystitis and Cholelithiasis an Analytical Study