Biological Behavior Of Tumor Research Articles

The role of Transfer RNA-Derived Small RNAs (tsRNAs) in Digestive System Tumors.

Transfer RNA-derived small RNA(tsRNA) is a type of non-coding tRNA undergoing cleavage by specific nucleases such as Dicer. TsRNAs comprise of tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs). Based on the splicing site within the tRNA, tRFs can be classified into tRF-1, tRF-2, tRF-3, tRF-5, and i-tRF. TiRNAs can be classified into 5′-tiRNA and 3′-tiRNA. Both tRFs and tiRNAs have important roles in carcinogenesis, especially cancer of digestive system. TRFs and tiRNAs can promote cell proliferation and cell cycle progression by regulating the expression of oncogenes, combining with RNA binding proteins such as Y-box binding protein 1 (YBX1) to prevent transcription. Despite many reviews on the basic biological function of tRFs and tiRNAs, few have described their correlation with tumors especially gastrointestinal tumor. This review focused on the relationship of tRFs and tiRNAs with the biological behavior, clinicopathological characteristics, diagnosis, treatment and prognosis of digestive system tumors, and would provide novel insights for the early detection and treatment of digestive system tumors.

Breast cancer animal models and applications.

Breast cancer is the most common malignancy in women. Basic and translational breast cancer research relies heavily on experimental animal models. Ideally, such models for breast cancer should have commonality with human breast cancer in terms of tumor etiology, biological behavior, pathology, and response to therapeutics. This review introduces current progress in different breast cancer experimental animal models and analyzes their characteristics, advantages, disadvantages, and potential applications. Finally, we propose future research directions for breast cancer animal models.

A Study on the Expression of SPRED1 and PBRM1 (Baf180) and their Clinical Significances in Patients with Gastric Cancer.

To evaluate SPRED1 and PBRMl expression in patients with gastric cancer and determine the biological relationships of SPRED1 and PBRM1 with the occurrence and development of gastric cancer. Tissue specimens of patients with gastric cancer at Jingzhou First People's Hospital were gathered from April 2016 to August 2018. SPRED1 and PBRMl (Baf180) protein expression levels were detected in the excised cancerous tissues and normal tissues (control group) of 80 patients with gastric cancer by immunohistochemical methods. The positive rates of SPRED1 and PBRMl protein expression in gastric cancer tissues were 55% and 75%, respectively. The positive rates of SPRED1 and PBRMl protein expression in the normal tissues without cancer were 84.6% and 92.3%, respectively. The expression in gastric cancer tissues was significantly lower than that of the control group (p < 0.05). Positive SPRED1 and PBRMl protein expression was related to histological type, depth of infiltration, presence of lymphatic metastasis, pathological grade, and clinical TNM phase (p < 0.05). SPRED1 expression and PBRMl expression were positively correlated. The expression of SPRED1 and PBRMl in gastric cancer tissues is low, unrelated to age and declines with increasing pathological grade and clinical phase of the gastric cancer tissues. SPRED1 and PBRMl expression may be related to the biological behavior of tumors, and the two may have a synergistic effect.

Main pancreatic duct to parenchymal thickness ratio and degree of atrophy are associated with overall survival in primarily resected pancreatic cancer

Background: Ductal adenocarcinoma of the pancreatic head induces morphological changes of the gland structure, with potential parenchymal degeneration and main pancreatic duct (MPD) dilation. Aim of this study was to evaluate whether these radiologic findings are associated with oncologic outcomes. Material & Methods: From an institutional prospectively maintained database, patients who underwent upfront pancreatoduodenectomy and had a preoperative CT-scan imaging available were assessed. Included patients were divided into short- (3-12 months following surgery) and long-term (≥36 months) survivors. Thickness of the pancreatic gland, parenchymal atrophy, size of the MPD, and distance of the tumor from the ampulla were assessed at the preoperative CT-scan. Results: One-hundred-eighteen patients were included, 68 (57.6%) in the short- and 50 (42.4%) in the long-term survival group. Patients in the short-term survival group had significantly higher Ca19-9 levels (p=0.027), larger tumors (32.6±12.1mm vs. 26.5±11.6mm, p=0.008), poorer differentiation (p=0.003), higher positive R-status rate (p=0.008), and reduced receipt of adjuvant chemotherapy (p=0.020). A significant difference in parenchymal atrophy between groups was also detected (p=0.032). Moreover, the MPD-to-pancreatic thickness ratio normalized for the distance from the ampulla was significantly lower in the short-term group (3.6±6.2 vs. 8.2±12.0mm, p=0.016). At survival analysis, the MPD-to-pancreatic thickness ratio and the degree of parenchymal atrophy were associated with OS (p=0.01 and p=0.020, respectively; log-rank test). At a multivariate Cox-proportional hazards regression model, only the MPD-to-pancreatic thickness ratio, dichotomized at the best predictive value, was independently associated with OS (HR=0.48; p=0.015), together with positive R-status (HR=1.78; p=0.040), and receipt of adjuvant treatment (HR=0.48; p=0.015). Conclusions: A high MPD-to-pancreatic thickness ratio normalized for the distance from the ampulla predicts improved long-term survival in patients undergoing upfront resection for cancer of the pancreatic head. Whether these radiologic features are related to different biological tumor behavior remains elusive and should be addressed in further studies.

Diagnostic, clinicopathologic, therapeutic and prognostic value of Plasma Heat Shock Protein 90 levels in patients with advanced Gastrointestinal Carcinoma.

Purpose: Heat shock protein 90 (HSP90) is a critical molecular chaperone for protein folding, intracellular disposition and regulation of tumor biological behavior in the extracellular space. HSP90 has received much attention due to its specific effect in gastrointestinal cancer. This clinical study sought to determine whether HSP90 in plasma may serve as a biomarker in patients with advanced gastrointestinal carcinoma.Methods: Using human plasma samples of advanced gastrointestinal carcinoma, we investigated the specific value of HSP90 in gastrointestinal cancer from a clinical perspective.Results: In summary, plasma levels of HSP90 were shown to be higher in patients with gastric cancer (GC) or colorectal cancer (CRC) than in controls with benign gastrointestinal diseases. In both GC and CRC patients, HSP90 was significantly associated with live metastasis. Higher HSP90 levels were more frequent in CRC patients with hazardous or harmful alcohol consumption habits. Patients with RAS mutations had higher HSP90 levels in CRC. Compared with Carcinoembryonic Antigen (CEA) and Carbohydrate Antigen 19-9 (CA19-9), HSP90 benefited patients by enhancing diagnostic sensitivity and the Youden index. The levels of HSP90 were inversely associated with short-term efficacy in GC patients who had received fluorouracil/platinum-based advanced first-line treatment. When first-line therapy failed, plasma HSP90 levels in patients with GC were significantly increased. In terms of progression-free survival (PFS), patients with GC or CRC who had low levels of HSP90 were not significantly different from those with high levels of HSP90. Univariate and multivariate analyses demonstrated that HSP90 was not an independent prognostic predictor for GC and CRC patients with PFS. However, RAS mutation was an independent prognostic factor for poor PFS in CRC patients.Conclusions: Plasma HSP90 levels have potential diagnostic value in advanced gastrointestinal carcinoma and therapeutic predictive value in GC.

A Review on the Update of Combined Hepatocellular Cholangiocarcinoma.

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a primary liver tumor with neoplastic components of both hepatocytic and cholangiocytic differentiation. This unique neoplasm is gaining increasing recognition due to the intriguing pathology, tumor biology, and clinical behavior. It also poses challenges in diagnosis, treatment, and research, largely because of its histological and phenotypic diversity that lead to confusion in terminology and classification. There have been efforts attempting to unify the terminology of this neoplasm recently. Advances in investigation in various aspects have also been made. This review aims to update the terminology, classification, and clinical and pathological characteristics of cHCC-CCA.

Relationship Between the Immunodetection of Alpha-Smooth Muscle Actin and the Aggressiveness of Mammary Papillar Tumors in Female Dog

Papillary carcinoma is a mammary neoplasia of women and female dogs characterized by papillary fibrovascular projections lined by epithelial cells. Evaluation on the biology of these tumors can be done by immunohistochemistry through detection of alpha-smooth muscle actin protein in the papillary myoepithelium, which lacks such a molecule during malignant proliferations. Thus, this study aimed at determining the malignancy degree of papillary mammary tumors of female dogs by immunohistochemistry. Twenty samples of mammary neoplastic tissues collected from female dogs treated in the Veterinary Hospital at FCAV were evaluated by Hematoxylin and Eosin staining (H&amp;E) and tumor cells were immunolabelled with monoclonal antibody to alpha-smooth muscle actin (α-SMA). Five out of 20 cases showed positive immunolabeling greater than 10% of the total immunolabeling. The remaining fourteen cases presented immunostaining lesser than 10% showing decrease or absence of α-SMA labeling in the myoepithelium of the papilla tumors. All those cases in which immunostained cell was over 10% of the neoplasm (5 immunostains of 20 total cases) were classified as benign whereas those below 10% of immunostained in the slid were considered as malignant. Therefore, immunohistochemistry played an essential role in differentiating benign and malignant papillary tumors of bitches as already described for female. Tumor classification by conventional methods, such as H&amp;E staining, can lead to erroneous interpretations on the real biological behavior of the papillary mammary tumor.

The role of the multi‐drug resistance 1, p53, b cell lymphoma 2, and bcl 2‐associated X genes in the biologic behavior and chemotherapeutic resistance of canine transmissible venereal tumors

Canine transmissible venereal tumors (CTVTs) generally have different cytomorphologic subtypes and phases of progression. Some tumors have variable biologic behavior including a progressive increase in tumor aggressiveness and variable responses to chemotherapy. This behavior is partially due to high p-glycoprotein expression by tumor cells, which leads to the expulsion of chemotherapeutic drugs. Other possible causes include changes in pro- and anti-apoptotic genes from the BCL-2 family and DNA repair systems, which are associated with the p53 gene family. We aimed to determine the relative expression of the multi-drug resistance 1 (MDR1), p53, b-cell lymphoma 2 (BCL2), and bcl 2-associated X (BAX) genes in CTVT before and after therapy and establish a relationship with treatment responses, cytomorphologic patterns, and tumor progression identified with histopathology. RT-qPCR was performed on 21 CTVT tumor samples before and after initiating chemotherapy to determine specific gene expression. Normal canine testicular tissue was used as a negative control for all experiments. MDR1 expression was decreased before and after initiating vincristine therapy in CTVT tumor tissues compared with normal canine testicular tissue; p53 and BAX were overexpressed at both time points compared with normal tissue, and no statistical differences were seen between the different morphologic types. However, BAX expression was decreased in the group with quick therapeutic responses but was still overexpressed compared with normal testicular tissue. In the group with the slowest chemotherapeutic responses, BCL2 was overexpressed. The findings of this study showed a relative increase in MDR1 gene expression in response to chemotherapy and higher expression in plasmacytoid CTVTs compared with the other cytomorphologic patterns. BCL2 overexpression was related to a favorable prognosis, and p53, BAX, and BCL2 were expressed independent of the cytomorphologic CTVT type. All of the genes were expressed independent of tumor progression, as noted on histopathology.

Recurrence in Patients Achieving Pathological Complete Response After Neoadjuvant Treatment for Advanced Pancreatic Cancer.

The aim of this study was to characterize the patterns and treatment of disease recurrence in patients achieving a pathological complete response (pCR) following neoadjuvant chemoradiation for advanced pancreatic ductal adenocarcinoma (PDAC). A pCR is an independent predictor for improved survival in PDAC. However, disease recurrence is still observed in these patients. Patients with advanced PDAC who were treated with neoadjuvant therapy and had a pCR were identified between 2009 and 2017. Overall survival (OS) was determined from the initiation of neoadjuvant, disease-free survival (DFS) from the date of surgery, and post-recurrence survival (PRS) from the date of recurrence. Factors associated with recurrence were analyzed using a Cox-regression model. Of 331 patients with borderline resectable or locally advanced PDAC, 30 achieved a pCR following neoadjuvant treatment and pancreatectomy. The median DFS for pCR patients was 29 months and OS 76 months. Recurrence was observed in 14 patients. No clinicopathologic or treatment characteristics were associated with survival. The median PRS following recurrence was 25 months. Treatment following recurrence included chemotherapy, radiation or ablation, and surgical resection. Hepatectomy or completion pancreatectomy was accomplished in 2 patients that remain alive 13 and 62 months, respectively, following metastasectomy. A pCR following neoadjuvant therapy in patients with advanced PDAC is associated with remarkable survival, although recurrence occurs in about half of patients. Nevertheless, patients with pCR and recurrence respond well to treatment and survival remains encouraging. Advanced molecular characterization and longitudinal liquid biopsy may offer additional assistance with understanding tumor biologic behavior after achieving a pCR.

Histopathological growth patterns and positive margins after resection of colorectal liver metastases

BackgroundHistopathological growth patterns (HGPs) of colorectal liver metastases (CRLM) may be an expression of biological tumour behaviour impacting the risk of positive resection margins. The current study aimed to investigate whether the non-desmoplastic growth pattern (non-dHGP) is associated with a higher risk of positive resection margins after resection of CRLM. MethodsAll patients treated surgically for CRLM between January 2000 and March 2015 at the Erasmus MC Cancer Institute and between January 2000 and December 2012 at the Memorial Sloan Kettering Cancer Center were considered for inclusion. ResultsOf all patients (n = 1302) included for analysis, 13% (n = 170) had positive resection margins. Factors independently associated with positive resection margins were the non-dHGP (odds ratio (OR): 1.79, 95% confidence interval (CI): 1.11–2.87, p = 0.016) and a greater number of CRLM (OR: 1.15, 95% CI: 1.08–1.23 p < 0.001). Both positive resection margins (HR: 1.41, 95% CI: 1.13–1.76, p = 0.002) and non-dHGP (HR: 1.57, 95% CI: 1.26–1.95, p < 0.001) were independently associated with worse overall survival. ConclusionPatients with non-dHGP are at higher risk of positive resection margins. Despite this association, both positive resection margins and non-dHGP are independent prognostic indicators of worse overall survival.

Sellar region: Magnetic resonance imaging assessment of uncommon tumors and pseudotumors

ObjectiveTo show the usefulness of magnetic resonance imaging in the anatomic and pathologic characterisation of the sellar region, emphasising the differential diagnosis of uncommon non-adenomatous tumors and pseudotumors studied in our institution. ConclusionThe sellar region is a complex anatomic space with diverse types of tissues from which a wide spectrum of diseases can arise. Magnetic resonance imaging's high tissue resolution and ability to characterise the patterns of tumor growth and biological behaviour make it the best imaging technique to study this region.

95P - Anatomical resections improve relapse-free survival in patients with KRAS/NRAS/BRAF- mutated colorectal liver metastases

BackgroundThe type of liver resection (anatomical resection, AR or nonanatomical resection, NAR) for colorectal liver metastases (CRLM) is subject to debate. The debate may persist because some certain prognostic implications, associated with worse biological behavior of tumors, have been overlooked. The aim of this study was to explore the characteristics of patients who would benefit more from the performance of AR. Methods475 patients who underwent hepatic resection of CRLM were included and stratified by KRAS/NRAS/BRAF mutational status. The Kaplan-Meier method was applied in relapse-free survival (RFS), and the Cox proportional hazards model was used to identify independent predictors of prognosis in multivariable analysis. ResultsAmong all 475 patients, 154 (32.4%) underwent AR and 321 (67.6%) underwent NAR. 1-, 2-, and 3-year RFS for the entire cohort were 63.0%, 40.6%, and 31.2% respectively. In the cohort of patients with KRAS/NRAS/BRAF mutated tumors, patients who underwent AR had a markedly improved median RFS compared with patients who underwent NAR (24.1 VS. 12.9 months, P = 0.005). Upon the multivariable analyses, the performance of AR (hazard ratios=0.562; 95% CI 0.370-0.854, P = 0.007) remained prognostic independently for a superior RFS. In contrast, in the cohort of patients with KRAS/NRAS/BRAF wild-type tumors, patients who underwent AR had a comparable median RFS compared with those who underwent NAR (24.9 VS. 20.3 months, P = 0.901). ConclusionsPatients with KRAS/NRAS/BRAF mutated tumors may benefit more from the performance of AR than from the performance of NAR. Legal entity responsible for the studyZhongshan Hospital. FundingThe National Natural Science Foundation of China. DisclosureAll authors have declared no conflicts of interest.

Revised criteria for diagnosis of NIFTP reveals a better correlation with tumor biological behavior.

The recent reclassification of a follicular variant of papillary thyroid carcinoma (FVPTC), subset as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), aims to avoid overtreatment of patients with an indolent lesion. The diagnosis of NIFTP has recently been revisited using more rigid criteria. This study presents histological and molecular findings and a long clinical follow-up of 94 FVPTC, 40 cases of follicular adenoma (FTA) and 22 cases of follicular carcinoma (FTC) that were classified before the advent of the NIFTP reclassification. All slides were reviewed using these rigid criteria and analysis of numerous sections of paraffin blocks and reclassified as 7 NIFTPs, 2 EFVPTCs, 29 infiltrative FVPTC (IFVPTCs), 57 invasive EFVPTC (I-EFVPTCs), 39 FTAs and 22 FTCs. Remarkably, EFVPTC and NIFTP patients were all free of disease at the end of follow-up and showed no BRAF mutation. Only one NIFTP sample harbored mutations, an NRAS Q61R. PAX8/PPARG fusion was found in I-EFVPTCs and FTC. Although additional studies are needed to identify a specific molecular profile to aid in the diagnosis of lesions with borderline morphological characteristics, we confirmed that the BRAF V600E mutation is an important tool to exclude the diagnosis of NIFTP. We also show that rigorous histopathological criteria should be strongly followed to avoid missing lesions in which more aggressive behavior is present, mainly via the analysis of capsule or vascular invasion and the presence of papillary structures.

Research Progress of the Functional Role of ACK1 in Breast Cancer.

ACK1 is a nonreceptor tyrosine kinase with a unique structure, which is tightly related to the biological behavior of tumors. Previous studies have demonstrated that ACK1 was involved with multiple signaling pathways of tumor progression. Its crucial role in tumor cell proliferation, apoptosis, invasion, and metastasis was tightly related to the prognosis and clinicopathology of cancer. ACK1 has a unique way of regulating cellular pathways, different from other nonreceptor tyrosine kinases. As an oncogenic kinase, recent studies have shown that ACK1 plays a critical regulatory role in the initiation and progression of tumors. In this review, we will be summarizing the structural characteristics, activation, and regulation of ACK1 in breast cancer, aiming to deeply understand the functional and mechanistic role of ACK1 and provide novel therapeutic strategies for breast cancer treatment.

Platelets and Hepatocellular Cancer: Bridging the Bench to the Clinics.

Growing interest is recently being focused on the role played by the platelets in favoring hepatocellular cancer (HCC) growth and dissemination. The present review reports in detail both the experimental and clinical evidence published on this topic. Several growth factors and angiogenic molecules specifically secreted by platelets are directly connected with tumor progression and neo-angiogenesis. Among them, we can list the platelet-derived growth factor, the vascular endothelial growth factor, the endothelial growth factor, and serotonin. Platelets are also involved in tumor spread, favoring endothelium permeabilization and tumor cells’ extravasation and survival in the bloodstream. From the bench to the clinics, all of these aspects were also investigated in clinical series, showing an evident correlation between platelet count and size of HCC, tumor biological behavior, metastatic spread, and overall survival rates. Moreover, a better understanding of the mechanisms involved in the platelet–tumor axis represents a paramount aspect for optimizing both current tumor treatment and development of new therapeutic strategies against HCC.

The association between 18F-fluorodeoxyglucose PET intratumoral metabolic heterogeneity and pathological parameters in non-small cell lung cancer.

The aim of this study was to evaluate the association between intratumoral metabolic heterogeneity on F-fluorodeoxyglucose (F-FDG) PET imaging and the pathological type, differentiation and T stage of non-small cell lung cancer (NSCLC). Two hundred thirty-four consecutive patients who were performed pretreatment F-FDG PET/computed tomography and pathologically diagnosed as NSCLC were assessed retrospectively. Metabolic heterogeneity factor (MHF) derived from the volume-threshold function from 40 to 90% was calculated for primary lesions. The association between MHF and the pathological type, differentiation and T stage of NSCLC were analyzed, respectively. The MHF values were statistically different among pathological types, differentiation and T stages (F = 17.611, 23.932 and 11.082, P all < 0.001). MHF showed a stepwise increase with the reduced degree of differentiation and increase of T stage. The trend analysis presented a strong positive relationship between MHF and T stage (P < 0.05), but a correlated inversely and strongly relationship was demonstrated between MHF and diffferentiation (P < 0.001). Moreover, multivariate ordinal logistic regression analysis showed that MHF was independently associated with tumor T stage and differentiation after adjusting for clinical factors. MHF showed high association with pathological parameters, which can be used to accurately predict the biological behaviors of tumors from the molecular level thus to provide important biological information for tumor diagnosis and treatment.

CircPTN sponges miR-145-5p/miR-330-5p to promote proliferation and stemness in glioma

BackgroundGrowing evidences indicate that circular RNAs (circRNAs) play an important role in the regulation of biological behavior of tumor. We aim to explore the role of circRNA in glioma and elucidate how circRNA acts.MethodsReal-time PCR was used to examine the expression of circPTN in glioma tissues and normal brain tissues (NBT). Assays of dual- luciferase reporter system, biotin label RNA pull-down and FISH were used to determine that circPTN could sponge miR-145-5p and miR-330-5p. Tumor sphere formation assay was performed to determine self- renewal of glioma stem cell (GSCs). Cell counting Kit-8 (CCK8), EdU assay and flow cytometry were used to investigate proliferation and cell cycle. Intracranial xenograft was established to determine how circPTN impacts in vivo. Tumor sphere formation assay was performed to determine self- renewal of glioma stem cell (GSCs).ResultsWe demonstrated circPTN was significantly higher expression in glioma tissues and glioma cell lines, compared with NBT and HEB (human astrocyte). In gain- and loss-of-function experiments, circPTN significantly promoted glioma growth in vitro and in vivo. Furthermore, we performed dual-luciferase reporter assays and RNA pull-down assays to verify that circPTN acts through sponging miR-145-5p and miR-330-5p. Increasing expression of circPTN rescued the inhibition of proliferation and downregulation of SOX9/ITGA5 in glioma cells by miR-145-5p/miR-330-5p. In addition, we found that circPTN promoted self-renewal and increased the expression of stemness markers (Nestin, CD133, SOX9, and SOX2) via sponging miR-145-5p. Moreover, this regulation was disappeared when circPTN binding sites in miR-145-5p were mutated.ConclusionsOur results suggest that circPTN is an oncogenic factor that acts by sponging miR-145-5p/miR-330-5p in glioma.

Papillary Tumor of the Pineal Region: Systematic Review and Analysis of Prognostic Factors.

Clinical outcomes and biological behavior of papillary tumors of the pineal region (PTPR) are still under investigation. The best therapeutic strategy has not been defined. To perform a comprehensive patient-level analysis of all PTPR cases and identify their clinical features, treatment options, and prognostic factors. A search of the medical databases for case series and reports on PTPRs from January 2003 to June 2017 was performed. Data addressing PTPR's clinical presentation, imaging, treatment, and histological features were. Variables associated with the primary outcome of 36-mo survival were identified through Cox regression models. The initial search yielded 1164 studies, of which 71 were included (60 case reports and 11 case series), containing 177 patients (mean age 33.0±15.3 yr and 53.2% male). Intracranial hypertension and hydrocephalus prevailed as the clinical picture. Surgery was performed on 82.0% and gross total resection (GTR) was achieved on 71.4%. A total of 56.8% recurred after a median 29 mo (quartiles 10.5-45.5). The 36-mo survival rate was 83.5% (95% confidence interval [CI] 76.2-89.2%). Good functional outcomes (Glasgow Outcome Scale 4/5) were observed in 60.0%. The variables of interest were inconsistently reported and the multivariable analysis final sample was 133 patients. After adjustment for age, tumor size (each additional centimeter, hazard ratio [HR] 1.99, 95% CI 1.12-3.53, P=.019) and surgical treatment (HR 0.16, 95% CI 0.05-0.45, P=.001) were associated with 36-mo survival. Tumor size and surgery are associated with improvement in 36-mo survival. We did not observe any significant benefits from GTR or adjuvant treatments.

Role of chemokine receptors in thyroid cancer and immunotherapy.

Inflammation is currently regarded as an essential component of malignancies. It is now known that the tumor microenvironment may profoundly influence the biological behavior of cancer cells and ultimately the patient's outcome. Chemokine and their receptor play a major role in determining the immune phenotype of the cells infiltrating the thyroid tumor microenvironment. Experimental evidence shows that both normal and cancer thyroid cells express specific chemokine receptors. The expression of at least some of these receptors exerts several biological effects, which influence the course of the disease. The present review article will take into account the role of the most studied chemokine receptors (CXCR1, CXCR2, CXCR3, CXCR4, CXCR7, DARC, CCR3, CCR6 and CCR7) in the context of thyroid cancer. This review will focus on current knowledge provided by in vitro and in vivo studies specifically performed on thyroid cancer including (i) expression of chemokine receptors in normal and cancer thyroid cells; (ii) role of chemokine receptors in affecting the biological behavior of thyroid tumors including the metastatic process; (iii) current knowledge about immunotherapies through targeting of chemokine receptors in thyroid cancer.

New advances in comprehensive treatment for pancreatic cancer

Pancreatic cancer is a highly digestive system malignancy with an extremely poor prognosis. Although the rapid improvements of surgical technique have resulted in the increase in the resection rate and the significant decline in peri-operative morbidity and mortality, the prognosis of pancreatic cancer remains far from satisfying. As the understanding of tumor biological behavior deepens, the treatment strategy of pancreatic cancer has been changed from surgery first to multidisciplinary team (MDT) based comprehensive management including surgery, chemotherapy, radiotherapy and others. In the past decade, MDT modality has been employed widely in high volume pancreatic center and has improved the management of pancreatic cancer. Here, the authors reviewed the recent advances in systematic treatment for pancreatic cancer, with an aim to provide new horizons of optimal management. Key words: Pancreatic neoplasms; Pancreatic cancer; Multidisciplinary team; Comprehensive treatment; Chemotherapy; Neoadjuvant therapy