IntroductionThe somatostatin receptor (SSTR) standardized uptake value (SUVmaxsstr) obtained by [68Ga]Ga-edotreotide positron emission tomography-computed tomography ([68Ga]Ga-SSTR PET/CT) helps recognize patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) who are at a high risk for adverse outcomes. This observational cohort study was conducted to verify whether the SSTR representative tumor volume (RTVsstr) can provide incremental prognostic information over conventional PET/CT parameters in patients with metastatic disease.MethodsWe retrospectively evaluated patients (48% female) with metastatic GEP-NETs who underwent [68Ga]Ga-SSTR PET/CT between January 2022 and November 2023. The mean SUVmaxsstr, mean RTVsstr (cm3; 42% threshold), and total RTVsstr were recorded. Thereafter, patients were followed up for 22.9 (range: 8-42) months. The PET/CT results were compared to the progression free survival (PFS).ResultsSixty patients (59 ± 5 years) were enrolled. Only the mean and total RTVsstr values were predictive in the multivariate analysis. Kaplan-Meier survival analysis for both the mean and total RTVsstr demonstrated a significantly better PFS in patients presenting with lower than greater values (P = 0.001 and P = 0.007, respectively; log-rank test). SUVmaxsstr was not appropriate for predicting PFS.ConclusionThe mean or total RTVsstr represents a valuable volumetric parameter able to predict outcomes in patients with GEP-NETs that are metastatic at onset. The degree of the SSTR representative tumor burden, rather than the maximal SSTR representation at single voxel, has a predominant value for influencing the response to therapy in this cohort.

This feasibility study evaluated the psychological status of patients with differentiated thyroid cancer (DTC) before, during, and 40 days after administration of I-131 radionuclide therapy (RAI). We investigated the appropriateness of providing patient a comprehensive psychological assessment in an isolation ward. Thirty consecutive patients (Study Group; SG) who received RAI were enrolled. The tools used were the Hospital Anxiety and Depression Scale (HADS) at three different moments, and the Coping Responses Inventory (CRI) at baseline for each patient. A supportive approach was also implemented. Data were collected at the first specialist visit, at the day of admission, and at 40 days follow-up visit. A matched cohort of patients (Control Group; CG), who did not receive psycho-oncological counseling, was retrospectively studied only about their medical needs and requests. Staff exposure to radiation was also compared during SG and CG hospitalization, to assess a possible reduction of radiological risk for them. A significant difference between the basal, intermediate, and final psychological status was observed (p < 0.0001), which was found to be irrespective of the induced hypothyroidism. Patients showed a significant worsening of their status in terms of anxiety and depression after the consent, but it improved 40 days after treatment. Repeated measures analysis showed a similar trend in patients’ psychological status over this period. At hospital discharge, patients showed indirect signs of increased well-being. CG required more nursing and medical interventions. Staff exposure was significantly lower during hospitalization of SG as compared to CG. This study demonstrates that timed psychological evaluation and appropriate support may help to reduce anxiety and depression of patients receiving a diagnosis of cancer and undergoing RAI. Moreover, an improvement of workplace safety was recorded.

Il carcinoma differenziato della tiroide (CDT) è la più frequente neoplasia endocrina maligna. Nonostante la prognosi del CDT sia eccellente, alcuni pazienti presentano forme aggressive di malattia talora metastatiche fin dall’esordio (metastasi linfonodali locoregionali presenti nel 20–60

Background: The unexpected detection of axillary lymphadenopathy (AxL) in cancer patients (pts) represents a real concern during the COVID-19 vaccination era. Benign reactions may take place after vaccine inoculation, which can mislead image interpretation in patients undergoing F-18-FDG, F-18-Choline, and Ga-68-DOTATOC PET/CT. They may also mimic loco-regional metastases or disease. We assessed PET/CT findings after COVID-19 first dose vaccination in cancer patients and the impact on their disease course management. Methods: We evaluated 333 patients undergoing PET/CT (257 F-18-FDG, 54 F-18-Choline, and 23 Ga-68 DOTATOC) scans after the first vaccination with mRNA vaccine (Pfizer-BioNTech) (study group; SG). The uptake index (SUVmax) of suspected AxL was defined as significant when the ratio was > 1.5 as compared to the contralateral lymph nodes. Besides, co-registered CT (Co-CT) features of target lymph nodes were evaluated. Nodes with aggregate imaging positivity were further investigated. Results: Overall, the prevalence of apparently positive lymph nodes on PET scans was 17.1% during the vaccination period. 107 pts of the same setting, who had undergone PET/CT before the COVID-19 pandemic, represented the control group (CG). Only 3 patients of CG showed reactive lymph nodes with a prevalence of 2.8% (p < 0.001 as compared to the vaccination period). 84.2% of SG patients exhibited benign characteristics on co-CT images and only 9 pts needed thorough appraisal. Conclusion: The correct interpretation of images is crucial to avoid unnecessary treatments and invasive procedures in vaccinated cancer pts. A detailed anamnestic interview and the analysis of lymph nodes’ CT characteristics, after performing PET/CT, may help to clear any misleading diagnosis.

Background: Oncogene-driven NSCLC is usually treated with targeted therapies using tyrosine kinase inhibitors (TKIs) to inhibit oncogene downstream signaling pathways, affecting tumor survival and proliferation. EGFR- and KRAS-mutant NSCLCs are the most represented subtypes, and they are treated in clinical practice with oncogene-targeting drugs in the first and second line, respectively. Unfortunately, the development of oncogene-independent resistant clones limits TKI efficacy. Here, we used non-oncogene addiction (NOA) as an innovative therapeutic strategy to target other essential proteins that support changes in tumor phenotype. Specifically, we tested, for the first time, a combination of inhibitors, namely ATR, involved in DNA damage response, and pyruvate dehydrogenase kinases (PDKs), involved in energy metabolism. Methods: Sensitive PC9 and the corresponding EGFR-TKI-resistant PC9/OR, EGFR-mutant H1975, and KRAS-mutant A549 NSCLC cells, were treated with TKIs (osimertinib and selumetinib, respectively). In parallel, cells were exposed to two combination regimens: one using the TKI with an ATR inhibitor and the other one combining the two selected NOA inhibitors (ATR inhibitor, M4344; and PDK inhibitor, DCA). Results: The effect of these two combined approaches, compared to TKI alone, produced similar results in terms of cell proliferation, cell death, and migration. Thus, depending on tumor biology, selecting between the proposed therapeutic strategies will be different, to maximize tumor response. Conclusions: The major translational relevance of this study is to exploit new targets for the development of innovative and improved therapeutic strategies with NOA drugs, over combinations including target genes within the oncogene pathway, to overcome resistance to TKI therapies in patients with NSCLC who are oncogene-addicted.

Background We retrospectively aimed to assess the prognostic significance of somatostatin receptor (SSTR) standardized uptake value (SUVmax sstr ), SSTR representative tumor volume (RTV sstr ) and total lesion SSTR expression (TL sstr ) obtained by [ 68 Ga]Ga-edotreotide PET/CT ([ 68 Ga]Ga-SSTR PET/CT) in patients with primary gastroenteropancreatic neuroendocrine tumors (GEP-NET) before surgery. Material and Methods We analyzed patients who underwent [ 68 Ga]Ga-SSTR PET/CT 3-6 weeks before surgery from February 2020 to April 2022. The mean SUVmax sstr value, the RTV sstr (cm3; 42% threshold) and the TL sstr (g) were registered. Thereafter the patients were followed up 10.3 months (range 3-27). The PET/CT results were compared to the event free survival (EFS). Results Forty-two patients (61 ± 13 years) have been enrolled. At multivariate analysis only RTV sstr values were predictive. The Kaplan-Meier survival analysis for RTV sstr showed a significant better EFS in patients presenting lower values as compared to those having greater ( P = .003, log-rank test). SUVmax sstr was not suitable for predicting EFS, TL sstr mildly. Conclusion RTV sstr represents a valuable volumetric parameter able to predict the outcome in GEP-NET patients who underwent surgery. The magnitude of the SSTR representative tumor burden holds a predominant value for determining the response to therapy in GEP-NET patients before surgery, rather than the maximal SSTR representation at single voxel.

Objectives: unexpected detection of axillary lymphadenopathy (AxL) in cancer patients (Pts) represents a real concern during COVID-19 vaccination era. Benign reactions may take place after vaccine inoculation, confounding image interpretation in patients undergoing F-18-FDG, F-18-Choline and Ga-68-DOTATOC PET/CT. It may simulate loco-regional metastases/disease. To assess PET/CT findings after COVID-19 vaccination in cancer patients and the consequent impact on their management. Methods: we evaluated 333 patients undergoing PET/CT (257 F-18-FDG, 54 F-18-Choline and 23 Ga-68 DOTATOC) scans after first vaccination with mRNA vaccine (Pfizer-BioNTech). Uptake index (SUVmax) of suspected AxL was defined significant when the ratio >1.5 as compared to the contralateral inoculation site. Besides, co-registered CT (Co-CT) features of target lymph-nodes were evaluated. Nodes with aggregate positivity were further investigated.Results: overall, the prevalence of apparently positive lymph-nodes on PET scans was 17.1% during vaccination era. 107 Pts had undergone PET/CT before COVID-19 pandemic and only 3 shown reactive lymph-nodes with a prevalence of 2.8% (p<0.001 as compared to vaccination era). 84.2% exhibited benign characteristics on Co-CT images and only 9 Pts needed additional appraisal. Conclusions: the correct interpretation of images is crucial to avoid unnecessary management changes and to rule out invasive procedures in cancer Pts undergoing diagnostics. An accurate anamnestic interview and the precise assessment of nodes’ Co-CT characteristics when performing PET/CT may help to address the diagnostic hypothesis.

Mathematical modeling constitutes an emerging area of oncological research aiming to predict spatial and temporal evolution of tumors, by describing many different phenomena, which occur at different scales. Among these, modeling at the macroscopic scale has an interesting potential of application, when applied in a framework where actual diagnostic imaging is used to identify the metabolic tumor volume undergoing proliferation. Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of lymphocyte that is responsible for producing antibodies. The most common form of Non-Hodgkin lymphoma among adults, DLBCL can arise in any part of the body and may play a very aggressive malignancy. This paper aims to enforce a mass transfer modeling approach in order to gain deeper insight into the dynamics of tumor growth at the tissue scale and to develop a predictive, quantitative method for each patient at hand. A cohort of 18 patients has been successfully enrolled to validate the model. Results confirm that tumor proliferation, at the macroscopic scale, scores many nonlinear features, and show that the proposed model could be used by oncologists as a decision support tool towards personalized treatment optimization of solid tumors.

OBJECTIVE:This study aimed to evaluate the association between polypharmacy and delirium, the association of specific drug categories with delirium, and the differences in drug-delirium association between medical and surgical units and according to dementia diagnosis.METHODS:Data were collected during 2 waves of Delirium Day, a multicenter delirium prevalence study including patients (aged 65 years or older) admitted to acute and long-term care wards in Italy (2015-2016); in this study, only patients enrolled in acute hospital wards were selected (n = 4,133). Delirium was assessed according to score on the 4 "A's" Test. Prescriptions were classified by main drug categories; polypharmacy was defined as a prescription of drugs from 5 or more classes.RESULTS:Of 4,133 participants, 969 (23.4%) had delirium. The general prevalence of polypharmacy was higher in patients with delirium (67.6% vs 63.0%, P = .009) but varied according to clinical settings. After adjustment for confounders, polypharmacy was associated with delirium only in patients admitted to surgical units (OR = 2.9; 95% CI, 1.4-6.1). Insulin, antibiotics, antiepileptics, antipsychotics, and atypical antidepressants were associated with delirium, whereas statins and angiotensin receptor blockers exhibited an inverse association. A stronger association was seen between typical and atypical antipsychotics and delirium in subjects free from dementia compared to individuals with dementia (typical: OR = 4.31; 95% CI, 2.94-6.31 without dementia vs OR = 1.64; 95% CI, 1.19-2.26 with dementia; atypical: OR = 5.32; 95% CI, 3.44-8.22 without dementia vs OR = 1.74; 95% CI, 1.26-2.40 with dementia). The absence of antipsychotics among the prescribed drugs was inversely associated with delirium in the whole sample and in both of the hospital settings, but only in patients without dementia.CONCLUSIONS:Polypharmacy is significantly associated with delirium only in surgical units, raising the issue of the relevance of medication review in different clinical settings. Specific drug classes are associated with delirium depending on the clinical setting and dementia diagnosis, suggesting the need to further explore this relationship.

Despite the significant recent advances in clinical practice, gastric cancer (GC) represents a leading cause of cancer-related deaths in the world. In fact, occurrence of chemo-resistance still remains a daunting hindrance to effectiveness of the current approach to GC therapy. There is accumulating evidence that a plethora of cellular and molecular factors is implicated in drug-induced phenotypical switching of GC cells. Among them, epithelial-mesenchymal transition (EMT), autophagy, drug detoxification, DNA damage response and drug target alterations, have been reported as major determinants. Intriguingly, resistant GC phenotype may be the result of GC cell-induced tumor microenvironment (TME) remodeling, which is currently emerging as a key player in promoting drug resistance and overcoming cytotoxic effects of drugs. In this review, we discuss the possible mechanisms of drug resistance and their involvement in determining current GC therapies failure.

Radium-223 dichloride (223Ra) is the first, recently approved, α-particle-emitting radiopharmaceutical for the treatment of patients with bone metastases in castration-resistant prostate cancer (CRPC) and no evidence of visceral metastases. We explored MEDLINE, relevant congresses, and websites for data on 223Ra and prostate cancer therapies, focusing on therapeutic strategies and timing, bone metastases, and diagnostic assessment. 223Ra represents the only bone-targeting agent that has significantly extended patients’ overall survival while reducing pain and symptomatic skeletal events. Unlike other radiopharmaceuticals, such as strontium-89 and samarium-153 EDTMP, 223Ra (11.4-days half-life) has shown a high biological efficiency mainly due to its short penetration range. These features potentially allow reduced bone marrow toxicity and limit undue exposure. 223Ra has been validated under the product name Xofigo® by the US Food and Drug Administration and the European Medicines Agency. Patient selection, management, and treatment sequencing is recommended to be discussed in the context of a multidisciplinary environment, including oncology, urology, nuclear medicine, and radiation therapy physicians. No consensus has been achieved regarding the optimal timing and its administration as single agent or in combination with zoledronic acid or chemotherapy, so far. This review aims to provide a rationale for the use of 223Ra in treating metastases from CRPC, highlighting the crucial role of a multidisciplinary approach, the disputed inclusion and exclusion criteria on the basis of agencies regulations, and the value of diagnostics for therapy assessment.

Pancreatic organogenesis is a multistep process that requires the cooperation of several signaling pathways. In this context, the role of pancreatic mesenchyme is important to define the epithelium development; nevertheless, the precise space–temporal signaling activation still needs to be clarified. This study reports a dissection of the pancreatic embryogenesis, highlighting the molecular network surrounding the epithelium–mesenchyme interaction. To investigate this crosstalk, pancreatic epithelium and surrounding mesenchyme, at embryonic day 10.5, were collected through laser capture microdissection (LCM) and characterized based on their global gene expression. We performed a bioinformatic analysis to hypothesize crosstalk interactions, validating the most promising genes and verifying the precise localization of their expression in the compartments, by RNA in situ hybridization (ISH). Our analyses pointed out also the c-Met gene, a very well-known factor involved in stimulating motility, morphogenesis, and organ regeneration. We also highlighted the potential crosstalk between Versican (Vcan) and Syndecan4 (Sdc4) since these genes are involved in pancreatic tissue repair, strengthening the concept that the same signaling pathways required during pancreatic embryogenesis are also involved in tissue repair. This finding leads to novel strategies for obtaining functional pancreatic stem cells for cell replacement therapies.

This review aimed to provide an overview on findings from metabolic imaging modalities such as bone scintigraphy and positron emission tomography–computed tomography (PET/CT) in musculoskeletal lesions. It is conceivable that methods assessing metabolism of bone tumors, combined with the morphological assessment, could enhance the possibility for a personalized therapy with particular emphasis to malignant neoplasms.

Sheep is a relevant large animal model that is frequently used to test innovative tissue engineering (TE) approaches especially for bone reconstruction. Mesenchymal stem cells (MSCs) are used in TE applications because they represent key component of adult tissue repair. Importantly, MSCs from different species show similar characteristics, which facilitated their application in translational studies using animal models. Nowadays, many researches are focusing on the use of ovine mesenchymal stem cells (oMSCs) in orthopedic preclinical settings for regenerative medicine purposes. Therefore, there is a need to amplify our knowledge on the mechanisms underlying the behaviour of these cells. Recently, several studies have shown that MSC function is largely dependent on factors that MSCs release in the environment, as well as, in conditioned medium (CM). It has been demonstrated that MSCs through autocrine and paracrine signals are able to stimulate proliferation, migration, and differentiation of different type of cells including themselves. In this study, we investigated the effects of the CM produced by oMSCs on oMSCs themselves and we explored the signal pathways involved. We observed that CM caused an enhancement of oMSC migration. Furthermore, we found that CM increased levels of two membrane proteins involved in cell migration, Aquaporin 1 (AQP1), and C‐X‐C chemokine receptor type 4 (CXCR4), and activated Akt and Erk intracellular signal pathways. In conclusion, taken together our results suggest the high potential of autologous CM as a promising tool to modulate behaviour of MSCs thus improving their use in therapeutically approaches.

BACKGROUND:In-vivo imaging of dopamine transporter (DAT), a reliable marker of degeneration of nigrostriatal dopaminergic innervation, has gained increasing interest in preclinical neurodegenerative research for studying disease mechanisms and testing new therapeutic strategies. We assessed the feasibility and the reliability of in vivo and ex vivo quantification of Methyl (3S,4S,5R)-8-(3-fluoropropyl)-3-(4-iodophenyl)-8-azabicyclo[3.2.1]octane-4-carboxylate ([123I]FP-CIT) binding to striatal DAT sites in mouse brain.METHODS:Dedicated small animal single-photon emission computed tomography (SPECT) images of [123I]FP-CIT binding were obtained in 3 groups of healthy mice: untreated (N.=6), pre-treated with lugol solution (N.=4), and pre-treated with selective dopamine transporter uptake inhibitor GBR12909 (N.=4). Ex-vivo autoradiography studies were performed at the end of SPECT studies with phosphor image system in 4 out of the 6 untreated mice and in all mice pre-treated with lugol. Regions of interest were defined over the striatum. The specific binding (SB) was calculated using the cerebral cortex as reference region.RESULTS:SPECT images in untreated mice showed high [123I]FP-CIT uptake in the striatum and extracerebral regions. Lugol pretreatment improved striatal images quality decreasing salivary and thyroid glands uptake. SB was higher (P<0.0001) in mice pre-treated with lugol (5.97±0.60) than in untreated mice (2.25±0.28). Autoradiography showed similar SB findings in untreated (2.27±0.33) and lugol-treated (4.27±0.57) mice (P<0.0001). In-vivo striatal 123I-FP-CIT SB and ex-vivo striatal 123I-FP-CIT SB were significantly correlated (r=0.87; P<0.0001). SPECT competition studies showed a significant (P<0.0001) reduction of [123I]FP-CIT SB in the striatum after GBR12909.CONCLUSIONS:We demonstrated the feasibility of [123I]FP-CIT imaging of the normal mouse brain using small-animal SPECT without pinhole collimators. The reliability of quantitative measurement of striatal [123I]FP-CIT SB is supported by competition studies showing measurable inhibition of uptake induced by GBR12909 and by the strong correlation between in vivo and ex vivo striatal [123I]FP-CIT SB. Our data also demonstrate that pre-treatment with lugol might improve striatal [123I]FP-CIT SB in mice.

OBJECTIVE:We evaluated the prognostic impact of quantitative assessment by maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and tumour lesion glycolysis (TLG) on [F-18] FDG PET/CT for patients with peritoneal carcinomatosis from epithelial ovarian cancer (EOC).METHODS:Thirty-one patients with EOC underwent PET/CT for an early restaging after cytoreductive surgery, having been diagnosed with carcinomatosis (before chemotherapy). The SUVmax, MTV (cm3; 42% threshold) and TLG (g) were registered on residual peritoneal lesions. The patients were followed up 20±12months thereafter. The PET/CT results were compared to overall survival (OS).RESULTS:The Kaplan-Meier survival analysis for the SUVmax did not reveal significant differences in OS (p=0.48). The MTV survival analysis showed a significant higher OS in patients presenting with a higher tumour burden than those with less tumour burden (p=0.01; 26 vs. 14 months), whereas TLG exhibited a similar trend though not significant (p=0.06). Apart from chemo-resistance, the higher the MTV, the better will be the response to chemotherapy.CONCLUSIONS:Quantitative assessment by MTV rather than by SUVmax and TLG on PET/CT may be helpful for stratifying patients who present with peritoneal carcinomatosis from EOC, in order to implement the appropriate therapeutic regimen.

BACKGROUND/OBJECTIVE:Advanced PD is often associated with cognitive impairment and frequent falls. We describe a suggestive case report of PD associated with mild cognitive impairment (MCI) and falls. The aim of our study was to test alteration in balance potentially related to use of acetylcholinesterase inhibitor (AchEI). We address this hypothesis after keeping the patient in stable dosage of dopamine agonist.METHODS/MEASUREMENTS:We describe an initial pharmacological management in a 78-year-old man affected by Parkinson disease (PD) associated with mild cognitive impairment (MCI) and history of falls. The diagnosis of PD was also confirmed by SPECT with DATSCAN, after CT-brain exclusion of potential other causes of the symptoms. Cognitive and motor performances of the patient were initially evaluated by Mini Mental Examination State Examination (MMSE), Short Physical Performance Battery (SPPB) and Romberg test. We also recorded gait parameters using an accelerometer, while balance and stability were assessed by stabilometric platform with open and closed eyes. We repeated cognitive and motor tests and gait and balance evaluation after stable dosage of dopamine agonist before and after introduction of AchEI.RESULTS:After starting dopamine agonist therapy, there was a significant improvement in gait parameters (speed, stride/min, stride length, swing duration, and decrease in gait cycle duration and rolling duration). When stable dosage of dopamine agonist was reached, AchEI was introduced obtaining not only a significant improvement of cognitive performance, but also a significant positive change in balance.CONCLUSION AND RELEVANCE:We hypothesize that AchEI could improve stability, balance and postural instability in addition to cognitive performance in PD with MCI and balance deficits.

Purpose : we evaluated the prognostic significance of standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on [F-18]FDG PET/CT in patients with non-surgical non-small-cell lung cancer (NSCLC). Material and Methods : 103 patients (mean age, 65,6±16 years) underwent [F-18]FDG PET/CT before the chemotherapy. The SUVmax value, the MTV (cm3; 42% threshold) and the TLG (g) were registered. The patients were followed up 18 months thereafter (range 12-55 months). Main events such as failure to respond without progression, progression and/or disease-related death constituted surrogate end-points. T he optimal SUVmax, MTV and TLG cut-off to predict the patientsu0027 outcome was estimated. PET/CT results were then related to disease outcome (progression free survival; PFS). Results: t he Kaplan-Meier survival analysis for SUVmax showed a significant better PFS in patients presenting lower values as compared to those having higher ( p u003c0.05, log-rank test ). MTV and TLG were not suitable for predicting PFS apart from the subset with mediastinal nodal involvement. Conclusions : despite the availability of new tools for the quantitative assessment of disease activity on PET/CT the SUVmax rather than MTV and TLG remains the only predictor for PFS in NSCLC patients. MTV holds a value only when concomitant nodal involvement occurs.

The complex cross-talk between tumor cells and their surrounding stromal environment plays a key role in the pathogenesis of cancer. Among several cell types that constitute the tumor stroma, bone marrow-derived mesenchymal stem cells (BM-MSCs) selectively migrate toward the tumor microenvironment and contribute to the active formation of tumor-associated stroma. Therefore, here we elucidate the involvement of BM-MSCs to promote osteosarcoma (OS) and hepatocellular carcinoma (HCC) cells migration and invasion and deepening the role of specific pathways. We analyzed the function of aquaporin 1 (AQP1), a water channel known to promote metastasis and neoangiogenes. AQP1 protein levels were analyzed in OS (U2OS) and HCC (SNU-398) cells exposed to conditioned medium from BM-MSCs. Tumor cell migration and invasion in response to BM-MSC conditioned medium were evaluated through a wound healing assay and Boyden chamber, respectively. The results showed that the AQP1 level was increased in both tumor cell lines after treatment with BM-MSC conditioned medium. Moreover, BM-MSCs-mediated tumor cell migration and invasion were hampered after treatment with AQP1 inhibitor. These data suggest that the recruitment of human BM-MSCs into the tumor microenvironment might cause OS and HCC cell migration and invasion through involvement of AQP1.