State-of-the-Art Hybrid Imaging of Neuroendocrine Neoplasms.

ABSTRACT: Neuroendocrine neoplasms (NENs) may be challenging to diagnose due to their small size and diverse anatomical locations. Hybrid imaging techniques, specifically positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI), represent the current state-of-the-art for evaluating NENs. The preferred radiopharmaceuticals for NEN PET imaging are gallium-68 (68Ga) DOTA-peptides, which target somatostatin receptors (SSTR) overexpressed on NEN cells. Clinical applications of [68Ga]Ga-DOTA-peptides PET/CT include diagnosis, staging, prognosis assessment, treatment selection, and response evaluation. Fluorodeoxyglucose-18 (18F-FDG) PET/CT aids in detecting low-SSTR-expressing lesions and helps in patient stratification and treatment planning, particularly in grade 3 neuroendocrine tumors (NETs). New radiopharmaceuticals such as fluorine-labeled SSTR agonists and SSTR antagonists are emerging as alternatives to 68Ga-labeled peptides, offering improved detection rates and favorable biodistribution. The maturing of PET/MRI brings advantages to NEN imaging, including simultaneous acquisition of PET and MRI images, superior soft tissue contrast resolution, and motion correction capabilities. The PET/MRI with [68Ga]Ga-DOTA-peptides has demonstrated higher lesion detection rates and more accurate lesion classification compared to PET/CT. Overall, hybrid imaging offers valuable insights in the diagnosis, staging, and treatment planning of NENs. Further research is needed to refine response assessment criteria and standardize reporting guidelines.

Simultaneous multislice diffusion-weighted imaging versus standard diffusion-weighted imaging in whole-body PET/MRI.

OBJECTIVE: To compare standard (STD-DWI) single-shot echo-planar imaging DWI and simultaneous multislice (SMS) DWI during whole-body positron emission tomography (PET)/MRI regarding acquisition time, image quality, and lesion detection. METHODS: Eighty-three adults (47 females, 57%), median age of 64 years (IQR 52-71), were prospectively enrolled from August 2018 to March 2020. Inclusion criteria were (a) abdominal or pelvic tumors and (b) PET/MRI referral from a clinician. Patients were excluded if whole-body acquisition of STD-DWI and SMS-DWI sequences was not completed. The evaluated sequences were axial STD-DWI at b-values 50-400-800 s/mm2 and the apparent diffusion coefficient (ADC), and axial SMS-DWI at b-values 50-300-800 s/mm2 and ADC, acquired with a 3-T PET/MRI scanner. Three radiologists rated each sequence's quality on a five-point scale. Lesion detection was quantified using the anatomic MRI sequences and PET as the reference standard. Regression models were constructed to quantify the association between all imaging outcomes/scores and sequence type. RESULTS: The median whole-body STD-DWI acquisition time was 14.8 min (IQR 14.1-16.0) versus 7.0 min (IQR 6.7-7.2) for whole-body SMS-DWI, p < 0.001. SMS-DWI image quality scores were higher than STD-DWI in the abdomen (OR 5.31, 95% CI 2.76-10.22, p < 0.001), but lower in the cervicothoracic junction (OR 0.21, 95% CI 0.10-0.43, p < 0.001). There was no significant difference in the chest, mediastinum, pelvis, and rectum. STD-DWI detected 276/352 (78%) lesions while SMS-DWI located 296/352 (84%, OR 1.46, 95% CI 1.02-2.07, p = 0.038). CONCLUSIONS: In cancer staging and restaging, SMS-DWI abbreviates acquisition while maintaining or improving the diagnostic yield in most anatomic regions. KEY POINTS: • Simultaneous multislice diffusion-weighted imaging enables faster whole-body image acquisition. • Simultaneous multislice diffusion-weighted imaging maintains or improves image quality when compared to single-shot echo-planar diffusion-weighted imaging in most anatomical regions. • Simultaneous multislice diffusion-weighted imaging leads to superior lesion detection.

2021 Top Images in Radiology: Radiology In Training Editors' Choices.

Online supplemental material is available for this article.

Ovarian cancer reporting lexicon for computed tomography (CT) and magnetic resonance (MR) imaging developed by the SAR Uterine and Ovarian Cancer Disease-Focused Panel and the ESUR Female Pelvic Imaging Working Group.

OBJECTIVES: Imaging evaluation is an essential part of treatment planning for patients with ovarian cancer. Variation in the terminology used for describing ovarian cancer on computed tomography (CT) and magnetic resonance (MR) imaging can lead to ambiguity and inconsistency in clinical radiology reports. The aim of this collaborative project between Society of Abdominal Radiology (SAR) Uterine and Ovarian Cancer (UOC) Disease-focused Panel (DFP) and the European Society of Uroradiology (ESUR) Female Pelvic Imaging (FPI) Working Group was to develop an ovarian cancer reporting lexicon for CT and MR imaging. METHODS: Twenty-one members of the SAR UOC DFP and ESUR FPI working group, one radiology clinical fellow, and two gynecologic oncology surgeons formed the Ovarian Cancer Reporting Lexicon Committee. Two attending radiologist members of the committee prepared a preliminary list of imaging terms that was sent as an online survey to 173 radiologists and gynecologic oncologic physicians, of whom 67 responded to the survey. The committee reviewed these responses to create a final consensus list of lexicon terms. RESULTS: An ovarian cancer reporting lexicon was created for CT and MR Imaging. This consensus-based lexicon has 6 major categories of terms: general, adnexal lesion-specific, peritoneal carcinomatosis-specific, lymph node-specific, metastatic disease -specific, and fluid-specific. CONCLUSIONS: This lexicon for CT and MR imaging evaluation of ovarian cancer patients has the capacity to improve the clarity and consistency of reporting disease sites seen on imaging. KEY POINTS: • This reporting lexicon for CT and MR imaging provides a list of consensus-based, standardized terms and definitions for reporting sites of ovarian cancer on imaging at initial diagnosis or follow-up. • Use of standardized terms and morphologic imaging descriptors can help improve interdisciplinary communication of disease extent and facilitate optimal patient management. • The radiologists should identify and communicate areas of disease, including difficult to resect or potentially unresectable disease that may limit the ability to achieve optimal resection.

Rare Mesenchymal Tumors of the Pelvis: Imaging and Pathologic Correlation.

Most pelvic tumors originate from the organs. Less commonly, tumors can arise from the various anatomic pelvic compartments and are comprised of mesenchymal tissue: muscles, connective tissue, vessels, lymphatics, and fat. Among some of the rarer entities are benign tumors (eg, angiomyxoma, cellular angiofibroma, and desmoid fibromatosis), malignant tumors (eg, sarcoma), and tumors that can manifest as benign or malignant (eg, solitary fibrous tumor or nerve sheath tumor). Because these tumors are uncommon and often manifest with nonspecific clinical features, imaging (usually MRI) is an initial step in the evaluation. Radiologists interpreting these images are asked to help narrow the differential diagnosis and assess the likelihood of malignancy for treatment planning. Thus, the MRI report should include the imaging features that would indicate the underlying tissue histology for pathologic diagnosis as well as a description of the anatomic extent and pattern of growth. The authors describe multiple locally aggressive benign and malignant mesenchymal tumors and highlight characteristic clinical and imaging features that enable the radiologist to narrow the differential diagnosis. The anatomic spaces of the pelvis are reviewed with illustrations to aid the radiologist in describing these tumors, which often span multiple pelvic compartments. Tumor appearance at T2-weighted, diffusion-weighted, and postcontrast MRI is summarized and illustrated with correlation at CT or fluorodeoxyglucose PET/CT, when available. MRI features that correspond to specific types of tissue (eg, myxoid, fibrous, or vascular) are highlighted and correlated with images from pathologic evaluation. Online supplemental material is available for this article. ©RSNA, 2021.

Update on MRI in Evaluation and Treatment of Endometrial Cancer.

Endometrial cancer is the second most common gynecologic cancer worldwide and the most common gynecologic cancer in the United States, with an increasing incidence in high-income countries. Although the International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer is a surgical staging system, contemporary published evidence-based data and expert opinions recommend MRI for treatment planning as it provides critical diagnostic information on tumor size and depth, extent of myometrial and cervical invasion, extrauterine extent, and lymph node status, all of which are essential in choosing the most appropriate therapy. Multiparametric MRI using a combination of T2-weighted sequences, diffusion-weighted imaging, and multiphase contrast-enhanced imaging is the mainstay for imaging assessment of endometrial cancer. Identification of important prognostic factors at MRI improves both treatment selection and posttreatment follow-up. MRI also plays a crucial role for fertility-preserving strategies and in patients who are not surgical candidates by helping guide therapy and identify procedural complications. This review is a product of the Society of Abdominal Radiology Uterine and Ovarian Cancer Disease-Focused Panel and reflects a multidisciplinary international collaborative effort to summarize updated information highlighting the role of MRI for endometrial cancer depiction and delineation, treatment planning, and follow-up. The article includes information regarding dedicated MRI protocols, tips for MRI reporting, imaging pitfalls, and strategies for image quality optimization. The roles of MRI-guided radiation therapy, hybrid PET/MRI, and advanced MRI techniques that are applicable to endometrial cancer imaging are also discussed. Online supplemental material is available for this article. ©RSNA, 2022.

Structure of mouse cytosolic sulfotransferase SULT2A8 provides insight into sulfonation of 7α-hydroxyl bile acids.

Cytosolic sulfotransferases (SULTs) catalyze the transfer of a sulfonate group from the cofactor 3'-phosphoadenosine 5'-phosphosulfate to a hydroxyl (OH) containing substrate and play a critical role in the homeostasis of endogenous compounds, including hormones, neurotransmitters, and bile acids. In human, SULT2A1 sulfonates the 3-OH of bile acids; however, bile acid metabolism in mouse is dependent on a 7α-OH sulfonating SULT2A8 via unknown molecular mechanisms. In this study, the crystal structure of SULT2A8 in complex with adenosine 3',5'-diphosphate and cholic acid was resolved at a resolution of 2.5 Å. Structural comparison with human SULT2A1 reveals different conformations of substrate binding loops. In addition, SULT2A8 possesses a unique substrate binding mode that positions the target 7α-OH of the bile acid close to the catalytic site. Furthermore, mapping of the critical residues by mutagenesis and enzyme activity assays further highlighted the importance of Lys44 and His48 for enzyme catalysis and Glu237 in loop 3 on substrate binding and stabilization. In addition, limited proteolysis and thermal shift assays suggested that the cofactor and substrates have protective roles in stabilizing SULT2A8 protein. Together, the findings unveil the structural basis of bile acid sulfonation targeting 7α-OH and shed light on the functional diversity of bile acid metabolism across species.

Improving staging of rectal cancer in the pelvis: the role of PET/MRI.

PURPOSE: The role of positron emission tomography/magnetic resonance (PET/MR) in evaluating the local extent of rectal cancer remains uncertain. This study aimed to investigate the possible role of PET/MR versus magnetic resonance (MR) in clinically staging rectal cancer. METHODS: This retrospective two-center cohort study of 62 patients with untreated rectal cancer investigated the possible role of baseline staging PET/MR versus stand-alone MR in determination of clinical stage. Two readers reviewed T and N stage, mesorectal fascia involvement, tumor length, distance from the anal verge, sphincter involvement, and extramural vascular invasion (EMVI). Sigmoidoscopy, digital rectal examination, and follow-up imaging, along with surgery when available, served as the reference standard. RESULTS: PET/MR outperformed MR in evaluating tumor size (42.5 ± 21.03 mm per the reference standard, 54 ± 20.45 mm by stand-alone MR, and 44 ± 20 mm by PET/MR, P = 0.004), and in identifying N status (correct by MR in 36/62 patients [58%] and by PET/MR in 49/62 cases [79%]; P = 0.02) and external sphincter infiltration (correct by MR in 6/10 and by PET/MR in 9/10; P = 0.003). No statistically significant differences were observed in relation to any other features. CONCLUSION: PET/MR provides a more precise assessment of the local extent of rectal cancers in evaluating cancer length, N status, and external sphincter involvement. PET/MR offers the opportunity to improve clinical decision-making, especially when evaluating low rectal tumors with possible external sphincter involvement.

Multisystem Assessment of the Imaging Manifestations of Coagulopathy in Hospitalized Patients With Coronavirus Disease (COVID-19).

BACKGROUND. Coronavirus disease (COVID-19) is known to be associated with a distinct form of coagulopathy. OBJECTIVE. The purpose of this study was to describe the imaging manifestations of COVID-19-associated coagulopathy across anatomic sites and modalities in hospitalized patients and to identify clinical variables associated with positive imaging findings. METHODS. We conducted a retrospective review of consecutive adult patients with COVID-19 admitted to our hospital over a 3-week period. Data on patient demographics, hematologic values, cross-sectional imaging examinations, and clinical outcomes (death and intubation) were collected. Imaging was reviewed for manifestations of coagulopathy. Multivariable logistic regression analyses were performed to assess associations of patient demographics, hematologic markers, and outcomes with the need for imaging and imaging manifestations of coagulopathy. RESULTS. Of 308 hospitalized patients with COVID-19, 142 (46%) underwent 332 cross-sectional imaging examinations. Of these, 37 (26%) had imaging results positive for coagulopathy. The most common imaging manifestations of coagulopathy were pulmonary embolus (n = 21) on contrast-enhanced CT or CTA, thrombus in the upper- or lower-extremity veins (n = 13) on Doppler ultrasound, end-organ infarction in the bowel (n = 4) and kidney (n = 4) on contrast-enhanced CT, and thrombus or parenchymal infarction in the brain (n = 2) on contrast-enhanced CTA or MRI with MRA. Among patients with imaging results positive for coagulopathy, eight (22%) had multisite involvement. Thrombi were multifocal in four of five patients with positive upper-extremity and three of eight patients with positive lower-extremity examination results and involved superficial veins, deep veins, or both. In multivariable analysis, intubation (p < .001) and prolonged prothrombin time (p = .04) were significantly associated with undergoing imaging. No patient variable was significantly associated with imaging results positive for coagulopathy (p > .05). CONCLUSION. Imaging commonly shows manifestations of coagulopathy in hospitalized patients with COVID-19. Over one-fifth of patients with such manifestations show multisite involvement. Clinical variables poorly predict which patients have positive imaging results, indicating a complementary role of imaging in detecting COVID-19-associated coagulopathy. CLINICAL IMPACT. In patients with COVID-19 with suspected systemic coagulopathy, pulmonary CTA, extremity Doppler ultrasound, contrast-enhanced abdominal CT, and contrast-enhanced brain MRI and MRA may all be appropriate in the absence of imaging contraindications.

Abdominal Imaging Findings in COVID-19: Preliminary Observations.

Background Angiotensin-converting enzyme 2, a target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrates its highest surface expression in the lung, small bowel, and vasculature, suggesting abdominal viscera may be susceptible to injury. Purpose To report abdominal imaging findings in patients with coronavirus disease 2019. Materials and Methods In this retrospective cross-sectional study, patients consecutively admitted to a single quaternary care center from March 27 to April 10, 2020, who tested positive for SARS-CoV-2 were included. Abdominal imaging studies performed in these patients were reviewed, and salient findings were recorded. Medical records were reviewed for clinical data. Univariable analysis and logistic regression were performed. Results A total of 412 patients (average age, 57 years; range, 18 to >90 years; 241 men, 171 women) were evaluated. A total of 224 abdominal imaging studies were performed (radiography, n = 137; US, n = 44; CT, n = 42; MRI, n = 1) in 134 patients (33%). Abdominal imaging was associated with age (odds ratio [OR], 1.03 per year of increase; P = .001) and intensive care unit (ICU) admission (OR, 17.3; P < .001). Bowel-wall abnormalities were seen on 31% of CT images (13 of 42) and were associated with ICU admission (OR, 15.5; P = .01). Bowel findings included pneumatosis or portal venous gas, seen on 20% of CT images obtained in patients in the ICU (four of 20). Surgical correlation (n = 4) revealed unusual yellow discoloration of the bowel (n = 3) and bowel infarction (n = 2). Pathologic findings revealed ischemic enteritis with patchy necrosis and fibrin thrombi in arterioles (n = 2). Right upper quadrant US examinations were mostly performed because of liver laboratory findings (87%, 32 of 37), and 54% (20 of 37) revealed a dilated sludge-filled gallbladder, suggestive of bile stasis. Patients with a cholecystostomy tube placed (n = 4) had negative bacterial cultures. Conclusion Bowel abnormalities and gallbladder bile stasis were common findings on abdominal images of patients with coronavirus disease 2019. Patients who underwent laparotomy often had ischemia, possibly due to small-vessel thrombosis. © RSNA, 2020.

Male-biased fasting-induced changes in hepatic tauro-cholic acid and plasma cholesterol in Sult2a8-haplodeficient mice.

SULT2A8 is a male-predominant and liver-specific mouse cytosolic sulfotransferase (SULT) that sulfonates 7α-hydroxyl (7α-OH) bile acids in vitro. Sulfonation regulates bile acid homeostasis, which in turn regulates cholesterol and energy metabolism. Using the Sult2a8-heterozygous (HT) mouse model created earlier in our laboratory, we aimed to investigate the physiological role of SULT2A8 in sulfonating 7α-OH bile acids and its impact on energy metabolism in vivo under both fed and energy-deprivation conditions. Disruption of one allele of the Sult2a8 gene in male HT mice resulted in losing ~ 50% of the 7α-OH sulfonating activity compared to wild-type (WT) control, but no significant change in female HT mice. Under the fed condition comparing the levels of hepatic and biliary bile acids as well as plasma/serum energy metabolites, HT mice displayed a profile similar to that of WT mice, suggesting that the Sult2a8-haplodeficient mice conducted normal energy metabolism. However, after 48-h fasting, a significant decrease in plasma cholesterol level was found in male HT mice but without any significant reduction in female HT mice. Of interest, in male Sult2a8-haplodeficient mice, an increase of the hepatic taurine-conjugated cholic acid level was noted but no noticeable change in other tested bile acids after fasting. Taken together, SULT2A8 is a male-specific and key hepatic SULT in metabolizing 7α-OH primary bile acids. During energy deprivation, SULT2A8 is required to maintain the bile acid and cholesterol metabolism, suggesting SULT is a potential therapeutic target for controlling metabolic diseases.

2018 FIGO Staging System for Uterine Cervical Cancer: Enter Cross-sectional Imaging.

Imaging plays a central role in the 2018 International Federation of Gynecology and Obstetrics staging system for uterine cervical cancer. The revision calls for a more precise measurement of primary tumor size, best assessed with imaging. Evaluation for abdominopelvic retroperitoneal lymphadenopathy, either with imaging alone or with pathologic analysis, is now also part of staging. Choice of modality depends on the technology available within the practice setting. In high-resource settings, pelvic MRI (to assess tumor size and central pelvic spread) and torso fluorodeoxyglucose PET/CT (to assess lymphadenopathy and distant metastases) are used to assign stage and to plan therapy. In lower-resource settings, analogous modalities are pelvic US and chest radiography. Although imaging is already a part of pretreatment planning in some high-resource settings, its incorporation into assigning stage is a new development.

CT prediction of surgical outcome in patients with advanced epithelial ovarian carcinoma undergoing neoadjuvant chemotherapy.

OBJECTIVE: A scoring system has been proposed to predict gross residual disease at primary debulking surgery (PDS) for advanced epithelial ovarian cancer. This scoring system has not been assessed in patients undergoing neoadjuvant chemotherapy (NACT). The aim of this study is to assess the reproducibility and prognostic significance of the scoring system when applied to women undergoing NACT followed by interval debulking surgery (IDS). METHODS: A retrospective cohort study was conducted of patients with advanced ovarian cancer who underwent NACT and IDS between 2005 and 2014. Change in tumor burden using computed tomography (CT) at diagnosis (T0) and after initiation of NACT but before IDS (T1) was independently assessed by two radiologists blinded to outcomes using two read criteria: a scoring system utilizing clinical and radiologic criteria and RECIST 1.1. Relationship between CT assessments to surgical outcome, progression free survival (PFS) and overall survival (OS) were evaluated. Reader agreement was measured using Fleiss's kappa (ĸ). RESULTS: 76 patients were analyzed. Optimal surgical outcome was achieved in 69 (91%) of patients. Median progression free survival was 13.2 months and overall survival was 32.6 months, respectively. Predictive score change from T0 to T1 of >1 (denoting an improvement in disease burden) was associated with optimal cytoreduction (p = 0.02 and 0.01 for readers 1 and 2, respectively). Neither predictive score nor RECIST 1.1 assessment was predictive of OS or PFS. Reader agreement was substantial for predictive score (κ = 0.77) and moderate for RECIST (κ = 0.51) assessments. CONCLUSIONS: A change in score before and after neoadjuvant chemotherapy minimizes reader variability and predicts surgical outcome.

Identification of Distant Metastatic Disease in Uterine Cervical and Endometrial Cancers with FDG PET/CT: Analysis from the ACRIN 6671/GOG 0233 Multicenter Trial.

Purpose To assess the accuracy of staging positron emission tomography (PET)/computed tomography (CT) in detecting distant metastasis in patients with local-regionally advanced cervical and high-risk endometrial cancer in the clinical trial by the American College of Radiology Imaging Network (ACRIN) and the Gynecology Oncology Group (GOG) (ACRIN 6671/GOG 0233) and to compare central and institutional reader performance. Materials and Methods In this prospective multicenter trial, PET/CT and clinical data were reviewed for patients enrolled in ACRIN 6671/GOG 0233. Two central readers, blinded to site read and reference standard, reviewed PET/CT images for distant metastasis. Central review was then compared with institutional point-of-care interpretation. Reference standard was pathologic and imaging follow-up. Test performance for central and site reviews of PET/CT images was calculated and receiver operating characteristic analysis was performed. Generalized estimating equations and nonparametric bootstrap procedure for clustered data were used to assess statistical significance. Results There were 153 patients with cervical cancer and 203 patients with endometrial cancer enrolled at 28 sites. Overall prevalence of distant metastasis was 13.7% (21 of 153) for cervical cancer and 11.8% (24 of 203) for endometrial cancer. Central reader PET/CT interpretation demonstrated sensitivity, specificity, positive predictive value (PPV), and negative predictive value of 54.8%, 97.7%, 79.3%, and 93.1% for cervical cancer metastasis versus 64.6%, 98.6%, 86.1%, and 95.4% for endometrial cancer, respectively. By comparison, local institutional review demonstrated sensitivity, specificity, PPV, and negative predictive value of 47.6%, 93.9%, 55.6%, and 91.9% for cervical cancer metastasis and 66.7%, 93.9%, 59.3%, and 95.5% for endometrial cancer, respectively. For central readers, the specificity and PPV of PET/CT detection of cervical and endometrial cancer metastases were all significantly higher compared with that of local institutional review (P < .05). Central reader area under the receiver operating characteristic curve (AUC) values were 0.78 and 0.89 for cervical and endometrial cancer, respectively; these were not significantly different from local institutional AUC values (0.75 and 0.84, respectively; P > .05 for both). Conclusion FDG PET/CT demonstrates high specificity and PPV for detecting distant metastasis in cervical and endometrial cancer and should be included in the staging evaluation. Blinded central review of imaging provides improved specificity and PPV for the detection of metastases and should be considered for future oncologic imaging clinical trials. © RSNA, 2017.

Molecular and functional characterization of tumor-induced factor (TIF): Hamster homolog of CXCL3 (GROγ) displays tumor suppressive activity.

Previously our lab has created a mouse ovarian xenograft model of copy number variation (CNV)-mediated G protein-coupled receptor (GPCR) MAS-driven tumorigenesis, and RNA profiling identified a putative chemokine tumor-induced factor (Tif). Sequence analysis and chemotactic study suggested that Tif was likely to be a hamster homolog of human GROγ (CXCL3) [IJC 125 (2009): 1316-1327]. In the present study, we report the molecular and functional characterization of the Tif gene. Genomic study of CHO-K1 cells indicated that Tif gene consisted of 4 exons, characterized with an antisense B1 element which is embedded in the fourth exon. Two Tif transcripts were identified which shared identical sequences except that a string of 71-nt derived from the antisense B1 element was deficient in the shorter transcript. Of interests, B1-like RNA ladder was detected in xenografts. Functional studies showed that TIF induced chemotaxis and neovessel formation. Pharmacological studies suggested that TIF activated Gi-coupled CXCR2 and induced both calcium mobilization and ERK1/2 phosphorylation, and suppressed forskolin-stimulated cAMP accumulation. In addition, secreted matured TIF functioned as an autocrine factor and promoted anchorage-independent growth. Unexpectedly, TIF delayed the onset of tumor formation, possibly via suppressing proliferation of stromal fibroblasts. However, TIF did not exert any inhibitory effect on tumor growth. Potentially, TIF could be used for preventing cancer relapse.