Curcumin Suppresses Colon Cancer In Vitro and In Vivo

Objective: To discuss In Vitro and In Vivo the effects of curcumin on colon cancer. Material and Methods: SW620 cell and nude mice with tumor were respectively divided into 3 groups: NC, low, middle, high and 5-Fu groups. Measuring the cell activity by MTT, the cell cycle and cell apoptosis using flow cytometry and relative proteins by WB assay in cell experiment. Evaluating tumor volume and weight, cell apoptosis rate by TUNEL assay and relative proteins by Immunohistochemistry (IHC). Results: Compared with NC group, the SW620 cell activity was significantly depressed with cell apoptosis and G1 phase rates increasing and PI3K, AKT and P53 proteins expression were significantly differences in curcumin treated groups with dose-dependent by WB assay; In Vivo study, the tumor volume and size were significantly suppressed and positive cell number were significantly up-regulation in curcumin treated groups with dose-dependent, and PI3K, AKT and P53 proteins expression were significantly differences in curcumin treated groups with dose-dependent by IHC. Conclusions: Curcumin had anti-tumor effects to colon cancer via regulation PI3K/AKT/P53 pathway In Vivo and vitro study.

miR-12 Derived from Bone Marrow Mesenchymal Stem Cells Accelerates the Development of Human Papillomavirus by Up-Regulating AN1

The miRNA derived from Bone marrow mesenchymal stem cells (BMSCs) have crucial effects on tumors. The tumor could be affected by the abnormal expression of miRNA in human papillomavirus (HPV). Our study aimed to identify the potential brand-new biomarker in order to reveal the pathogenesis of HPV. miRNA derived from BMSCs was detected and identified. The action of miR-12 on biological behavior of HPV was detected. The level of AN1 protein was detected by Western-blot and IHC method. The relationship between miR-12 and AN1 was assessed by bioinformatics analysis and luciferase assay. The tumor cell biological behaviors were evaluated by manipulating miR12 and AN1 level. The tumor volume derived from BMSCs was diminished significantly compared with normal tissues. The tumor volume was bigger after combined injection with Hela cell and miR-12 compared with single injection. The cell proliferative and invasive ability was strengthened after transfection with miR-12mimics. The cell invasive ability was reduced significantly after transfection of si-miR-12. AN1 was a target gene of miR-12 as confirmed by the analysis on bioinformatics and luciferase activity. The phenotype was reversed after the silent presentation of AN1 was disturbed. In conclusion, miR-12 expression is elevated in HPV cells and affects HPV cells through targeting the AN1 signaling pathway.

Automatic segmentation of head and neck primary tumors on MRI using a multi-view CNN

Background Accurate segmentation of head and neck squamous cell cancer (HNSCC) is important for radiotherapy treatment planning. Manual segmentation of these tumors is time-consuming and vulnerable to inconsistencies between experts, especially in the complex head and neck region. The aim of this study is to introduce and evaluate an automatic segmentation pipeline for HNSCC using a multi-view CNN (MV-CNN). Methods The dataset included 220 patients with primary HNSCC and availability of T1-weighted, STIR and optionally contrast-enhanced T1-weighted MR images together with a manual reference segmentation of the primary tumor by an expert. A T1-weighted standard space of the head and neck region was created to register all MRI sequences to. An MV-CNN was trained with these three MRI sequences and evaluated in terms of volumetric and spatial performance in a cross-validation by measuring intra-class correlation (ICC) and dice similarity score (DSC), respectively. Results The average manual segmented primary tumor volume was 11.8±6.70 cm3 with a median [IQR] of 13.9 [3.22-15.9] cm3. The tumor volume measured by MV-CNN was 22.8±21.1 cm3 with a median [IQR] of 16.0 [8.24-31.1] cm3. Compared to the manual segmentations, the MV-CNN scored an average ICC of 0.64±0.06 and a DSC of 0.49±0.19. Improved segmentation performance was observed with increasing primary tumor volume: the smallest tumor volume group (<3 cm3) scored a DSC of 0.26±0.16 and the largest group (>15 cm3) a DSC of 0.63±0.11 (p<0.001). The automated segmentation tended to overestimate compared to the manual reference, both around the actual primary tumor and in false positively classified healthy structures and pathologically enlarged lymph nodes. Conclusion An automatic segmentation pipeline was evaluated for primary HNSCC on MRI. The MV-CNN produced reasonable segmentation results, especially on large tumors, but overestimation decreased overall performance. In further research, the focus should be on decreasing false positives and make it valuable in treatment planning.

PET metabolic tumor volume as a new prognostic factor in childhood rhabdomyosarcoma

Purpose Childhood RMS is a rare malignant disease in which evaluation of tumour spread at diagnosis is essential for therapeutic management. F-18 FDG-PET imaging is currently used for initial RMS disease staging. Materials and methods This multicentre retrospective study in six French university hospitals was designed to analyse the prognostic accuracy of MTV at diagnosis for patients with RMS between 1 January 2007 and 31 October 2017, for overall (OS) and progression-free survival (PFS). MTV was defined as the sum of the primitive tumour and the largest metastasis, where relevant, with a 40% threshold of the primary tumour SUVmax. Additional aims were to define the prognostic value of SUVmax, SUVpeak, and bone lysis at diagnosis. Results Participants were 101 patients with a median age of 7.4 years (IQR [4.0-12.5], 62 boys), with localized disease (35 cases), regional nodal spread (43 cases), or distant metastases (23). 44 patients had alveolar subtypes. In a univariate analysis, a MTV greater than 200 cm3 was associated with OS (HR = 3.47 [1.79;6.74], p<0.001) and PFS (HR = 3.03 [1.51;6.07], p = 0.002). SUVmax, SUVpeak, and bone lysis also influenced OS (respectively p = 0.005, p = 0.004 and p = 0.007) and PFS (p = 0.029, p = 0.019 and p = 0.015). In a multivariate analysis, a MTV greater than 200 cm3 was associated with OS (HR = 2.642 [1.272;5.486], p = 0.009) and PFS (HR = 2.707 [1.322;5.547], p = 0.006) after adjustment for confounding factors, including SUVmax, SUVpeak, and bone lysis. Conclusion A metabolic tumor volume greater than 200 cm3, SUVmax, SUVpeak, and bone lysis in the pre-treatment assessment were unfavourable for outcome.

Regression Analysis of Rectal Cancer and Possible Application of Artificial Intelligence (AI) Utilization in Radiotherapy

Artificial Intelligence (AI) has been widely employed in the medical field in recent years in such areas as image segmentation, medical image registration, and computer-aided detection. This study explores one application of using AI in adaptive radiation therapy treatment planning by predicting the tumor volume reduction rate (TVRR). Cone beam computed tomography (CBCT) scans of twenty rectal cancer patients were collected to observe the change in tumor volume over the course of a standard five-week radiotherapy treatment. In addition to treatment volume, patient data including patient age, gender, weight, number of treatment fractions, and dose per fraction were also collected. Application of a stepwise regression model showed that age, dose per fraction and weight were the best predictors for tumor volume reduction rate.

Limited Adenocarcinoma of the Prostate on Needle Core Biopsy

Context.— Grading small foci of prostate cancer on a needle biopsy is often difficult, yet the clinical significance of accurate grading remains uncertain. Objective.— To assess if grading of limited adenocarcinoma on prostate biopsy specimen is critical. Design.— We studied 295 consecutive patients undergoing extended-sextant biopsy with only 1-core involvement of adenocarcinoma, followed by radical prostatectomy. Results.— The linear tumor lengths on these biopsy specimens were: less than 1 mm (n = 114); 1 mm or more or less than 2 mm (n = 82); 2 mm or more or less than 3 mm (n = 35); and 3 mm or more (n = 64). Longer length was strongly associated with higher Grade Group (GG) on biopsy or prostatectomy specimen, higher risk of extraprostatic extension/seminal vesicle invasion and positive surgical margin, and larger estimated tumor volume. When cases were compared based on biopsy specimen GG, higher grade was strongly associated with higher prostatectomy specimen GG, higher incidence of pT3/pT3b disease, and larger tumor volume. Outcome analysis further showed significantly higher risks for biochemical recurrence after radical prostatectomy in patients with 1 mm or more, 2 mm or more, 3 mm or more, GG2-4, GG3-4, GG4, less than 1 mm/GG2-4, less than 1 mm/GG3-4, less than 2 mm/GG3-4, 3 mm or more/GG2-4, or 3 mm or more/GG3-4 tumor on biopsy specimens, compared with respective control subgroups. In particular, 3 mm or more, GG3, and GG4 on biopsy specimens showed significance as independent prognosticators by multivariate analysis. Meanwhile, there were no significant differences in the rate of upgrading or downgrading after radical prostatectomy among those subgrouped by biopsy specimen tumor length (eg, &lt;1 mm [44.7%] versus ≥1/&lt;2 mm [41.5%] versus ≥2/&lt;3 mm [45.7%] versus ≥3 mm [46.9%]). Conclusions.— These results indicate that pathologists still need to make maximum efforts to grade relatively small prostate cancer on biopsy specimens.

The Clinical Significance of Perineural Invasion by Prostate Cancer on Needle Core Biopsy

Context.— Perineural invasion (PNI) by prostate cancer has been associated with adverse pathology, including extraprostatic extension. However, the significance of PNI quantification on prostate biopsy (PBx) remains unclear. Objective.— To compare radical prostatectomy (RP) findings and long-term outcomes in patients whose PBx had exhibited PNI. Design.— We assessed 497 consecutive patients undergoing sextant (6-site/≥12-core) PBx showing conventional adenocarcinoma followed by RP. Results.— PNI was found in 1 (n = 290)/2 (n = 132)/3 (n = 47)/4 (n = 19)/5 (n = 5)/6 (n = 4) of the sites/regions of PBx. Compared with a single PNI site, multiple PNIs were significantly associated with higher preoperative prostate-specific antigen, higher Grade Group (GG) on PBx or RP, higher pT or pN category, positive surgical margin, and larger estimated tumor volume. When compared in subgroups of patients based on PBx GG, significant differences in RP GG (GG1–3), pT (GG1–2/GG1–3/GG2/GG3), surgical margin status (GG1–3/GG3/GG5), or tumor volume (GG1–2/GG1–3/GG2/GG3) between 1 versus multiple PNIs were observed. Moreover, there were significant differences in prostate-specific antigen (PNI sites: 1–2 versus 3–6/1–3 versus 4–6/1–4 versus 5–6), RP GG (1–3 versus 4–6/1–4 versus 5–6), pT (1–2 versus 3–6/1–3 versus 4–6), pN (1–3 versus 4–6), or tumor volume (1–2 versus 3–6/1–4 versus 5–6). Outcome analysis revealed significantly higher risks of disease progression in the entire cohort or PBx GG1–2/GG1–3/GG2/GG3/GG5 cases showing 2 to 6 PNIs, compared with respective controls with 1-site PNI. In multivariate analysis, multisite PNI was an independent predictor for progression (hazard ratio = 1.556, P = .03). Conclusions.— Multiple sites of PNI on PBx were associated with worse histopathologic features in RP specimens and poorer prognosis. PNI may thus need to be specified, if present, in every sextant site on PBx, especially those showing GG1–3 cancer.

Volume of Disease as a Predictor for Clinical Outcomes in Patients With Melanoma Brain Metastases Treated With Stereotactic Radiosurgery and Immune Checkpoint Therapy

Purpose/ObjectivesClinical trials of anti-Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein (CTLA-4) therapies have demonstrated a clinical benefit with low rates of neurologic adverse events in patients with melanoma brain metastases (MBMs). While the combined effect of these immunotherapies (ITs) and stereotactic radiosurgery (SRS) has yielded impressive results with regard to local control (LC) and overall survival (OS), it has also been associated with increased rates of radiation necrosis (RN) compared to historical series of SRS alone. We retrospectively reviewed patients treated with IT in combination with SRS to report on predictors of clinical outcomes.Materials and MethodsPatients were included if they had MBMs treated with SRS within 1 year of receiving anti-PD-1 and/or CTLA-4 therapy. Clinical outcomes including OS, LC, intracranial death (ID), and RN were correlated with type and timing of IT with SRS, radiation dose, total volume, and size and number of lesions treated.ResultsTwenty-nine patients with 171 MBMs were treated between May 2012 and May 2018. Patients had a median of 5 lesions treated (median volume of 6.5 cm3) over a median of 2 courses of SRS. The median dose was 21 Gy. Most patients were treated with ipilimumab (n = 13) or nivolumab-ipilimumab (n = 10). Most patients underwent SRS concurrently or within 3 months of receiving immunotherapy (n = 21). Two-year OS and LC were 54.4% and 85.5%, respectively. In addition, 14% of patients developed RN; however, only 4.7% of the total treated lesions developed RN. The median time to development of RN was 9.5 months. Patients with an aggregate tumor volume &gt;6.5 cm3 were found to be at increased risk of ID (p = 0.05) and RN (p = 0.03). There was no difference in OS, ID, or RN with regard to type of IT, timing of SRS and IT, number of SRS courses, SRS dose, or number of cumulative lesions treated.ConclusionsIn our series, patients treated with SRS and IT for MBMs had excellent rates of OS and LC; however, patients with an aggregate tumor volume &gt;6.5 cm3 were found to be at increased risk of ID and RN. Given the efficacy of combined anti-PD-1/CTLA-4 therapy for MBM management, further study of optimal selection criteria for the addition of SRS is warranted.

Effect of Neoadjuvant Iodine-125 Brachytherapy Upon Resection of Glioma

Background: A more extensive surgical resection of glioma contributes to improved overall survival (OS) and progression-free survival (PFS). However, some of the patients lost the chance of surgical resection when the tumor involves critical structures. Purpose: The present study aimed to assess the feasibility of neoadjuvant 125I brachytherapy followed by total gross resection for initially inoperable glioma.Methods:Six patients diagnosed with inoperable glioma due to invasion of eloquent areas, bi-hemispheric diffusion, or large tumor volume received 125I brachytherapy. Surgical resection was performed when the tumor shrank, allowing a safe resection, assessed by the neurosurgeons. Patients were followed up after surgery.Results:Tumor shrinkage after adjuvant 125I brachytherapy enabled a total gross resection of all six patients. Four patients were still alive at the last follow-up, with the longest survival time of more than 50 months, two of which returned to a normal life with the KPS of 100. Another two patients got a neurological injury with the KPS of 80 and 50, respectively. One patient with grade Ⅱ glioma died 34 months, and another patient with grade Ⅳ glioma died 40 months later after the combined therapy.Conclusions: In the present study, the results demonstrated that 125I brachytherapy enabled a complete resection of patients with initially unresectable gliomas. 125I brachytherapy may offer a proper neoadjuvant therapy method for glioma.