Anus preservation in low rectal adenocarcinoma based on MMR/MSI status (APRAM): a study protocol for a randomised, controlled, open-label, multicentre phase III trial.

BACKGROUND: Anus preservation has been a challenge in the treatment of patients with low rectal adenocarcinoma (within 5 cm from the anal verge) because it is difficult to spare the anus with its functioning sphincter complex under the safe margin of tumour resection. Patients with dMMR/MSI-H can achieve a favourable complete response (CR) rate by using a single immune checkpoint inhibitor. For patients with pMMR/MSS/MSI-L, intensified neoadjuvant three-drug chemotherapy may be the preferred option for anal preservation. In addition, the watch and wait (W&W) strategy has been proven safe and feasible for patients with rectal cancer who achieve a clinical complete response (cCR). Therefore, we initiated this clinical trial to explore the optimal neoadjuvant treatment pattern for patients with low locally advanced rectal cancer (LARC) with different MMR/MSI statuses, aiming to achieve a higher cCR rate with the W&W strategy and ultimately provide more patients with a chance of anus preservation. METHODS: This is a randomised, controlled, open-label, multicentre phase III trial. Patients with clinical stage T2-4 and/or N + tumours located within 5 cm from the anal verge are considered eligible. Based on the results of pathological biopsy, the patients are divided into two groups: dMMR/MSI-H and pMMR/MSS. Patients in the dMMR/MSI-H group will be randomly allocated in a 1:1 ratio to either arm A (monoimmunotherapy) or arm B (short-course radiotherapy followed by monoimmunotherapy). Patients in the pMMR/MSS group will be initially treated with long-term pelvic radiation with concurrent capecitabine combined with irinotecan. Two weeks after the completion of chemoradiotherapy (CRT), the patients will be randomly allocated in a 1:1 ratio to arm C (XELIRI six cycle regime) or arm D (FOLFIRINOX nine cycle regime). The irinotecan dose will be adjusted according to the UGT1A1-genotype. After treatment, a comprehensive assessment will be performed to determine whether a cCR has been achieved. If achieved, the W&W strategy will be adopted; otherwise, total mesorectal excision (TME) will be performed. The primary endpoint is cCR with the maintenance of 12 months at least, determined using digital rectal examination, endoscopy, and rectal MRI or PET/CT as a supplementary method. DISCUSSION: APRAM will explore the best anus preservation model for low LARC, combining the strategies of consolidation chemotherapy, immunotherapy, and short-course radiotherapy, and aims to preserve the anus of more patients using W&W. Our study provides an accurate individual treatment mode based on the MMR/MSI status for patients with low LARC, and more patients will receive the opportunity for anus preservation under our therapeutic strategy, which would transform into long-term benefits. TRIAL REGISTRATION: Clinicaltrials.gov NCT05669092 (Registered 28th Nov 2022).

Lipid metabolism and antioxidant system contribute to salinity tolerance in halophytic grass seashore paspalum in a tissue-specific manner.

Soil salinization is a growing issue that limits agriculture globally. Understanding the mechanism underlying salt tolerance in halophytic grasses can provide new insights into engineering plant salinity tolerance in glycophytic plants. Seashore paspalum (Paspalum vaginatum Sw.) is a halophytic turfgrass and genomic model system for salt tolerance research in cereals and other grasses. However, the salt tolerance mechanism of this grass largely unknown. To explore the correlation between Na+ accumulation and salt tolerance in different tissues, we utilized two P. vaginatum accessions that exhibit contrasting tolerance to salinity. To accomplish this, we employed various analytical techniques including ICP-MS-based ion analysis, lipidomic profiling analysis, enzyme assays, and integrated transcriptomic and metabolomic analysis. Under high salinity, salt-tolerant P. vaginatum plants exhibited better growth and Na+ uptake compared to salt-sensitive plants. Salt-tolerant plants accumulated heightened Na+ accumulation in their roots, leading to increased production of root-sourced H2O2, which in turn activated the antioxidant systems. In salt-tolerant plants, metabolome profiling revealed tissue-specific metabolic changes, with increased amino acids, phenolic acids, and polyols in roots, and increased amino acids, flavonoids, and alkaloids in leaves. High salinity induced lipidome adaptation in roots, enhancing lipid metabolism in salt-tolerant plants. Moreover, through integrated analysis, the importance of amino acid metabolism in conferring salt tolerance was highlighted. This study significantly enhances our current understanding of salt-tolerant mechanisms in halophyte grass, thereby offering valuable insights for breeding and genetically engineering salt tolerance in glycophytic plants.

Ultra-precise surface processing of LYSO scintillator crystals for Positron Emission Tomography.

The Lutetium-Yttrium Oxyorthosilicate (LYSO) is one of the most widely used scintillation crystal in the high-performance Positron Emission Tomography (PET) systems. The quality of the surface finish of the LYSO has an important impact on the light output, the decoding performance, the energy resolution and timing resolution of the PET detectors and systems. In this paper, we present an ultra-precise method for processing the surface of LYSO crystals. The hardness and elastic modulus of the crystals were initially measured using Nano indentation technology. The scintillators were fixed onto the plate in sparse, serried and continuous arrangements and polished using an alumina (Al2O3) and cerium oxide (CeO2) polishing solution with particles of varying size. We used a magnetorheological-polishing technique to polish the LYSO crystals. The polishing solution here included hydroxyl iron powder and hard abrasives. The hardness and elastic modulus of the crystals in question was, respectively, 11.18 ± 0.50 and 155.78 ± 4gigapascals (GPa). A 3D optical surface profiler (3D-OPS) and an atomic force microscope (AFM) were used to evaluate the quality of the polished surfaces. The average roughness of Ra 0.55 nm measured by 3D-OPS was achieved using a precise plate grinding and polishing technique. The magnetorheological-polishing method also obtained an excellent roughness of Ra 0.75 nm (3D-OPS). Our report of the use of these processing technologies can serve as a foundation for further in-depth research regarding the optimal techniques for scintillator surface processing.

MiR-200c inhibits autophagy and enhances radiosensitivity in breast cancer cells by targeting UBQLN1.

Radioresistance is a major challenge during the treatment of breast cancer. A further understanding of the mechanisms of radioresistance could provide strategies to address this challenge. In our study, we compared the expression of miR-200c in four distinct breast cancer cell lines: two representative basal cancer cells (MDA-MB-231 and BT549) vs. two representative luminal cancer cells (MCF-7 and BT474). The results revealed practically lower expression of miR-200c in the two basal cancer cell lines and higher expression of miR-200c in luminal cancer cells compared to the normal breast epithelial cell line MCF-10A. Ectopic expression of miR-200c in MDA-MB-231 cells inhibited irradiation-induced autophagy and sensitized the breast cancer cells to irradiation. We also identified UBQLN1 as a direct functional target of miR-200c involved in irradiation-induced autophagy and radioresistance. In 35 human breast cancer tissue samples, we detected an inverse correlation between the expression of miR-200c vs. UBQLN1 and LC3. These results indicate that the identified miR-200c/UBQLN1-mediated autophagy pathway may help to elucidate radioresistance in human breast cancer and might represent a therapeutic strategy.

MET inhibitor PHA-665752 suppresses the hepatocyte growth factor-induced cell proliferation and radioresistance in nasopharyngeal carcinoma cells.

Although ionizing radiation (IR) has provided considerable improvements in nasopharyngeal carcinoma (NPC), in subsets of patients, radioresistance is still a major problem in the treatment. In this study, we demonstrated that irradiation induced MET overexpression and activation, and the aberrant MET signal mediated by hepatocyte growth factor (HGF) induced radioresistance. We also found that MET inhibitor PHA-665752 effectively suppressed HGF induced cell proliferation and radioresistance in NPC cells. Further investigation indicated that PHA-665752 suppressed the phosphorylation of the Akt, ERK1/2, and STAT3 proteins in a dose-dependent manner. Our data indicated that the combination of IR with a MET inhibitor, such as PHA-665752, might be a promising therapeutic strategy for NPC.

MiR-451 increases radiosensitivity of nasopharyngeal carcinoma cells by targeting ras-related protein 14 (RAB14).

Radioresistance severely impedes the treatment of nasopharyngeal carcinoma (NPC). Recent evidence has shown that the abnormal expression of microRNAs (miRNAs) contributes to radiosensitivity. The aim of this study, therefore, was to investigate whether expression of the miRNAs correlated with radiosensitivity in the context of NPC. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to quantify miR-451 expression in two representative NPC cell lines. The role of miR-451 in NPC radiosensitivity was analyzed using a colony formation assay and an immunofluorescence assay with overexpression of miR-451 in NPC cells. Luciferase reporter assays, RT-PCR, and Western blot were performed to confirm the target of miR-451. High levels of miR-451 expression enhanced radiosensitivity in NPC cells by inhibiting the repair of irradiation-induced double-strand breaks (DSBs) and increasing apoptosis. The results also demonstrated that miR-451 directly targeted ras-related protein 14 (RAB14). Downregulation of RAB14 partially replicated the miR-451-mediated DSBs induced by ionizing radiation (IR). MiR-451 could be a potential target for enhancing radiosensitivity of NPC cells by targeting RAB14.

The status of p53 in cancer cells affects the role of autophagy in tumor radiosensitisation.

The function of autophagy in cancer has been intensively studied as a possible therapeutic target due to its unique ability to influence the cancer cells' resistance to chemotherapy and radiation treatment. p53 is a pivotal tumor suppressor that induces apoptosis, cell cycle arrest, and senescence in response to various stresses, also playing an important role in the regulation of radiosensitivity. Autophagy may either promote or inhibit the survival of tumor cells, while it was found to change along with the status of p53 in cancer cells. In this mini review, we aimed to provide an overview of the intricate relationship between autophagy and the status of p53 which plays an important role in radiosensitivity. Since autophagy can react to radiation differently in cancer cells with different p53 statuses, future work elucidating the interaction between autophagy and p53 in response to radiation might provide more insight into targeted cancer radiotherapy.

Fabrication of Large-Area Silicon Spherical Microlens Arrays by Thermal Reflow and ICP Etching.

In this paper, we proposed an efficient and high-precision process for fabricating large-area microlens arrays using thermal reflow combined with ICP etching. When the temperature rises above the glass transition temperature, the polymer cylinder will reflow into a smooth hemisphere due to the surface tension effect. The dimensional differences generated after reflow can be corrected using etching selectivity in the following ICP etching process, which transfers the microstructure on the photoresist to the substrate. The volume variation before and after reflow, as well as the effect of etching selectivity using process parameters, such as RF power and gas flow, were explored. Due to the surface tension effect and the simultaneous molding of all microlens units, machining a 3.84 × 3.84 mm2 silicon microlens array required only 3 min of reflow and 15 min of ICP etching with an extremely low average surface roughness Sa of 1.2 nm.

Inductively Coupled Plasma Dry Etching of Silicon Deep Trenches with Extremely Vertical Smooth Sidewalls Used in Micro-Optical Gyroscopes.

Micro-optical gyroscopes (MOGs) place a range of components of the fiber-optic gyroscope (FOG) onto a silicon substrate, enabling miniaturization, low cost, and batch processing. MOGs require high-precision waveguide trenches fabricated on silicon instead of the ultra-long interference ring of conventional F OGs. In our study, the Bosch process, pseudo-Bosch process, and cryogenic etching process were investigated to fabricate silicon deep trenches with vertical and smooth sidewalls. Different process parameters and mask layer materials were explored for their effect on etching. The effect of charges in the Al mask layer was found to cause undercut below the mask, which can be suppressed by selecting proper mask materials such as SiO2. Finally, ultra-long spiral trenches with a depth of 18.1 µm, a verticality of 89.23°, and an average roughness of trench sidewalls less than 3 nm were obtained using a cryogenic process at -100 °C.

Unraveling Colorectal Cancer and Pan-cancer Immune Heterogeneity and Synthetic Therapy Response Using Cuproptosis and Hypoxia Regulators by Multi-omic Analysis and Experimental Validation.

Cuproptosis, a new type of programmed cell death (PCD), is closely related to cellular tricarboxylic acid cycle and cellular respiration, while hypoxia can modulate PCD. However, their combined contribution to tumor subtyping remains unexplored. Here, we applied a multi-omics approach to classify TCGA_COADREAD based on cuproptosis and hypoxia. The classification was validated in three colorectal cancer (CRC) cohorts and extended to a pan-cancer analysis. The results demonstrated that pan-cancers, including CRC, could be divided into three distinct subgroups (cuproptosis-hypoxia subtypes, CHSs): CHS1 had active metabolism and poor immune infiltration but low fibrosis; CHS3 had contrasting characteristics with CHS1; CHS2 was intermediate. CHS1 may respond well to cuproptosis inducers, and CHS3 may benefit from a combination of immunotherapy and anti-fibrosis/anti-hypoxia therapies. In CRC, the CHSs also showed a significant difference in prognosis and sensitivity to classic drugs. Organoid-based drug sensitivity assays validated the results of transcriptomics. Cell-based assays indicated that masitinib and simvastatin had specific effects on CHS1 and CHS3, respectively. A user-friendly website based on the classifier was developed (https://fan-app.shinyapps.io/chs_classifier/) for accessibility. Overall, the classifier based on cuproptosis and hypoxia was applicable to most pan-cancers and could aid in personalized cancer therapy.

A pyroptosis-related signature in colorectal cancer: exploring its prognostic value and immunological characteristics.

Background: The heterogeneity of colorectal cancer (CRC) is the main cause of the disparity of drug sensitivity and the variability of prognosis. Pyroptosis is closely associated with the development and prognosis of various tumors, including CRC. Dividing CRC into distinct subgroups based on pyroptosis is a worthwhile topic for improving the precision treatment and prognosis prediction of CRC. Methods: We classified patients into two clusters using the consensus clustering based on the pyroptosis-related genes (PRGs). Next, the prognostic signature was developed with LASSO regression analysis using the screened genes from differentially expressed genes (DEGs) by univariate and multivariate Cox analyses. According to the pyroptosis-related score (PR score) calculated with the signature, patients belonged to two groups with distinct prognosis. Moreover, we assessed the immune profile to explore the relationship between the signature and immunological characteristics. Two single cell sequencing databases were adopted for further exploration of tumor immune microenvironment (TME). In addition, we applied our own cohort and Drugbank to explore the correlation of the signature and clinical therapies. We also studied the expression of key genes by immunohistochemistry. Results: The signature performed well in predicting the prognosis of CRC as the high area under curve (AUC) value demonstrated. Patients with a higher PR score had poorer prognosis and higher expression of immune checkpoints but more abundant infiltration of immune cells. Combining with the indicator of therapeutic analysis, they might benefit more from immune checkpoint blockade (ICB) and neo-adjuvant chemoradiotherapy (nCRT). Conclusion: In conclusion, our study is based on genomics and transcriptomics to investigate the role of PRGs in CRC. We have established a prognostic signature and integrated single-cell data to study the relationship between the signature with the TME in CRC. Its clinical application in reliable prediction of prognosis and personalized treatment was validated by public and own sequencing cohort. It provided a new insight for the personalized treatment of CRC.

Fabrication of High Precision Silicon Spherical Microlens Arrays by Hot Embossing Process.

In this paper, a high-precision, low-cost, batch processing nanoimprint method is proposed to process a spherical microlens array (MLA). The nanoimprint mold with high surface precision and low surface roughness was fabricated by single-point diamond turning. The anti-sticking treatment of the mold was carried out by perfluorooctyl phosphoric acid (PFOPA) liquid deposition. Through the orthogonal experiment of hot embossing with the treated mold and subsequent inductively coupled plasma (ICP) etching, the microstructure of MLA was transferred to the silicon substrate, with a root mean square error of 17.7 nm and a roughness of 12.1 nm Sa. The average fitted radius of the microlens array units is 406.145 µm, which is 1.54% different from the design radius.

Fabrication of Antireflection Micro/Nanostructures on the Surface of Aluminum Alloy by Femtosecond Laser.

Designed micro-nano structures on the surface of aluminum alloy provide excellent light trapping properties that can be used extensively in thermal photovoltaics, sensors, etc. However, the fabrication of high-performance antireflective micro-nano structures on aluminum alloy is challenging because aluminum has shallow intrinsic losses and weak absorption. A two-step strategy is proposed for fabricating broadband antireflection structures by superimposing nanostructures onto microscale structures. By optimizing the processing parameters of femtosecond laser, the average reflectances of 2.6% within the visible spectral region (400-800 nm) and 5.14% within the Vis-NIR spectral region (400-2500 nm) are obtained.

miR­576­5p promotes epithelial­to­mesenchymal transition in colorectal cancer by targeting the Wnt5a­mediated Wnt/ß­catenin signaling pathway.

Colorectal cancer (CRC) is one of the most common types of malignancy and the third most commonly diagnosed form of cancer worldwide, ranking as the fourth leading cause of cancer­associated mortality. MicroRNA (miR)­576­5p has been reported to be highly expressed in patients with CRC; however, its biological role remains unclear. The present study aimed therefore to investigate the biological role and underlying mechanism of miR­576­5p in CRC cell line SW480. The viability of SW480 cells following transfection with miR­576­5p mimic or inhibitor was analyzed using MTT assay. Wound healing and Transwell assays were performed to determine the cell migratory and invasive abilities, respectively. A dual luciferase reporter assay was used to verify the predicted binding site between miR­576­5p and Wnt5a. Reverse transcription­quantitative PCR and western blotting were used to analyze the expression levels of miR­576­5p, E­cadherin, N­cadherin, vimentin, Snail1, Wnt5a, ß­catenin, c­myc, cyclin D1 and p/t­c­Jun. Using bioinformatics analysis, high expression of miR­576­5p was found not only in tumor tissues, compared with the normal tissue, but also in CRC cells, compared with NCM460 cells. Furthermore, the inhibition of miR­576­5p expression significantly decreased the cell viability and the migratory and invasive abilities of SW480 cells, and suppressed the epithelial­to­mesenchymal transition (EMT). In addition, miR­576­5p could interact with Wnt5a and regulate the expression level of Wnt5a in order to influence the activity of Wnt/ß­catenin signaling. The results from rescue experiments further demonstrated that the effect of miR­576­5p overexpression on cell metastasis and EMT was reversed by Wnt5a overexpression or treatment with XAV­939, which is an inhibitor of the Wnt/ß­catenin signaling pathway. In conclusion, the findings from the present study suggested that inhibition of miR­576­5p may suppress SW480 cell metastasis and EMT by targeting Wnt5a and regulating the Wnt5a­mediated Wnt/ß­catenin signaling pathway, providing a potential therapeutic target for the treatment of CRC.

PLK1 Inhibition Sensitizes Breast Cancer Cells to Radiation via Suppressing Autophagy.

PURPOSE: Polo-like kinase 1 (PLK1) is a protein kinase that is overexpressed in breast cancer and may represent an attractive target for breast cancer treatment. However, few studies have investigated the relationship between PLK1 and radiosensitivity in breast cancer. Here, we attempted to explore whether PLK1 inhibition could sensitize breast cancer cells to radiation. METHODS AND MATERIALS: Breast cancer cells were treated with PLK1 small interference RNA or the PLK1-inhibitor, GSK461364. Cell proliferation was assessed using a colony formation assay. Cell cycle analyses were performed by flow cytometry. DNA damage, autophagy, and reactive oxygen species induced by ionizing radiation were detected by immunofluorescence, Western blot, and flow cytometry, respectively. Microtubule-associated protein 1 light chain 3 alpha (LC3) puncta were detected using an immunofluorescence assay. A clonogenic survival assay was used to determine the effect of PLK1 inhibition on cell radiosensitivity. A xenograft mouse model of breast cancer cells was used to investigate the potential synergistic effects of PLK1 inhibition and irradiation in vivo. Finally, the expression of PLK1 and LC3 in the breast cancer tissues was evaluated by immunohistochemistry. RESULTS: PLK1 inhibition significantly suppressed the proliferation and increased the radiosensitivity of breast cancer cells. Pharmacologic inhibition of PLK1 by the selective inhibitor, GSK461364, enhanced the radiosensitivity of breast cancer cells in vivo (n = 4, P = .002). Mechanistically, PLK1 inhibition led to the downregulation of radiation-induced reactive oxygen species and autophagy, thereby increasing the radiosensitivity of breast cancer cells. Additionally, we detected a positive correlation between the expression of PLK1 and LC3 in human breast cancer samples (n = 102, R = 0.486, P = .005). CONCLUSIONS: Our findings indicate that PLK1 inhibition enhances the radiosensitivity of breast cancer cells in a manner associated with the suppression of radiation-induced autophagy. The inhibition of PLK1 represents a promising strategy for radiosensitizing breast cancer.

Comparison of the efficacy between concurrent chemoradiotherapy with or without adjuvant chemotherapy for stage II nasopharyngeal carcinoma.

BACKGROUND: Although common, the use of concurrent chemoradiotherapy with adjuvant chemotherapy for stage II nasopharyngeal carcinoma (NPC) is controversial due to its undefined clinical benefits. We, therefore, conducted a retrospective cohort study to investigate whether adjuvant chemotherapy confers survival gains to stage II NPC patients. METHODS: In this study, we examined whether combining adjuvant chemotherapy (AC) and/or concurrent chemotherapy with radiotherapy (CCRT) improved survival in patients with stage II NPC. Three hundred thirty-five stage II NPC patients were retrospectively analyzed between June 2003 and June 2016 and received CCRT; some patient groups also received AC every 3 weeks for 2 to 3 cycles. RESULTS: The median follow-up duration was 72 months for all patients (range, 26-151 months) and the estimated 5-year locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 95.1%, 97.8%, 93.5%, and 94.3%. At the last follow-up, there were no statistically significant differences among the CCRT and CCRT+AC groups in 5-year LRRFS (95.2% vs 94.9%, P = .599), DMFS (98.5% vs 92.4%, P = .152), PFS (93.8% vs 90.2%, P = .599), or OS (95.5% vs 93.9%, P = .682) rates. CONCLUSION: The analyses revealed that a combined regimen was not an independent prognostic factor for any survival outcome. However, patients who received CCRT plus AC experienced more acute adverse events than those who received CCRT alone. Thus, the addition of AC to CCRT did not improve survival outcomes, but was associated with higher incidences of acute treatment-associated toxicities than CCRT alone in patients with stage II NPC.

Outcome and Optimal Treatment for Esthesioneuroblastoma in the Era of Intensity-Modulated Radiation Therapy: A Single-Center Experience.

PURPOSE: Esthesioneuroblastoma (ENB) is a type of rare malignant neoplasm of the sinonasal cavity. Optimal treatment for ENB is still controversial. A retrospective study was conducted to identify the clinical outcome and optimal treatment for ENB in the era of intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: Between December 2006 and August 2018, 37 patients with ENB without distant metastasis who underwent neoadjuvant chemotherapy followed by chemoradiotherapy (C+RC) or surgery followed by radiotherapy or chemoradiotherapy (S+R/RC) were retrospectively reviewed at our center. RESULTS: The median follow-up period was 63.7 months (range, 13.2-111.5 months). Five-year overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were similar between treatment arms (P values > 0.05). With a multivariate analysis, a Karnofsky Performance Status (KPS) of ≤80 was a prognostic factor for poor five-year OS. A KPS of ≤80 and Kadish class C-D tumors were prognostic factors for poor PFS. A KPS of ≤80 was a prognostic factor for poor LRFS. When KPS was ≤80 and tumors were Kadish class C-D, T3-4 and N1 were prognostic factors for poor DMFS. Subgroup analyses also demonstrated that the two treatment arms exhibited similar trends for OS, PFS, LRFS, and DMFS, excluding patients with N1 or Kadish class A-B tumors (P values > 0.05). CONCLUSION: In the era of IMRT, S+R/RC failed to improve the outcomes of patients with ENB. C+RC may be a feasible treatment option for patients with ENB.

Screening of significant biomarkers with poor prognosis in hepatocellular carcinoma via bioinformatics analysis.

Hepatocellular carcinoma (HCC) is a malignant tumor with unsatisfactory prognosis. The abnormal genes expression is significantly associated with initiation and poor prognosis of HCC. The aim of the present study was to identify molecular biomarkers related to the initiation and development of HCC via bioinformatics analysis, so as to provide a certain molecular mechanism for individualized treatment of hepatocellular carcinoma.Three datasets (GSE101685, GSE112790, and GSE121248) from the GEO database were used for the bioinformatics analysis. Differentially expressed genes (DEGs) of HCC and normal liver samples were obtained using GEO2R online tools. Gene ontology term and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis were conducted via the Database for Annotation, Visualization, and Integrated Discovery online bioinformatics tool. The protein-protein interaction (PPI) network was constructed by the Search Tool for the Retrieval of Interacting Genes database and hub genes were visualized by Cytoscape. Survival analysis and RNA sequencing expression were conducted by UALCAN and Gene Expression Profiling Interactive Analysis.A total of 115 shared DEGs were identified, including 30 upregulated genes and 85 downregulated genes in HCC samples. P53 signaling pathway and cell cycle were the major enriched pathways for the upregulated DEGs whereas metabolism-related pathways were the major enriched pathways for the downregulated DEGs. The PPI network was established with 105 nodes and 249 edges and 3 significant modules were identified via molecular complex detection. Additionally, 17 candidate genes from these 3 modules were significantly correlated with HCC patient survival and 15 of 17 genes exhibited high expression level in HCC samples. Moreover, 4 hub genes (CCNB1, CDK1, RRM2, BUB1B) were identified for further reanalysis of KEGG pathway, and enriched in 2 pathways, the P53 signaling pathway and cell cycle pathway.Overexpression of CCNB1, CDK1, RRM2, and BUB1B in HCC samples was correlated with poor survival in HCC patients, which could be potential therapeutic targets for HCC.

Adjuvant chemotherapy for locally advanced rectal cancer in elderly patients after neoadjuvant chemoradiotherapy and surgery: Toxicity and survival outcomes.

The treatment strategy for elderly patients with locally advanced rectal cancer (LARC) remains controversial. The aim of this study was to identify the significance of adjuvant chemotherapy (AC) for elderly patients with LARC after neoadjuvant chemoradiotherapy (nCRT) and surgical resection. Between February 2002 and December 2012, a total of 43 patients aged ≥70 years with LARC following nCRT and surgery were retrospectively reviewed. The median follow-up time was 51 months (range 15-161 months). All patients completed the programmed chemoradiotherapy, of which 20 patients (46.5%) received 5-fluorouracil-based AC, and other 23 patients (53.5%) received no adjuvant chemotherapy. The 5-year overall survival and disease-free survival rates for AC group and non-adjuvant chemotherapy (NAC) group were 74.7% vs 63.4% (P = .562) and 73.4% vs 66.3% (P = .445), respectively. More patients in AC group suffered from severe leucopenia than that in NAC group (60% vs 17.4%, P = .004). For elderly patients with LARC following nCRT and surgery, AC may not benefit for survival, but increase treatment related leucopenia.

Methodology of dose calculation for external beam radiation combined with high dose rate brachytherapy in the era of 3-dimensional treatment planning system.

Intracavitary application of brachytherapy (BT) sources followed by external beam radiation is essential for the local treatment of carcinoma of the cervix, postate, and nasopharynx. Dose distribution of external beam radiation plus BT can be challenging for the planning system because of their dose calculation by 2 different treatment planning system (TPS). The aims of this study were to introduce a novel iterative method of dose calculation preformed in the Pinnacle plan and evaluate a combined dose distribution for external beam radiation and BT.Because it is often the goal of the planner to produce plan with uniform dose throughout the target volume and normal tissue, we present an Iridium-192 calculation program using American Association of Physicists in Medicine Task Group 43 formula and export it to other commercialized TPS though the combined dose distribution of external beam radiation and BT can be shown. To illustrate such an improved procedure, we present the treatment plans of 2 patients treated with external beam radiation plus BT.Dose distribution of the single BT source were calculated with the Plato post loading TPS and the program model, and the results of 2 methods were similar. A nasopharyngeal case and a cervical case were shown in Pinnacle with this program. The total dose distribution of BT combined with EBRT was showed in compute tomography images. And the corresponding dose volume histogram figures could be displayed correctly in Pinnacle TPS.We demonstrated a novel iterative method of dose calculation preformed in the Pinnacle plan to produce a combined dose distribution for external beam radiation and BT. We used it to evaluate the dose of target volume and normal tissues in the treatment of external beam radiation plus BT.