p97/VCP is highly expressed in the stem-like cells of breast cancer and controls cancer stemness partly through the unfolded protein response

p97/VCP, an evolutionarily concerned ATPase, partakes in multiple cellular proteostatic processes, including the endoplasmic reticulum (ER)-associated protein degradation (ERAD). Elevated expression of p97 is common in many cancers and is often associated with poor survival. Here we report that the levels of p97 positively correlated with the histological grade, tumor size, and lymph node metastasis in breast cancers. We further examined p97 expression in the stem-like cancer cells or cancer stem cells (CSCs), a cell population that purportedly underscores cancer initiation, therapeutic resistance, and recurrence. We found that p97 was consistently at a higher level in the CD4

PMMTalk: Speech-Driven 3D Facial Animation from Complementary Pseudo Multi-modal Features

Speech-driven 3D facial animation has improved a lot recently while most related works only utilize acoustic modality and neglect the influence of visual and textual cues, leading to unsatisfactory results in terms of precision and coherence. We argue that visual and textual cues are not trivial information. Therefore, we present a novel framework, namely PMMTalk, using complementary Pseudo Multi-Modal features for improving the accuracy of facial animation. The framework entails three modules: PMMTalk encoder, cross-modal alignment module, and PMMTalk decoder. Specifically, the PMMTalk encoder employs the off-the-shelf talking head generation architecture and speech recognition technology to extract visual and textual information from speech, respectively. Subsequently, the cross-modal alignment module aligns the audio-image-text features at temporal and semantic levels. Then PMMTalk decoder is employed to predict lip-syncing facial blendshape coefficients. Contrary to prior methods, PMMTalk only requires an additional random reference face image but yields more accurate results. Additionally, it is artist-friendly as it seamlessly integrates into standard animation production workflows by introducing facial blendshape coefficients. Finally, given the scarcity of 3D talking face datasets, we introduce a large-scale 3D Chinese Audio-Visual Facial Animation (3D-CAVFA) dataset. Extensive experiments and user studies show that our approach outperforms the state of the art. We recommend watching the supplementary video

Comparison of survival, acute toxicities, and dose-volume parameters between intensity-modulated radiotherapy with or without internal target volume delineation method and three-dimensional conformal radiotherapy in cervical cancer patients:A retrospective and propensity score-matched analysis

BACKGROUND: To evaluate whether the use of the internal target volume (ITV) delineation method improves the performance of intensity‐modulated radiotherapy (IMRT) and three‐dimensional conformal radiotherapy (3DCRT) in terms of survival, acute toxicities, and dose–volume parameters. METHODS: A total number of 477 cervical cancer patients who received concurrent chemoradiotherapy (CCRT) from January 2012 to December 2016 were retrospectively analyzed. They were divided into four groups: the non‐ITV (N‐ITV) + IMRT, ITV + IMRT, N‐ITV + 3DCRT, and ITV + 3DCRT groups, with 76, 41, 327, and 33 patients, respectively. Survival analysis was performed with the Kaplan–Meier and the log‐rank tests, and acute toxicity analysis was performed with the chi‐squared test and the binary logistic regression test. Using the propensity score matching (PSM) method, 92 patients were matched among the four groups, and their dose–volume parameters were assessed with the Kruskal–Wallis method. RESULTS: The median follow‐up time was 49 months (1–119) for overall survival (OS). The 5‐year OS rate was 66.4%. The ITV delineation method was an independent prognostic factor for OS (HR [95% CI]: 0.52 [0.27, 0.98], p = 0.044) and progression‐free survival (PFS) (HR [95% CI]: 0.59 [0.36, 0.99], p = 0.045). The ITV + IMRT group had the lowest incidence rate (22%) and the N‐ITV + IMRT group had the highest incidence rate of grade ≥3 hematological toxicity (HT) (46.1%) among the four groups. The pelvic bone marrow relative V10, V20, and V30 in the N‐ITV + IMRT group was higher than those in the ITV + IMRT and N‐ITV + 3DCRT groups (p < 0.05). CONCLUSIONS: The use of ITV for IMRT treatment planning was associated with improved overall survival and progression‐free survival, with lower HT rate

MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma

<p>Abstract</p> <p>Background</p> <p>MiR-221 and miR-222 (miR-221/222) are frequently up-regulated in various types of human malignancy including glioblastoma. Recent studies have reported that miR-221/222 regulate cell growth and cell cycle progression by targeting p27 and p57. However the underlying mechanism involved in cell survival modulation of miR-221/222 remains elusive.</p> <p>Results</p> <p>Here we showed that miR-221/222 inhibited cell apoptosis by targeting pro-apoptotic gene PUMA in human glioma cells. Enforced expression of miR-22/222 induced cell survival whereas knockdown of miR-221/222 rendered cells to apoptosis. Further, miR-221/222 reduced PUMA protein levels by targeting PUMA-3'UTR. Introducing PUMA cDNA without 3'UTR abrogated miR-221/222-induced cell survival. Notably, knockdown of miR-221/222 induces PUMA expression and cell apoptosis and considerably decreases tumor growth in xenograft model. Finally, there was an inverse relationship between PUMA and miR-221/222 expression in glioma tissues.</p> <p>Conclusion</p> <p>To our knowledge, these data indicate for the first time that miR-221/222 directly regulate apoptosis by targeting PUMA in glioblastoma and that miR-221/222 could be potential therapeutic targets for glioblastoma intervention.</p

Correlation between gene mutation status and clinicopathologic features in early multiple primary lung cancer

ObjectiveTo understand the characteristics of genetic mutation in multiple primary lung cancer so as to guide clinical decisions in targeted therapy.MethodsWe analyzed a total of 265 tumors from 111 patients who underwent surgery for multiple lung cancers. Individual tumors were subjected to histological evaluation and gene mutation analysis using ABI 7500 Fluorescence quantitative PCR.ResultsIn this study, we analyzed demographic and clinical parameters such as age, gender, smoking, alcohol consumption, pathological type, number of nodules, and other details of 111 patients with early multiple primary lung cancer. We also compared the clinicopathologic characteristics of different populations based on the gene mutation status of pulmonary nodules. Subsequently, we performed a clinicopathological analysis of all 265 pulmonary nodules from these patients. Results showed significant differences in clinicopathological features of pulmonary nodules in different genetic mutations.ConclusionThis study revealed the gene mutation characteristics and clinicopathological features in early multiple primary lung cancer. We found that the gene mutation status between different nodules in patients with early multiple primary lung cancer was inconsistent in most cases. Therefore, the use of targeted therapy based on the genetic sequencing of only one nodule, is unreliable. We hope this study can be helpful in guiding clinical treatment decisions

Rab25-Mediated EGFR Recycling Causes Tumor Acquired Radioresistance.

Tumor acquired radioresistance remains as the major limit in cancer radiotherapy (RT). Rab25, a receptor recycling protein, has been reported to be enhanced in tumors with aggressive phenotype and chemotherapy resistance. In this study, elevated Rab25 expression was identified in an array of radioresistant human cancer cell lines, in vivo radioresistant xenograft tumors. Clinical investigation confirmed that Rab25 expression was also associated with a worse prognosis in patients with lung adenocarcinoma (LUAD) and nasopharyngeal carcinoma (NPC). Enhanced activities of EGFR were observed in both NPC and LUAD radioresistant cells. Rab25 interacts with EGFR to enhance EGFR recycling to cell surface and to decrease degradation in cytoplasm. Inhibition of Rab25 showed synergized radiosensitivity with reduced aggressive phenotype. This study provides the clinical and experimental evidence that Rab25 is a potential therapeutic target to alleviate the hyperactive EGFR signaling and to prevent RT-acquired tumor resistance in patients with LUAD and NPC