bims-netuvo 2022-07-31 papers

Cancer Discov. 2022 Jul 26. pii: CD-21-1690. [Epub ahead of print]

Reprogrammed Schwann cells organize into dynamic tracks that promote pancreatic cancer invasion.

Sylvie Deborde, Laxmi Gusain, Ann Powers, Andrea Marcadis, Yasong Yu, Chun-Hao Chen, Anna Frants, Elizabeth Kao, Laura H Tang, Efsevia Vakiani, Masataka Amisaki, Vinod P Balachandran, Annalisa Calo, Tatiana Omelchenko, Kristjan R Jessen, Boris Reva, Richard J Wong.

Nerves are a component of the tumor microenvironment contributing to cancer progression, but the role of cells from nerves in facilitating cancer invasion remains poorly understood. Here we show that Schwann cells (SCs) activated by cancer cells collectively function as Tumor Activated Schwann cell Tracks (TASTs) that promote cancer cell migration and invasion. Non-myelinating SCs form TASTs and have cell gene expression signatures that correlate with diminished survival in patients with pancreatic ductal adenocarcinoma. In TASTs, dynamic SCs form tracks that serve as cancer pathways and apply forces on cancer cells to enhance cancer motility. These SCs are activated by c-Jun, analogous to their reprogramming during nerve repair. This study reveals a mechanism of cancer cell invasion that co-opts a wound repair process and exploits the ability of SCs to collectively organize into tracks. These findings establish a novel paradigm of how cancer cells spread and reveal therapeutic opportunities.

DOI: https://doi.org/10.1158/2159-8290.CD-21-1690

Front Oncol. 2022 ;12 927262

Association of Mu-Opioid Receptor Expression With Long-Term Survival and Perineural Nerve Invasion in Patients Undergoing Surgery for Ovarian Cancer.

Hao Zhang, Mengdi Qu, Caihong Sun, Yanghanzhao Wang, Ting Li, Wei Xu, Zhirong Sun, Xiaoguang Zhang, Kefang Guo, Wankun Chen, Minli Sun, Changhong Miao.

Background: Opioids are widely used during primary debulking surgery (PDS) for ovarian cancers, and a high mu-opioid receptor (MOR) expression predicts worse cancer outcomes. However, the impact of MOR expression on survival outcomes in ovarian cancers is still not clear.
Methods: A retrospective cohort study was conducted in patients who underwent PDS in ovarian cancer patients. MOR expression was measured in tumor and normal tissue. Primary outcomes were overall survival (OS) and disease-free survival (DFS). Secondary outcomes included perineural invasion (PNI), intraoperative sufentanil consumption, length of stay (LOS), and verbal numerical rating scale (VNRS) on postoperative day 1 (POD1), POD3, and POD5.
Results: After propensity score matching, a total of 366 patients were finally enrolled in this study. There were no significant differences in OS rates in patients with high versus low levels of MOR (1-year OS: 82.9% versus 83.3%, 3-year: 57.8% versus 59.1%, 5-year: 22.4% versus 23.1%,respectively) in the ovarian cancers. There were no significant differences in DFS between the groups. Intraoperative sufentanil consumption was higher in the MOR high-expression group compared with the MOR low-expression group. Tumors expressing high levels of MOR showed higher rates of PNI. VNRS in the MOR high-expression group was higher on POD1.
Conclusion: MOR is not an independent predictor of worse survival in ovarian cancers but is associated with high rates of perineural invasion.

Keywords: disease-free survival; mu-opioid receptor; ovarian cancer; overall survival; surgery

DOI: https://doi.org/10.3389/fonc.2022.927262

Oncol Res Treat. 2022 Jul 26.

Role of chemoradiation (CRT) in the adjuvant treatment of radically resected pancreatic cancer (PC) patients: a mono-institutional retrospective analysis.

Gian Carlo Mattiucci, Lisa Salvatore, Andrea D'Aviero, Cinzia Bagalà, Maria Bensi, Francesco Mosè Castronovo, Francesco Cellini, Paola De Franco, Brunella Di Stefano, Gabriella Macchia, Valeria Masiello, Roberta Menghi, Giuseppe Quero, Sara Reina, Alessio Giuseppe Morganti, Sergio Alfieri, Giampaolo Tortora, Vincenzo Valentini.

Introduction Pancreatic cancer (PC) represents an unfavorable prognosis condition, even in patients with resectable disease. The aim of this series was to investigate the role of treatment intensification with adjuvant chemoradiation (CRT) in radically resected PC patients. Methods Data from PC patients undergone radical surgery, adjuvant chemotherapy (CT) and CRT throughout a 20-year period were retrospectively collected. Actuarial local control (LC) and the overall survival (OS) were the primary endpoints, with disease-free-survival (DFS) and metastases-free-survival (MFS) representing secondary end-points. Results The analysis included 108 PC patients treated with adjuvant CRT and CT from January 2000 to August 2019. Median age was 66 years (range: 40-83), all patients underwent radical surgical resection with adjuvant chemotherapy (88, 81,5%) plus concomitant chemoradiation (101, 93,5%) or radiotherapy alone (7, 6,5%). The median dose delivered on tumor bed was 50,4 Gy (range: 45-50,6 Gy), while median dose on regional lymphatic drainage stations was 39,6 Gy (range 39,6-45 Gy. Concomitant CT was gemcitabine-based regimen in the vast majority of patients (87, 80.6%). Median follow-up time was 21 months; the 2- and 5-years LC rate were 75,8% and 59,1%, respectively. Perineural invasion (PNI) at pathological assessment was found significantly associated to LC (p=0.028). Median OS was 40 months with 2- and 5-years OS rate of 73.9% and 41,6 % respectively. Conclusions The outcomes of this series suggest to investigate the possible impact of adding adjuvant CRT to CT in PC patients. Timing, combination of modern CRT with new systemic therapies need to be further investigated to personalize therapy and optimize clinical advantages.

DOI: https://doi.org/10.1159/000525945

PLoS One. 2022 ;17(7): e0271629

Anatomic location of colorectal cancer presents a new paradigm for its prognosis in African American patients.

Donghai Wang, Raag Agrawal, Shuli Zou, M A Haseeb, Raavi Gupta.

Among all racial groups in the U.S., African Americans (AA) have the highest incidence of and mortality from colorectal cancer (CRC). Although socioeconomic factors, as the major contributors to racial disparity of CRC, have been widely investigated, there is a dearth of information germane to understanding its biological basis. To better elucidate the clinicopathologic features we extracted demographic, clinical, pathologic and molecular features of 500 consecutive cases of CRC diagnosed at our institution which has an AA-predominant patient population (75% of all patients). We compared data from our AA patients with those of white patients both from our institution and from SEER and the published literature for meaningful comparison. AA patients were more likely to be at an advanced disease stage (25.9% vs. 20.8%, p = 0.041), have low grade tumors (89.2% vs. 77.5%, p<0.001) in cecum (18.7% vs. 16.2%, p<0.001) and <60-years-old than white patients (31.8% vs. 26.3%, p = 0.015). The frequency of KRAS mutation was higher in AA patients than in white patients (56.8% vs. 20.7%, p<0.001). Amongst subtypes of KRAS tested in CRC, codon 12 mutation is more common in AA than white patients (85.2% vs. 68.9%, p = 0.020). Compared with other racial groups, we found AA patients to have worse disease-free survival (HR = 3.682, p = 0.035). Also, AA patients with CRC in distal (sigmoid and rectum) or proximal (cecum) colon have worse overall survival than those with CRC in middle colon (HR = 2.926, p = 0.014), a finding not observed in white patients. In both racial groups, advanced stage, perforation, and hypertension were independent prognostic factors for overall survival (p<0.05). Similarly, low body-mass index at presentation, mucinous adenocarcinoma, lymphovascular invasion, perineural invasion and KRAS mutations were independent factors significantly associated with poor disease-free survival. Collectively, our data provide new insights into the roles of clinicopathologic features, especially anatomic distribution, in predicting outcomes of CRC in AA population.

DOI: https://doi.org/10.1371/journal.pone.0271629