Impact of embedded medication assistance program specialists on medication access in outpatient oncology clinics.

INTRODUCTION: Medication prior authorizations (PA) required by insurance payers can be time-consuming to complete and may lead to delays in treatment for cancer patients. The primary objective of this study is to assess the impact of Medication Assistance Program (MAP) specialists embedded in adult hematology and oncology clinics on the PA and financial assistance process. METHODS: This was a retrospective chart review study performed at a large academic medical center that examined medication referrals completed by MAP specialists in four hematology and oncology clinics. The primary outcome was the median PA turnaround time, defined as time from initial referral creation to final referral completion. Secondary outcomes assessed median turnaround time for financial assistance programs and total patient savings. RESULTS: A total of 176 prior authorization, 92 manufacturer patient assistance program (PAP), and 37 copay assistance referrals were completed. The median turnaround times were 24, 154, and 19 hours for PA, manufacturer PAP, and copay assistance program referrals, respectively. Total cost savings amounted to over $1.8 million for patients approved to receive medications through manufacturer PAPs. CONCLUSIONS: Embedding MAP specialists in adult hematology/oncology clinics supports an efficient and timely process for PA approvals while also providing patient cost-savings.

Clinical judgment is a cornerstone for validating and using clinical prediction rules: a head-to-head study on ambulation outcomes for spinal cord injured patients.

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: Clinical prediction rules (CPRs) are an effervescent topic in the medical literature. Recovering ambulation after a traumatic spinal cord injury (tSCI) is a priority for patients and multiple CPRs have been proposed for predicting ambulation outcomes. Our objective is to confront clinical judgment to an established CPR developed for patients with tSCI. SETTINGS: Level one trauma center specialized in tSCI and its affiliated rehabilitation center. METHOD: In this retrospective comparative study, six physicians had to predict the ambulation outcome of 68 patients after a tSCI based on information from the acute hospitalization. Ambulation was also predicted according to the CPR of van Middendorp (CPR-vM). The success rate of the CPR-vM and clinicians to predict ambulation was compared using criteria of 5% for defining clinical significance, and a level of statistical significance of 0.05 for bilateral McNemar tests. RESULTS: There was no statistical difference between the overall performance of physicians (success rate of 79%) and of the CPR-vM (81%) for predicting ambulation. The differences between the CPR-vM and physicians varied clinically and significantly with the level of experience, clinical setting, and field of expertise. CONCLUSION: Confronting CPRs with the judgment of a group of clinicians should be an integral part of the design and validation of CPRs. Head-to-head comparison of CPRs with clinicians is also a cornerstone for defining the optimal strategy for translation into the clinical practice, and for defining which clinician and specific clinical context would benefit from using the CPR.

Multi-omics Reveal that c-Src Modulates the Mitochondrial Phosphotyrosine Proteome and Metabolism According to Nutrient Availability.

BACKGROUND/AIMS: Src kinase family members, including c-Src, are involved in numerous signaling pathways and have been observed inside different cellular compartments. Notably, c-Src modulates carbohydrate and fatty acid metabolism and is involved in the metabolic rewiring of cancer cells. This kinase is found within mitochondria where it targets different proteins to impact on the organelle functions and overall metabolism. Surprisingly, no global metabolic characterization of Src has been performed although c-Src knock-out mice have been available for 30 years. Considering that c-Src is sensitive to various metabolites, c-Src might represent a crucial player in metabolic adjustments induced by nutrient stress. The aim of this work was to characterize the impact of c-Src on mitochondrial activity and overall metabolism using multi-omic characterization. METHODS: Src+/+ and Src-/- mice were fed ad libitum or fasted during 24h and were then analyzed using multi-omics. RESULTS: We observed that deletion of c-Src is linked to lower phosphorylation of Y412-NDUFA8, inhibition of oxygen consumption and accumulation of metabolites involved in glycolysis, TCA cycle and amino acid metabolism in mice fed ad libitum. Finally, metabolomics and (phosphotyrosine) proteomics are differently impacted by Src according to nutrient availability. CONCLUSION: The findings presented here highlight that c-Src reduces mitochondrial metabolism and impacts the metabolic adjustment induced by nutrient stress.

The Endocannabinoid Metabolite Prostaglandin E2 (PGE2)-Glycerol Inhibits Human Neutrophil Functions: Involvement of Its Hydrolysis into PGE2 and EP Receptors.

The endocannabinoids 2-arachidonoyl-glycerol and N-arachidonoyl-ethanolamine mediate an array of pro- and anti-inflammatory effects. These effects are related, in part, to their metabolism by eicosanoid biosynthetic enzymes. For example, N-arachidonoyl-ethanolamine and 2-arachidonoyl-glycerol can be metabolized by cyclooxygenase-2 into PG-ethanolamide (PG-EA) and PG-glycerol (PG-G), respectively. Although PGE2 is a recognized suppressor of neutrophil functions, the impact of cyclooxygenase-derived endocannabinoids such as PGE2-EA or PGE2-G on neutrophils is unknown. This study's aim was to define the effects of these mediators on neutrophil functions and the underlying cellular mechanisms involved. We show that PGE2-G, but not PGE2-EA, inhibits leukotriene B4 biosynthesis, superoxide production, migration, and antimicrobial peptide release. The effects of PGE2-G were prevented by EP1/EP2 receptor antagonist AH-6809 but not the EP4 antagonist ONO-AE2-227. The effects of PGE2-G required its hydrolysis into PGE2, were not observed with the non-hydrolyzable PGE2-serinol amide, and were completely prevented by methyl-arachidonoyl-fluorophosphate and palmostatin B, and partially prevented by JZL184 and WWL113. Although we could detect six of the documented PG-G hydrolases in neutrophils by quantitative PCR, only ABHD12 and ABHD16A were detected by immunoblot. Our pharmacological data, combined with our protein expression data, did not allow us to pinpoint one PGE2-G lipase, and rather support the involvement of an uncharacterized lipase and/or of multiple hydrolases. In conclusion, we show that PGE2-G inhibits human neutrophil functions through its hydrolysis into PGE2, and by activating the EP2 receptor. This also indicates that neutrophils could regulate inflammation by altering the balance between PG-G and PG levels in vivo.

Mammaglobin 1 promotes breast cancer malignancy and confers sensitivity to anticancer drugs.

Mammaglobin 1 (MGB1), a member of the secretoglobin family, is expressed in mammary epithelial tissues and is overexpressed in most mammary carcinomas. Despite the extensive research correlating MGB1 expression profiles to breast cancer pathogenesis and disease outcome, the biological significance of MGB1 in cancer processes is still unclear. We have thus set out to conduct a functional evaluation of the molecular and cellular roles of MGB1 in breast cancer processes leading to disease progression. Using a series of breast cancer cell models with conditional MGB1 expression, we demonstrate that MGB1 promotes cancer cell malignant features. More specifically, loss of MGB1 expression resulted in a decrease of cell proliferation, soft agar spheroid formation, migration, and invasion capacities of breast cancer cells. Concomitantly, we also observed that MGB1 expression activates signaling pathways mediated by MAPK members (p38, JNK, and ERK), the focal adhesion kinase (FAK), matrix metalloproteinases (MMPs) and NFκB. Moreover, MGB1 regulates epithelial to mesenchymal (EMT) features and modulates Snail, Twist and ZEB1 expression levels. Interestingly, we also observed that expression of MGB1 confers breast cancer cell sensitivity to anticancer drug-induced apoptosis. Together, our results support a role for MGB1 in tumor malignancy in exchange for chemosensitivity. These findings provide one of the first descriptive overview of the molecular and cellular roles of MGB1 in breast cancer processes and may offer new insight to the development of therapeutic and prognostic strategies in breast cancer patients. © 2015 Wiley Periodicals, Inc.

Dibenz[b,f]oxepin and Antimycobacterial Chalcone Constituents of Empetrum nigrum.

Two new dibenz[b,f]oxepins, empetroxepins A and B (1 and 2), and seven known compounds (3-9) were isolated from an extract of the Canadian medicinal plant Empetrum nigrum that significantly inhibited the growth of Mycobacterium tuberculosis H37Ra. The structures of 1 and 2 were established through analysis of NMR and MS data. The antimycobacterial activity of the plant extract was attributed primarily to the presence of two chalcone derivatives (6 and 7) that exhibited selective antimycobacterial activity (IC50 values of 23.8 and 32.8 µM, respectively) in comparison to mammalian (HEK 293) cells (IC50 values of 109 and 249 µM, respectively).

Adjuvant therapy in early-stage endometrial cancer: a systematic review of the evidence, guidelines, and clinical practice in the U.S.

Endometrial cancer is the most common gynecologic malignancy in the U.S., with an increasing incidence likely secondary to the obesity epidemic. Surgery is usually the primary treatment for early stage endometrial cancer, followed by adjuvant therapy in selected cases. This includes radiation therapy [RT] with or without chemotherapy, based on stratification of patients into categories dependent on their future recurrence risk. Several prospective trials (PORTEC-1, GOG#99, and PORTEC-2) have shown that the use of adjuvant RT in the intermediate risk (IR) and the high-intermediate risk (HIR) groups decreases locoregional recurrence (LRR) but has no effect on overall survival. The ad hoc analyses from these studies have shown that an even larger LRR risk reduction was seen within the HIR group compared with the IR group. Vaginal brachytherapy is as good as external beam radiotherapy in controlling vaginal relapse where the majority of recurrence occur, and with less toxicity. In the high-risk group, multimodality therapy (chemotherapy and RT) may play a significant role. Although adjuvant RT has been evaluated in many cost-effectiveness studies, high-quality data in this area are still lacking. The uptake of the above prospective trial results in the U.S. has not been promising. Factors that are driving current practices and defining quality-of-care measures for patients with early-stage disease are what future studies need to address.

Targeting LxCxE cleft pocket of retinoblastoma protein in M2 macrophages inhibits ovarian cancer progression.

Ovarian cancer remains a major health threat with limited treatment options available. It is characterized by immunosuppressive tumor microenvironment (TME) maintained by tumor- associated macrophages (TAMs) hindering anti-tumor responses and immunotherapy efficacy. Here we show that targeting retinoblastoma protein (Rb) by disruption of its LxCxE cleft pocket, causes cell death in TAMs by induction of ER stress, p53 and mitochondria-related cell death pathways. A reduction of pro-tumor Rb high M2-type macrophages from TME in vivo enhanced T cell infiltration and inhibited cancer progression. We demonstrate an increased Rb expression in TAMs in women with ovarian cancer is associated with poorer prognosis. Ex vivo, we show analogous cell death induction by therapeutic Rb targeting in TAMs in post-surgery ascites from ovarian cancer patients. Overall, our data elucidates therapeutic targeting of the Rb LxCxE cleft pocket as a novel promising approach for ovarian cancer treatment through depletion of TAMs and re-shaping TME immune landscape. Statement of significance: Currently, targeting immunosuppressive myeloid cells in ovarian cancer microenvironment is the first priority need to enable successful immunotherapy, but no effective solutions are clinically available. We show that targeting LxCxE cleft pocket of Retinoblastoma protein unexpectedly induces preferential cell death in M2 tumor-associated macrophages. Depletion of immunosuppressive M2 tumor-associated macrophages reshapes tumor microenvironment, enhances anti-tumor T cell responses, and inhibits ovarian cancer. Thus, we identify a novel paradoxical function of Retinoblastoma protein in regulating macrophage viability as well as a promising target to enhance immunotherapy efficacy in ovarian cancer.

Identification of a novel promyelocytic leukemia zinc-finger isoform required for colorectal cancer cell growth and survival.

Promyelocytic leukemia zinc-finger (PLZF) is a transcriptional repressor that regulates proliferation, differentiation and apoptosis among various cellular origins. PLZF expression is upregulated in colorectal cancer cell lines but its putative functional role in this context is unknown. Here, we report the identification of a novel p65 PLZF isoform that results from the usage of an evolutionarily conserved alternative translational initiation site. This isoform is devoid of the classical BTB/POZ domain required for nuclear localization and transcriptional repression. Depletion of p65 PLZF expression in colorectal cancer cell lines results in reduction of cell growth, loss of cell anchorage and increase in cell apoptosis. Overall, these results indicate that p65 PLZF is crucial to maintain colorectal cancer cell adhesion as well as survival and must occur independently of the traditionally viewed transcriptional role of PLZF in the course of these biological processes.

Anterior Elbow Heterotopic Ossification in Patient With Pemphigus Vulgaris: An Unheard Complication of a Rare Condition.

Pemphigus vulgaris is a potentially fatal disease within the epidermis with rare noncutaneous manifestations. Heterotopic ossification has not been previously described as one of the inherent complications of this skin pathology. A 44-year-old man presented with severe pemphigus vulgaris involving 80 to 90% of his body surface area. He had an extended time to wound closure of 5 months, as well as two additional months bed bound due to related infectious and respiratory complications. He progressively developed a worsening range of motion at his bilateral elbows. X-ray demonstrated bilateral anterior elbow heterotopic ossification. Passive and active range of motion exercises were initiated early in the course of his treatment and only yielded a small positive effect. Thus, screening for heterotopic ossification may be warranted when a significant joint range of motion is lost in cases of autoimmune cutaneous disease, and even more in the presence of severe open wounds with delayed wound closure.

Novel Design and Implementation of an Integrated Burn Rehabilitation Clinical Fellowship.

ABSTRACT: Postgraduate medical burn rehabilitation training has been limited, with very few academic physiatrists specializing in burn rehabilitation. As a result, there are no existing models for postgraduate burn rehabilitation education. A 12-mo comprehensive clinical fellowship in burn rehabilitation was offered through a tertiary burn center with formal university accreditation. In this article, the clinical, educational, and skill-based goals developed and implemented for this novel fellowship was outlined to serve as a blueprint for future fellowships in burn rehabilitation, as well as reflections on the experience.

Burn Injury Complications Impacting Rehabilitation.

Successful post-burn rehabilitation requires an understanding of a wide range of complications to maximize functional recovery. This article reviews a range of potential challenges including burn scar contracture, amputation, peripheral nerve injury, heterotopic ossification, dysphagia, altered skin physiology, pain, and pruritis. The overall focus is to serve as a guide for post-injury therapy and rehabilitation spanning the phases of care and considering evidence-based approaches, prevention, and treatment with an ultimate goal of aiding in the functional recovery and long-term quality of life for burn survivors.

Assessment of pharmacy technician job satisfaction and duties in ambulatory care pharmacy settings: A mixed-methods analysis.

PURPOSE: Expansion of pharmacy services into ambulatory care has prompted the integration of pharmacy technicians into this setting. Many models exist for technician practice in ambulatory care, and job satisfaction in these settings needs evaluation. This study assessed the job satisfaction of ambulatory care pharmacy technicians, obtained a deeper understanding of their varied roles, and examined commitment to the pharmacy technician career and their employing organization. METHODS: This study used a mixed-methods sequential explanatory design of quantitative followed by qualitative data analysis. The phases included a validated questionnaire on job satisfaction and semistructured interviews using a modified guide and findings from the quantitative data. Descriptive statistics and constant comparative analysis were used to analyze quantitative and qualitative data, and data were integrated in the discussion. RESULTS: The questionnaire was sent to 125 potential participants at 11 organizations in 8 unique states. Seventy-four technicians participated in the quantitative phase. Seventeen of these were interviewed in the qualitative phase. Interviewees represented 7 different institutions in 6 states in the Southeast, Midwest, and Western regions of the US. Both phases indicated that respondents felt a strong commitment to their organization, with 60% of respondents indicating this on the questionnaire. Reasons for this commitment were further elucidated in the qualitative phase, which indicated high satisfaction with technician autonomy, work schedules, and ability to provide important services to patients. It was also found in both phases that technician duties varied greatly among organizations, although most technicians were involved in facilitating medication access. CONCLUSION: Ambulatory care pharmacy technicians are highly satisfied with their positions and careers. Although technician roles vary within ambulatory care settings, the majority involve facilitating medication access in various ways. As these positions become more prevalent in pharmacy practice, it will be important to continue to capitalize on satisfiers and mitigate dissatisfiers to advance the profession and ultimately provide optimal patient care.

Aggregation of alpha-synuclein disrupts mitochondrial metabolism and induce mitophagy via cardiolipin externalization.

Accumulation of α-synuclein aggregates in the substantia nigra pars compacta is central in the pathophysiology of Parkinson's disease, leading to the degeneration of dopaminergic neurons and the manifestation of motor symptoms. Although several PD models mimic the pathological accumulation of α-synuclein after overexpression, they do not allow for controlling and monitoring its aggregation. We recently generated a new optogenetic tool by which we can spatiotemporally control the aggregation of α-synuclein using a light-induced protein aggregation system. Using this innovative tool, we aimed to characterize the impact of α-synuclein clustering on mitochondria, whose activity is crucial to maintain neuronal survival. We observed that aggregates of α-synuclein transiently and dynamically interact with mitochondria, leading to mitochondrial depolarization, lower ATP production, mitochondrial fragmentation and degradation via cardiolipin externalization-dependent mitophagy. Aggregation of α-synuclein also leads to lower mitochondrial content in human dopaminergic neurons and in mouse midbrain. Interestingly, overexpression of α-synuclein alone did not induce mitochondrial degradation. This work is among the first to clearly discriminate between the impact of α-synuclein overexpression and aggregation on mitochondria. This study thus represents a new framework to characterize the role of mitochondria in PD.

The transcription factor hepatocyte nuclear factor 4A acts in the intestine to promote white adipose tissue energy storage.

The transcription factor hepatocyte nuclear factor 4 A (HNF4A) controls the metabolic features of several endodermal epithelia. Both HNF4A and HNF4G are redundant in the intestine and it remains unclear whether HNF4A alone controls intestinal lipid metabolism. Here we show that intestinal HNF4A is not required for intestinal lipid metabolism per se, but unexpectedly influences whole-body energy expenditure in diet-induced obesity (DIO). Deletion of intestinal HNF4A caused mice to become DIO-resistant with a preference for fat as an energy substrate and energetic changes in association with white adipose tissue (WAT) beiging. Intestinal HNF4A is crucial for the fat-induced release of glucose-dependent insulinotropic polypeptide (GIP), while the reintroduction of a stabilized GIP analog rescues the DIO resistance phenotype of the mutant mice. Our study provides evidence that intestinal HNF4A plays a non-redundant role in whole-body lipid homeostasis and points to a non-cell-autonomous regulatory circuit for body-fat management.

Vaginal intraepithelial neoplasia (VAIN) after radiation therapy for gynecologic malignancies: a clinically recalcitrant entity.

OBJECTIVES: Vaginal dysplasia is associated with prior radiation therapy (RT) for gynecologic malignancies. We reviewed our institution's experience with VAIN in patients who were treated with radiation therapy for a gynecologic malignancy. METHODS: A retrospective review of patients treated for VAIN was performed. All cases of patients followed and treated for VAIN after radiation therapy were identified (n=10), along with a cohort of patients with VAIN who did not have radiation therapy (n=23). RESULTS: Mean follow-up after initial diagnosis of VAIN was 37.6 months (range: 12 to 72). Cytologic screening events after diagnosis of VAIN (n=105) showed that patients with prior RT were more than twice as likely to have recurrent dysplasia (OR 3.625, 95% CI=from 1.454 to 9.0376) after treatment. Of patients who recurred, the mean time to first recurrence was 12.3 months in cases and 15.3 months in controls, which was not statistically significant (p=0.31). Screening practices at our institution ranged from 3 month to 12 month intervals. 3 patients in the RT group and 1 patient in the control group developed invasive squamous cell cancer of the vagina. CONCLUSIONS: Vaginal dysplasia after radiation therapy is more refractory to treatment than dysplasia not associated with radiation therapy, more likely to recur after surgical and ablative therapy, and may also be more likely to progress to invasive cancer. These data support the need for further study to determine the optimal follow-up screening interval and whether aggressive surgical or ablative treatment stems disease progression in this clinical scenario.

Early Clinical Prediction of Independent Outdoor Functional Walking Capacity in a Prospective Cohort of Traumatic Spinal Cord Injury Patients.

OBJECTIVE: The first objective was to identify a method for early prediction of independent outdoor functional walking 1 yr after a traumatic spinal cord injury using the motor and sensory function derived from the International Standards for Neurological Classification of Spinal Cord Injury assessment during acute care. Then, the second objective was to develop a clinically relevant prediction rule that would be accurate, easy to use, and quickly calculated in clinical setting. DESIGN: A prospective cohort of 159 traumatic spinal cord injury patients was analyzed. Bivariate correlations were used to determine the assessment method of motor strength and sensory function as well as the specific dermatomes and myotomes best associated with independent outdoor functional walking 1 yr after injury. An easy-to-use clinical prediction rule was produced using a multivariable linear regression model. RESULTS: The highest motor strength for a given myotome (L3 and L5) and preserved light touch sensation (dermatome S1) were the best predictors of the outcome. The proposed prediction rule displayed a sensitivity of 84.21%, a specificity of 85.54%, and a global accuracy of 84.91% for classification. CONCLUSIONS: After an acute traumatic spinal cord injury, accurately predicting the ability to walk is challenging. The proposed clinical prediction rule aims to enhance previous work by identifying traumatic spinal cord injury patients who will reach a mobility level that fosters social participation and quality of life in the chronic period after the injury. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Revise the different motor and sensory function assessment methods used for prognostication of walking after an acute traumatic spinal cord injury; (2) Identify clinical factors that are significantly associated with functional walking 1 yr after a traumatic spinal cord injury; and (3) Accurately estimate the likelihood of reaching independent outdoor functional walking in the chronic phase after an acute traumatic spinal cord injury. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Evaluation of the Safety of Intravenous Thiamine Administration in a Large Academic Medical Center.

BACKGROUND/OBJECTIVE: Previous literature describes increased incidence of infusion-related reactions when administering thiamine doses greater than 100 mg as an intravenous (IV) push. The purpose of this evaluation was to assess the safety of administering higher doses of thiamine as IV push compared to infusion. METHODS: A single-center, retrospective review was performed from June to October 2017. Included patients were aged 18 years or older and received 1 dose of IV thiamine 200 mg or greater. Patients were divided into 2 groups: group 1 included patients who received 200-mg IV push and, group 2 included patients who received any dose greater than 200 mg. The primary objective was to quantify and compare rate of adverse reactions between the 2 groups. Institutional thiamine prescribing practices were examined. Wilcoxon Rank Sum and Fischer exact tests were performed. RESULTS: Sixty-six percent of patients were male, and the median age was 55 years (interquartile range [IQR]: 44-63). Fifty percent received 200-mg IV push, 20% received a combination of IV infusion and IV push, and 30% received IV infusion. Adverse reactions possibly due to thiamine administration occurred in 4 (2.0%) patients. One patient received 200 mg via IV infusion, while 3 received 200 mg via IV push. There was no significant difference in adverse reaction rate between IV push and IV infusion administrations (P = .640). CONCLUSION: Our results support administering thiamine doses of 200 mg or less as an IV push. Given lack of robust safety data, it is recommended to continue to dilute doses greater than 200 mg and infuse over 30 minutes.

NCOR1 Sustains Colorectal Cancer Cell Growth and Protects against Cellular Senescence.

NCOR1 is a corepressor that mediates transcriptional repression through its association with nuclear receptors and specific transcription factors. Some evidence supports a role for NCOR1 in neonatal intestinal epithelium maturation and the maintenance of epithelial integrity during experimental colitis in mice. We hypothesized that NCOR1 could control colorectal cancer cell proliferation and tumorigenicity. Conditional intestinal epithelial deletion of Ncor1 in ApcMin/+ mice resulted in a significant reduction in polyposis. RNAi targeting of NCOR1 in Caco-2/15 and HT-29 cell lines led to a reduction in cell growth, characterized by cellular senescence associated with a secretory phenotype. Tumor growth of HT-29 cells was reduced in the absence of NCOR1 in the mouse xenografts. RNA-seq transcriptome profiling of colon cancer cells confirmed the senescence phenotype in the absence of NCOR1 and predicted the occurrence of a pro-migration cellular signature in this context. SOX2, a transcription factor essential for pluripotency of embryonic stem cells, was induced under these conditions. In conclusion, depletion of NCOR1 reduced intestinal polyposis in mice and caused growth arrest, leading to senescence in human colorectal cell lines. The acquisition of a pro-metastasis signature in the absence of NCOR1 could indicate long-term potential adverse consequences of colon-cancer-induced senescence.