BACKGROUND:Post-diagnosis smoking remains prevalent among head and neck squamous cell carcinoma (HNSCC) patients. Smoking cessation may improve patient outcomes. METHODS:A prospective longitudinal cohort study (2008-2014) included 835 newly diagnosed HNSCC patients and followed up for 7 years. Participants were categorized by smoking behavior (never smokers, former smokers, quitters, continuing smokers, and intermittent smokers). The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). RESULTS:Smoking cessation after diagnosis was associated with significantly improved OS. Quitters had a 61% reduction in mortality risk compared to continuing smokers (HR: 0.39, 95% CI: 0.22, 0.69), with the greatest benefit in oral cavity cancer patients (HR: 0.28, 95% CI: 0.12, 0.65). Intermittent smokers also showed improved survival (HR: 0.50, 95% CI: 0.31, 0.79). RFS did not significantly differ based on smoking behavior. CONCLUSIONS:Smoking cessation post-diagnosis improves OS, particularly in oral cavity cancer patients, highlighting the importance of targeted smoking cessation interventions in HNSCC care.

Abstract African Americans exhibit lower survival rates from Human Papillomavirus (HPV)-induced squamous cell carcinomas in comparison to other population groups. While socioeconomic status and access to healthcare may contribute to these disparities, mounting evidence indicates that significant biological differences between diverse ancestries play a role in the severity of different cancers such as breast cancer, colorectal cancer, and squamous cell carcinomas. The purpose of the study is to investigate diagnostic and biological differences in HPV-induced squamous cell carcinomas of the oropharynx by self-reported race. The study population consists of oropharynx cases identified at the University of Michigan (non-Hispanic White) and through the Louisiana Tumor Registry (African American). A total of 52 individuals from two study sites were included in this study, 40 of whom are men, two are women and 10 are unknown. Forty-four percent (23/52) of individuals were African Americans (AA), and 46 % (19/52) were Non-Hispanic White (NHW). Formalin-fixed paraffin-embedded (FFPE) tumors from these patients were tested for p16 expression via immunohistochemistry as a proxy for HPV status. Fifty-two percent (27/52) tested negative (p16-) and 48% (25/52) tested positive (p16+). Total RNA from these samples was extracted, sequenced, and bioinformatically analyzed to test for the presence of HPV. Among AA samples, 61% were negative for both p16 and HPV RNA (p16-/RNA-), 26% were p16+/RNA-, 13% were p16+/RNA+ and none were p16-/RNA+. Among NHWs, 37% were p16-/RNA-, 16% were p16-/RNA+, 47% were p16+/RNA+ and none were p16+/RNA-. Interestingly, 6 of 20 HPV RNA- AA samples were p16+, whereas 0 of 7 HPV RNA- NHW samples were p16+. We performed data dimensionality reduction using Principal Component Analysis (PCA) implemented in the PCAtools Bioconductor package. Four groups were separated in a plot of the first two PCs, comprising, (i) all p16+/RNA+ (18/18), (ii) dominantly p16-/RNA- (6/7), (iii) p16-/RNA- mixed with p16+/RNA-, and (iv) p16-/RNA+ in the middle of all the groups and mixing with some p16+/RNA+ samples. A total of 13/17 (76%) p16-/RNA- samples in group (iii) that were mixed with p16+/RNA- samples were AA, 3 (18%) were NHW and 1 was unknown. Based on clinical data, the PCA group (iii) consisted of samples that were characterized as invasive, keratinizing, and moderately differentiated, whereas group (ii) samples were mostly clinically characterized as nonkeratinizing. A total of 13/14 AA samples that tested p16-/RNA- possessed similar clinical attributes as samples classified as p16+/RNA-, suggesting that the p16 expression via immunohistochemistry test might be classifying a significant percent of HPV-negative AA samples as positive. Taken together, these results suggest that the p16 immunohistochemistry test for oropharyngeal cancer may be overly sensitive for classifying AA oropharynx cancer samples. Clinical decisions regarding treatment for AA based on this test have the potential to negatively impact outcomes. Citation Format: Batsirai M. Mabvakure, Shiting Li, Deborah de la Caridad Delgado Herrera, William Benjamin, Lucia Martinez Cruz, Siddhi Patil, Elham Mohebbi, Gregory T. Wolf, Anju Duttargi, Christina Lefante, Mei-Chin Hsieh, Nisha J. D'Silva, Maureen Sartor, Laura Rozek. Comparison of HPV virus-induced oropharyngeal cancer by self-reported race and the potential implications on treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB137.

Annals of the New York Academy of SciencesVolume 478, Issue 1 p. 304-306 Regulation of ATP-Citrate Lyase in Rat Adipose Tissue SEETHALA RAMAKRISHNA, SEETHALA RAMAKRISHNA Department of Physiology Diabetes Research Laboratory School of Medicine State University of New York Stony Brook, New York 11794Search for more papers by this authorWILLIAM B. BENJAMIN, WILLIAM B. BENJAMIN Department of Physiology Diabetes Research Laboratory School of Medicine State University of New York Stony Brook, New York 11794Search for more papers by this author SEETHALA RAMAKRISHNA, SEETHALA RAMAKRISHNA Department of Physiology Diabetes Research Laboratory School of Medicine State University of New York Stony Brook, New York 11794Search for more papers by this authorWILLIAM B. BENJAMIN, WILLIAM B. BENJAMIN Department of Physiology Diabetes Research Laboratory School of Medicine State University of New York Stony Brook, New York 11794Search for more papers by this author First published: October 1986 https://doi.org/10.1111/j.1749-6632.1986.tb15549.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume478, Issue1Metabolic Regulation: Application of Recombinant DNA TechniquesOctober 1986Pages 304-306 RelatedInformation

This chapter describes the posttranscriptional modifications of nonhistone proteins of salivary gland cells of Sciara coprophila. The techniques useful in studying nucleoprotein metabolism of polytene chromosomes are also discussed. The early appearance of nonhistone proteins in chromosome regions that will form puffs suggests that there may be a relationship between these proteins and the “activating” stimulus. The steroid molting hormone, ecdysone, induces puff formation only at specific stages of development. Either before or at the onset of puff formation there is a substantial accumulation of pre-existing protein in and around the developing puff. There is a pool of preexisting cytoplasmic proteins that, when acted upon either directly or indirectly by a specific hormone, allows recognition by this protein(s) of specific sites on the genome. The early appearance of nonhistone proteins may be part of the biochemical mechanism for the control of chromosomal loci designated to become activated by ecdysone. As the effects of endogenous ecdysone in Sciara coprophila are permanent, the transfer of cytoplasmic proteins to the nucleus may represent a mechanism for stable differentiation.

Synthesis and transport of proteins to the cell nucleus during puff induction was studied in S. coprophila. Changes in grain distribution along chromosomes (L-methionine [35S] incorporation into protein) were correlated with puffs induced by ecdysterone in vitro; A pattern of specific labelling at the sites of incipient puffs was noted within 2 h after the addition of the hormone, i.e. grains on the chromosomes were in clusters, characteristic for this time point and not seen in the controls (where only non-specific labeling was noted 0-4 h). Characteristic chromosomal puffs appeared between 3-4 h after the addition of ecdysterone. It was concluded that during ecdysterone-induced puff formation in salivary gland chromosomes, proteins which had been previously synthesized were selectively transported from the cytoplasm to specific sites on the chromosomes.

Eu- and heterochromatin fractions prepared from normal liver and Novikoff hepatoma were tested for their capacity to direct the synthesis of RNA. Using purified RNA polymerase, template activity was measured by the incorporation of C14 GTP into RNA. Unlike DNA, chromatin fractions had increased template activity at increased salt concentrations. No difference was observed in the priming capacity of either eu- or heterochromatin fractions derived from normal liver or Novikoff hepatoma.

Side-chain modifications of the nucleoproteins are believed to be involved in the control of gene function. Rat liver nuclei and chromatin incubated in adenosine triphosphate labeled in the gamma position with phosphorus-32 demonstrated rapid phosphorylation in vitro of the nuclear proteins. Dipteran salivary glands incubated in either labeled adenosine triphosphate or ortho-phosphate labeled with phosphorus-32 showed that there is phosphorylation of chromosomal protein. The phosphorus is associated in protein from both liver and salivary gland nuclei predominantly with phosphoserine.

Lipid composition and metabolism of subcutaneous adipose tissue and lipoma of man Supplement 15. Handbook of Physiology, Adipose Tissue Alfred Gellhorn, College of Physicians and Surgeons, Columbia University, New York City, New YorkSearch for more papers by this authorWilliam Benjamin, College of Physicians and Surgeons, Columbia University, New York City, New YorkSearch for more papers by this author Alfred Gellhorn, College of Physicians and Surgeons, Columbia University, New York City, New YorkSearch for more papers by this authorWilliam Benjamin, College of Physicians and Surgeons, Columbia University, New York City, New YorkSearch for more papers by this author Published online: 1 January 2011 https://doi.org/10.1002/cphy.cp050166 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Abstract The sections in this article are: Comprehensive PhysiologyBrowse other articles of this reference work:BROWSE TABLE OF CONTENTSBROWSE BY TOPICBROWSE A-Z RelatedInformation

s1 May 1965Studies on the Mechanism of Action of Insulin in Alloxan-diabetic Rats.Alfred Gellhorn, M.D., F.A.C.P., William Benjamin, M.D.Alfred Gellhorn, M.D., F.A.C.P.Search for more papers by this author, William Benjamin, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-62-5-1078_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptInsulin has been demonstrated to produce many changes in metabolism in the normal and diabetic organism with such complex interrelationships that the fundamental site or sites of action of the hormone are not yet fully known. Evidence, however, from studies of isolated tissues as well as the intact animal have revealed specific stimulatory actions of insulin on glucose transport across certain cell membranes, intracellular glucose phosphorylation, glycogen synthetase, de novo synthesis of fatty acids from acetate, and mono-unsaturated fatty acid synthesis from saturated fatty acids. Since in most of these instances increased enzyme activity has followed the insulin administration, studies... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Alfred Gellhorn, M.D., F.A.C.P.; William Benjamin, M.D.Affiliations: New York, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAlterazioni lipidemiche nel diabete mellitoDiabetic Lipemia 1 May 1965Volume 62, Issue 5Page: 1078-1079KeywordsCell membranesEnzymesFatty acidsGlucoseGlycogensHormonesInsulinLigases ePublished: 1 December 2008 Issue Published: 1 May 1965 PDF downloadLoading ...

Adipose tissue has been found to be exquisitely responsive to changes in the physiological state of the whole organism. Thus, fatty acid oxidation, synthesis, and release, oxygen uptake and glucose utilization, are profoundly and characteristically affected by temperature (l), nutrition (2, 3), hormones (4), age (5, 6), and the genetic constitution (7). The mechanism by which each adaptation is made in metabolism by adipose tissue is poorly understood. Recent studies of lipid metabolism in adipose tissue indicate that there may be a common change in lipid biosynthesis with aging and diabetes for, in both, the rate of fatty acid synthesis (5, 8) and oxygen uptake (9, 10) is markedly decreased. It has also been shown that there is a marked decrease in the synthesis of palmitoleic and oleic acids de noso in adipose tissue from old rats compared to young, which is repaired by the administration of insulin or by the feeding of a fat-free diet (6). In this report, studies on the incorporation of acetate-1-i4C and stearic acid-l-% in vitro into the individual fatty acids of the epididymal fat pad from normal, alloxan-diabetic, and insulin-treated rats are presented. These experiments show a marked depression in the amount and synthesis of the monounsaturated fatty acids of adipose tissue from diabetic rats. This defect is not repaired by the addition of insulin in

Lipid metabolism and chemistry was studied in adipose tissues of the rat from the age of 38 days to 647 days. Aging process was characterized by a marked decrease in lipid synthesis from acetate, a reduction in the proportion of glucose metabolized by the pentose phosphate pathway, and a lower rate of palmitate incorporation into the mixed lipids. Oxidation of palmitic acid to CO2 and release of free fatty acid by epididymal fat was the same in young and old tissues under control conditions; when, however, glucose was absent from the medium or when epinephrine was added, there was a significantly greater rate of palmitic acid oxidation and free fatty acid release by young compared to old adipose tissue. Rate of acetate incorporation into mixed lipids by multiple adipose tissue sites was determined at different ages. Consistently greater rates of lipid biosynthesis were found in the epididymal, perirenal, mesenteric and interscapular adipose tissues than in subcutaneous fat at all ages. Rate of lipid synthesis by the interscapular fat (unlike any of the other depots) remained high at all ages studied. A greater proportion of short chain fatty acids was found in adipose tissues from young rats than in the old. This was related to fatty acid composition of rat milk.

Miany lines of evidence indicate that all specialized cells contain the total genetic information characteristic of the organism, but the mechanisms involved in the selective expression of this total information are unknown. Stedman and Stedman' suggested that the histones, the basic proteins of the nucleus, could serve as the controlling mechanism. Most cells of an organism, however, have the same histones,2' 3 and since the histones of individual organs such as liver and brain do not change appreciably during developments or during carcinogenesis,5' 6 it seems unlikely that the histones alone possess sufficient specificity for the control of gene function. Sypherd and Strauss7 suggested that an associated RNA species complementary to particular sequences of DNA could provide a mechanism for the histones to act as repressors by conferring additional specificity to these proteins. Huang and Bonner8 have recently described an RNA-histone complex in the pea seedling. We have concurrently carried out experiments on the nucleoprotein fraction isolated from normal rat liver nuclei and have found an RNA species with a high adenine and uridine content which is intimately associated with the nucleoprotein fraction and is resistant to ribonuclease. After extraction from the basic protein with phenol and detergent, this RNA species is RNase-sensitive and is heterogeneous by sucrose density gradient analysis. Materials and Methods.-Male Wistar rats weighing 100-120 gm from the Columbia University Colony were used in these experiments. They were fed rat pellets (A. E. Staley Manufacturing Co., Rockland Ill.) ad libitum. Labeled nucleoprotein: In the experiments to be reported, either the P3I-labeled RNA-nucleoprotein complex or the nucleoprotein labeled with C'4-lysine was used. For each preparation 2-5 animals were injected intraperitoneally with neutral isotonic solutions containing either 2 me of carrier-free p32 (Radiochemical Centre, Amersham, England) or 50 Muc lysine-UL-C4 (NuclearChicago Corp., Des Plaines, Ill.) per 100-gm rat. The animals were allowed free access to food and water at all times. Three hours following p32 administration-snd 4 hr after the injection of, lysine, liver nuclei were prepared and purified by a modification of the method of Maggio et al.9 With a Potter-Elvehjem homogenizer 9-12 gm of liver were homogenized in 3 vol of ice-cold buffer, pH 7.5, which consisted of 5 X 10-3 M Tris, 0.25 M sucrose, 5 mM MgCl2, 1 mM CaC12, and 30 mM KCl. The homogenate was filtered through cheesecloth and centrifuged at 800 X g at 00 for 10 min. The crude nuclear pellet was washed two times with buffer and was repelleted after each wash at 800 X g for 10 min. After washing, the pellet was resuspended in a small volume of similar buffer containing 2 M sucrose and then layered over additional hypertonic buffer in a centrifuge tube. The contents of the upper third of the tube were stirred to distribute the nuclear 'suspension, which was then centrifuged for 1 hr in an SW 25:1 head at 25,000 rpm in a model L2 ultracentrifuge (Beckman Instruments, Inc., Palo Alto, Calif.) at 5°. The supernatant was discarded, and the walls of the tube were cleansed of debris. The nuclear pellet was resuspended in buffer containing 0.25 M sucrose and then pelleted at 800 X g for 10 min. Following an additional wash and centrifugation, the pellet was washed twice with 0.15 M NaCl, 0.01 A! sodium citrate, pH 6.5.