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Georgia

Georgia: cancer statistics (2006-10) Source: NCI State Cancer Profiles

People newly diagnosed with cancer / yr: 41,125
Age-standardised rate, incidence per 100,000 people/yr: 464.6
People dying from cancer /yr: 14,930
Mortality rate per 100,000 people/yr: 179.2

Georgia: Cancer Organizations and resources
Latest Research Publications from Georgia

Georgia: Cancer Organizations and resources (15 links)


Latest Research Publications from Georgia

Klaassen Z, Hamilton RJ
The Role of Robotic Retroperitoneal Lymph Node Dissection for Testis Cancer.
Urol Clin North Am. 2019; 46(3):409-417 [PubMed] Related Publications
Retroperitoneal lymph node dissection (RPLND) is complex; however, recent advances in technology have allowed adoption of the robotic platform for highly select cases. Initial case series have shown improved cosmesis, less blood loss, and decreased length of stay compared with open RPLND. Our preference for performing robotic RPLND is via a transperitoneal approach with the patient in the supine position, thus facilitating a bilateral template dissection identical to that used in all our open procedures. Robotic RPLND should mimic the open approach with regard to oncologic principles and should only be performed by clinicians well versed in open RPLND.

Saini G, Ogden A, McCullough LE, et al.
Disadvantaged neighborhoods and racial disparity in breast cancer outcomes: the biological link.
Cancer Causes Control. 2019; 30(7):677-686 [PubMed] Related Publications
Neighborhoods encompass complex environments comprised of unique economic, physical, and social characteristics that have a profound impact on the residing individual's health and, collectively, on the community's wellbeing. Neighborhood disadvantage (ND) is one of several factors that prominently contributes to racial breast cancer (BC) health disparities in American women. African American (AA) women develop more aggressive breast cancer features, such as triple-negative receptor status and more advanced histologic grade and tumor stage, and suffer worse clinical outcomes than European American (EA) women. While the adverse effects of neighborhood disadvantage on health, including increased risk of cancer and decreased longevity, have recently come into focus, the specific molecular mechanisms by which neighborhood disadvantage increases BC risk and worsens BC outcomes (survivorship, recurrence, mortality) are not fully elucidated. This review illuminates the probable biological links between neighborhood disadvantage and predominantly BC risk, with an emphasis on stress reactivity and inflammation, epigenetics and telomere length in response to adverse neighborhood conditions.

Gupta DR, Liu Y, Jiang R, et al.
Racial Disparities, Outcomes, and Surgical Utilization among Hispanics with Esophageal Cancer: A Surveillance, Epidemiology, and End Results Program Database Analysis.
Oncology. 2019; 97(1):49-58 [PubMed] Related Publications
BACKGROUND: Hispanic patients with esophageal cancer (EC) have racially disparate survival outcomes compared with white patients.
OBJECTIVES: We explored the impact on survival of racial differences in socioeconomic factors, tumor characteristics, and rates of surgical utilization in patients with EC.
METHOD: Using the SEER (Surveillance, Epidemiology, and End Results) registry, we identified 22,531 cases of EC in Hispanic and white patients between the ages of 18 and 65 years in 2003-2014. Of these, 6,250 cases had locoregional EC. Patients were categorized according to age, gender, education, tumor grade, histology, primary tumor site, and surgical status. Postdiagnosis survival was examined over time and compared by race and stratified by surgical status.
RESULTS: Compared with whites, Hispanics with EC had significantly higher unadjusted mortality (hazard ratio [HR] 1.11; 95% confidence interval [CI] 1.06-1.17; p < 0.001) as did Hispanics with locoregional EC (HR 1.15; 95% CI 1.03-1.29; p = 0.01). In the multivariate analysis, several socioeconomic and tumor factors were found to be independently associated with survival by race, including county of residence income and prevalence of smoking, tumor grade, stage, and primary site, and surgical utilization. After adjusting for demographic and tumor characteristics, surgical utilization in patients with locoregional EC had a significant interaction with race on overall mortality (p = 0.01). Hispanics with locoregional EC were significantly less likely to receive surgery than whites (46 vs. 60%; p < 0.001) and not receiving surgery was associated with a significantly lower overall survival (HR 2.84; 95% CI 2.65-3.04; p < 0.001).
CONCLUSIONS: A lower rate of surgery among Hispanics with potentially resectable esophageal cancer was associated with a decreased survival rate when compared to whites, even when adjusting for relevant socioeconomic and tumor factors. These data support the need to better address patient barriers to surgical treatment and the systemic biases present in medical care.

Etchie AT, Etchie TO, Shen H, et al.
Burden of disease at the same limit of exposure to airborne polycyclic aromatic hydrocarbons varies significantly across countries depending on the gap in longevity.
Ecotoxicol Environ Saf. 2019; 180:420-429 [PubMed] Related Publications
Atmospheric polycyclic aromatic hydrocarbons (PAHs) disproportionately affect human health across the globe, and differential exposure is believed to drive the unequal health burden. Therefore, this study assessed and compared the burden of disease, in disability-adjusted life years (DALYs), at the same level (or limit) of exposure to atmospheric PAHs in nine countries. We calculated the DALYs per person-year per ng/m

Gil KM, Pugh SL, Klopp AH, et al.
Expanded validation of the EPIC bowel and urinary domains for use in women with gynecologic cancer undergoing postoperative radiotherapy.
Gynecol Oncol. 2019; 154(1):183-188 [PubMed] Related Publications
OBJECTIVE: Women with endometrial or cervical cancer at risk for recurrence receive postoperative radiation therapy (RT). A patient reported outcomes (PRO) instrument to assess bowel and urinary toxicities is the Expanded Prostate Cancer Index Composite (EPIC), which has been validated in men with prostate cancer. As this instrument specifically measures bowel toxicity and the degree to which this is a problem, it was used in NRG Oncology/RTOG 1203 to compare intensity modulated RT (IMRT) to standard RT. This paper reports on the expanded validation of EPIC for use in women receiving pelvic RT.
METHODS: In addition to the EPIC bowel domain, urinary toxicity (EPIC urinary domain), patient reported bowel toxicities (PRO-CTCAE) and quality of life (Functional Assessment of Cancer Therapy (FACT)) were completed before, during and after treatment. Sensitivity, reliability and concurrent validity were assessed.
RESULTS: Mean bowel and urinary scores among 278 women enrolled were significantly worse during treatment and differed between groups. Acceptable to good reliability for bowel and urinary domain scores were obtained at all time points with the exception of one at baseline. Correlations between function and bother scores within the bowel and urinary domains were consistently stronger than those across domains. Correlations between bowel domain scores and PRO-CTCAE during treatment were stronger than those with the FACT.
CONCLUSION: Correlations within and among the instruments indicate EPIC bowel and urinary domains are measuring conceptually discrete components of health. These EPIC domains are valid, reliable and sensitive instruments to measure PRO among women undergoing pelvic radiation.

Wu L, Wu D, Ning J, et al.
Changes of N6-methyladenosine modulators promote breast cancer progression.
BMC Cancer. 2019; 19(1):326 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Breast cancer (BC) displays striking genetic, epigenetic and phenotypic diversity. N
METHODS: The expression of m6A methylases (METTL3, METTL14 and WTAP) and demethylases (FTO and ALKBH5) were analyzed by using ONCOMINE and The Cancer Genome Atlas databases and in 36 pairs of BC and adjacent non-cancerous tissue. The level of m6A in BC patients was detected by ELISA, and the function of m6A was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay and transwell assay. The database of bc-GenExMiner v4.0, Kaplan-Meier Plotter and cBioPortal were queried for correlation, mutation and prognosis analysis of BC.
RESULTS: The m6A methylases and demethylases were dysregulated in several major malignant tumors. Specifically, the expression of all m6A methylases was reduced in BC as compared with normal controls, but the demethylase ALKBH5 was induced in ONCOMINE databases and confirmed in clinical patients. METTL14 expression was positively correlated with METTL3 expression, and both showed high expression in normal breast-like and luminal-A and -B BC. Functionally, reducing m6A expression by overexpressing METTL14 and/or knockdown of ALKBH5 could inhibit breast cell viability, colony formation and cell migration. Furthermore, Kaplan-Meier, meta-analysis and univariate Cox assay showed that the expression of m6A members including METTL3, METTL14, WTAP and FTO but not their gene mutation and amplification, was tightly associated with cancer progression and poor survival.
CONCLUSIONS: Changes of m6A modulators reduced m6A may promote tumorigenesis and predict poor prognosis in BC.

Leto CJ, Sharbel D, Wang CW, et al.
Workup of Suspected Chest Metastases on
Ear Nose Throat J. 2019; 98(3):158-164 [PubMed] Related Publications
The objective of our study is to assess the impact of equivocal or positive positron emission tomography combined with low-dose noncontrast computed tomography (PET/CT) findings in the chest on treatment for head and neck cancer (HNC). We reviewed charts of patients presented at Augusta University's Head and Neck Tumor Board (AUTB) between 2013 and 2016 with the following exclusion criteria: <18 years, Veterans Affairs patients, those with incomplete data, and those without a history of head and neck squamous cell carcinoma. The lung/thorax sections of the radiologists' PET/CT reports were graded as "Positive, Equivocal, or Negative" for chest metastases. Patients who underwent workup for suspected chest metastases were assessed for treatment delays, changes in treatment plans, and complications. In addition, we evaluated the time between AUTB presentation and peri-treatment PET/CT to primary treatment initiation were calculated between groups. There was a total of 363 patients with PET/CT prior to treatment, the read was "Negative" in 71.3% (n = 259), "Equivocal" in 20.9% (n = 76), and "Positive" in 5.8% (n = 21). Of 272 patients with complete treatment data, 22 underwent workup for suspected chest metastases. Mean time from PET/CT to treatment initiation was 27.5 days without workup and 64.9 days with workup ( P < .0001), and from AUTB presentation was 29.1 days without workup and 62.5 days with workup ( P < .0001). Five (19.2%) patients experienced a complication from workup. Twenty (76.9%) patients had no changes in their treatment plan after workup. In conclusion, our results for potential chest metastases on PET/CT in patients with HNC are often not clear-cut. Workup of suspected chest metastasis based on PET/CT findings significantly delays primary treatment initiation and may cause serious complications.

Fitzsimmons AG, Dahlke DV, Bergeron CD, et al.
Impact of complementary and alternative medicine offerings on cancer patients' emotional health and ability to self-manage health conditions.
Complement Ther Med. 2019; 43:102-108 [PubMed] Related Publications
OBJECTIVES: This descriptive study investigated how cancer patient characteristics and utilization of CAM resources, services, and activities at a regional cancer center were associated with patients' understanding of their health needs, emotional health, and their ability to self-manage their condition.
DESIGN: Cross-sectional questionnaire. Sixty-one patients completed a mailed 17-item paper and pencil survey about their sociodemographics, use of CAM offerings, barriers, and perceived benefits.
SETTING: Mail-based survey completed by cancer patients in a southern state.
MAIN OUTCOME MEASURES: As a result of participating in the center's cancer support services, patients indicated if: (1) they had a better understanding of their health needs; (2) their emotional health has improved; and (3) they take better care of themselves when they are at home and in the community.
RESULTS: Participants reported using 0.93 (±1.20) CAM activities (e.g., yoga), 0.62 (±0.71) resources (e.g., the library), and 1.62 (±1.34) services (e.g., monthly support groups), although also reported experiencing 0.74 (±0.81) barriers (e.g., transportation) to accessing these offerings. Perceived benefits were interrelated, where those perceiving CAM offerings to improve their understanding of their health needs also perceived improved emotional health (χ
CONCLUSIONS: Greater utilization of CAM offerings was also associated with greater perceived benefits. These results highlight the benefits of CAM therapies for cancer patients' well-being. Integration of CAM therapies in standard cancer care should be encouraged to complement cancer treatment.

Piranlioglu R, Lee E, Ouzounova M, et al.
Primary tumor-induced immunity eradicates disseminated tumor cells in syngeneic mouse model.
Nat Commun. 2019; 10(1):1430 [PubMed] Free Access to Full Article Related Publications
Although clinically apparent metastasis is associated with late stages of cancer development, micro-metastatic dissemination may be an early event. However, the fate of these early disseminated tumor cells (DTC) remains elusive. We show that despite their capacity to disseminate into secondary organs, 4T1 tumor models develop overt metastasis while EMT6-tumor bearing mice clear DTCs shed from primary tumors as well as those introduced by intravenous (IV) injection. Following the surgical resection of primary EMT6 tumors, mice do not develop detectable metastasis and reject IV-injected tumor cells. In contrast, these cells readily grow and metastasize in immuno-deficient athymic or Rag2

Teng Y, Lang L, Shay C
ATAD3A on the Path to Cancer.
Adv Exp Med Biol. 2019; 1134:259-269 [PubMed] Related Publications
The ATPase family AAA-domain containing protein 3A (ATAD3A), a nuclear-encoded mitochondrial enzyme, is involved in diverse cellular processes, including mitochondrial dynamics, cell death and cholesterol metabolism. Overexpression and/or mutation of the ATAD3A gene have been observed in different types of cancer, associated with cancer development and progression. The dysregulated ATAD3A acts as a broker of a mitochondria-endoplasmic reticulum connection in cancer cells, and inhibition of this enzyme leads to tumor repression and enhanced sensitivity to chemotherapy and radiation. As such, ATAD3A is a promising drug target in cancer treatment.

Lang L, Chemmalakuzhy R, Shay C, Teng Y
PFKP Signaling at a Glance: An Emerging Mediator of Cancer Cell Metabolism.
Adv Exp Med Biol. 2019; 1134:243-258 [PubMed] Related Publications
Phosphofructokinase-1 (PFK-1), a rate-determining enzyme of glycolysis, is an allosteric enzyme that regulates the oxidation of glucose in cellular respiration. Glycolysis phosphofructokinase platelet (PFKP) is the platelet isoform and works as an important mediator of cell metabolism. Considering that PFKP is a crucial player in many steps of cancer initiation and metastasis, we reviewed the specificities and complexities of PFKP and its biological roles in human diseases, especially malignant tumors. The possible use of PFKP as a diagnostic marker or a drug target in the prevention or treatment of cancer is also discussed.

Booth R, Tilak AM, Mukherjee S, Daniero J
Thyroglossal duct cyst masquerading as a laryngocele.
BMJ Case Rep. 2019; 12(3) [PubMed] Related Publications
Thyroglossal duct cysts (TGDCs) are the most common congenital neck mass and often present in the paediatric population as a painless mass in the midline. A lateralised neck mass presenting for the first time in an adult may raise more concern for malignancy or a laryngocele. A 50-year-old man presented with an asymptomatic right level II neck mass adjacent to the thyroid cartilage. Preoperative CT revealed a cystic mass right of the midline with an intralaryngeal component. Intraoperatively, the lesion tracked towards the central hyoid bone; a Sistrunk procedure was performed. Postoperative pathology revealed a small foci of thyroid tissue within the mass. Careful consideration of the origin of this unusually presenting TGDC enabled appropriate operative management.

Cao Y, Trillo-Tinoco J, Sierra RA, et al.
ER stress-induced mediator C/EBP homologous protein thwarts effector T cell activity in tumors through T-bet repression.
Nat Commun. 2019; 10(1):1280 [PubMed] Free Access to Full Article Related Publications
Understanding the intrinsic mediators that render CD8

Xiong Y, He L, Shay C, et al.
Nck-associated protein 1 associates with HSP90 to drive metastasis in human non-small-cell lung cancer.
J Exp Clin Cancer Res. 2019; 38(1):122 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Metastatic lung cancer is a life-threatening condition that develops when cancer in another area of the body metastasizes, or spreads, to the lung. Despite advances in our understanding of primary lung oncogenesis, the biological basis driving the progression from primary to metastatic lung cancer remains poorly characterized.
METHODS: Genetic knockdown of the particular genes in cancer cells were achieved by lentiviral-mediated interference. Invasion potential was determined by Matrigel and three-dimensional invasion. The secretion of matrix metalloproteinase 2 (MMP2) and MMP9 were measured by ELISA. Protein levels were assessed by Western blotting and immunohistochemistry. Protein-protein interactions were determined by immunoprecipitation. An experimental mouse model was generated to investigate the gene regulation in tumor growth and metastasis.
RESULTS: Nck-associated protein 1 (NAP1/NCKAP1) is highly expressed in primary non-small-cell lung cancer (NSCLC) when compared with adjacent normal lung tissues, and its expression levels are strongly associated with the histologic tumor grade, metastasis and poor survival rate of NSCLC patients. Overexpression of NAP1 in lowly invasive NSCLC cells enhances MMP9 secretion and invasion potential, whereas NAP1 silencing in highly invasive NSCLC cells produces opposing effects in comparison. Mechanistic studies further reveal that the binding of NAP1 to the cellular chaperone heat shock protein 90 (HSP90) is required for its protein stabilization, and NAP1 plays an essential role in HSP90-mediated invasion and metastasis by provoking MMP9 activation and the epithelial-to-mesenchymal transition in NSCLC cells.
CONCLUSIONS: Our insights demonstrate the importance and functional regulation of the HSP90-NAP1 protein complex in cancer metastatic signaling, which spur new avenues to target this interaction as a novel approach to block NSCLC metastasis.

Rida P, Syed MI, Aneja R
Time will tell: Circadian clock dysregulation in triple negative breast cancer.
Front Biosci (Schol Ed). 2019; 11:178-192 [PubMed] Related Publications
Growing evidence now links circadian disruption (CD) to increased risk of developing multiple types of cancer, including breast cancer (BC). In the US, African-American (AA) BC patients have a higher mortality rate than European-Americans (EAs) with BC, and a prime suspect in this racially disparate burden has been the greater incidence of an aggressive and highly heterogeneous BC subtype called triple-negative BC (TNBC), among AAs. AAs are also more prone to CD as larger proportions of AAs engage in night shift work than EAs, and the chronotype of AAs makes it harder for them to adapt to CD than EAs. Although clock gene dysregulation has been shown to perturb transactivation of key cell cycle and apoptosis regulators, little is known about how clock gene mis-expression affects TNBC outcomes. This review examines the prognostic value of clock genes in TNBC, and evaluates patterns of clock gene dysregulation in the individual TNBC molecular subtypes. Better understanding of how CD contributes to TNBC biology may illuminate new paths to improving disease outcomes and reducing BC-related racial disparities.

Wright N, Akinyemiju T, Subhedar P, et al.
Targeting risk factors for reducing the racially disparate burden in breast cancer.
Front Biosci (Schol Ed). 2019; 11:136-160 [PubMed] Related Publications
African-American (AA) women are more likely to die from breast cancer (BC), at any age, compared to European-American women. Although breakthroughs in pre-clinical studies have resulted in potentially actionable targets in AA BC, drugs that were rationally designed for these targets have performed poorly in clinical trials. Challenges with interpatient and intratumoral heterogeneity, lack of drug sensitivity and specificity, suboptimal biomarker cut-offs, lack of drug response predictive biomarkers, drug side effects, high costs of drug development, and under-representation of AAs in clinical trials complicate the development of targeted therapies for AA BC patients. Accumulating evidence suggests that racial disparities exist in non-genetic risk factors that can alter genetic and epigenetic programs to promote breast tumorigenesis. Herein, we present a "roadmap" that addresses non-genetic risk factors that are suspected to contribute to the racial disparity in BC mortality. Increased targeting of these non-genetic risk factors may proffer a safer and more economical route to alleviating the racially disparate burden in BC.

Garlapati C, Joshi S, Sahoo B, et al.
The persisting puzzle of racial disparity in triple negative breast cancer: looking through a new lens.
Front Biosci (Schol Ed). 2019; 11:75-88 [PubMed] Related Publications
Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen and progesterone receptors and absence of amplification of human epidermal growth factor receptor (HER2). This disease has no approved treatment with a poor prognosis particularly in African-American (AA) as compared to European-American (EA) patients. Gene ontology analysis showed specific gene pathways that are differentially regulated and gene signatures that are differentially expressed in AA as compared to EA. Such differences might underlie the basis for the aggressive nature and poor prognosis of TNBC in AA patients. In-depth studies of these pathways and differential genetic signature might give significant clues to improve our understanding of tumor biology associated with AA TNBC to advance the prognosis and survival rates. Along with gene ontology analysis, we suggest that post-translational modifications (PTM) could also play a crucial role in the dismal survival rate of AA TNBC patients. Further investigations are necessary to explore this terrain of PTMs to identify the racially disparate burden in TNBC.

Zhao Z, Jordan S, Tse ZTH
Devices for image-guided lung interventions: State-of-the-art review.
Proc Inst Mech Eng H. 2019; 233(4):444-463 [PubMed] Related Publications
Lung cancer is the leading cause of cancer-related death. According to the American Cancer Society, there were an estimated 222,500 new cases of lung cancer and 155,870 deaths from lung cancer in the United States in 2017. Accurate localization in lung interventions is one of the keys to reducing the death rate from lung cancer. In this study, a total of 217 publications from 2006 to 2017 about designs of medical devices for localization in lung interventions were screened, shortlisted, and categorized by localization principle and reviewed for functionality. Each study was analyzed for engineering characteristics and clinical significance. Research regarding interventional imaging equipment, navigation systems, and surgical devices was reviewed, and both research prototypes and commercial products were discussed. Finally, the future directions and existing challenges were summarized, including real-time intra-procedure guidance, accuracy of localization, clinical application, clinical adoptability, and clinical regulatory issues.

Fabelo H, Halicek M, Ortega S, et al.
Deep Learning-Based Framework for
Sensors (Basel). 2019; 19(4) [PubMed] Free Access to Full Article Related Publications
The main goal of brain cancer surgery is to perform an accurate resection of the tumor, preserving as much normal brain tissue as possible for the patient. The development of a non-contact and label-free method to provide reliable support for tumor resection in real-time during neurosurgical procedures is a current clinical need. Hyperspectral imaging is a non-contact, non-ionizing, and label-free imaging modality that can assist surgeons during this challenging task without using any contrast agent. In this work, we present a deep learning-based framework for processing hyperspectral images of

Wu L, Zhang D, Zhou L, et al.
FUN14 domain-containing 1 promotes breast cancer proliferation and migration by activating calcium-NFATC1-BMI1 axis.
EBioMedicine. 2019; 41:384-394 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: FUN14 domain-containing 1 (FUNDC1), as a novel member of mitochondria-associated endoplasmic reticulum (ER) membranes associates with mitochondrial division and mitophagy. However, the expression profile and functional roles of FUNDC1 remain largely unclear in human cancer biology, including breast cancer (BC).
METHODS: Immunohistochemistry and western blot analysis were used to determine the expression of FUNDC1 and BMI1 polycomb ring finger oncogene (BMI1). CCK8, cell counting and transwell assays were used to analyze cell proliferation, migration and invasion, respectively. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were used to detect the transcriptional regulation of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1). The prognostic merit of NFATC1 expression was assessed by Kaplan-Meier assay.
FINDINGS: Immunohistochemistry revealed strong immunostaining for FUNDC1 in cytoplasmic and nuclear membrane distribution in BC tissues as compared with normal breast epithelium. Kaplan-Meier survival analysis showed worse outcome for BC patients with high FUNDC1 expression. In vitro assay of gain- and loss-of-function of FUNDC1 suggested that FUNDC1 could stimulate BC cell proliferation, migration and invasion. Furthermore, elevated FUNDC1 level promoted Ca
INTERPRETATION: FUNDC1 might promote BC progression by activating the Ca

Coughlin SS, Dean LT
Cancer survivorship care plans, financial toxicity, and financial planning alleviating financial distress among cancer survivors.
Support Care Cancer. 2019; 27(6):1969-1971 [PubMed] Related Publications
Concomitant with the increasing use of cancer care plans has been an increasing awareness of the potential for oncology care to result in long-term financial burdens and financial toxicity. Cancer survivors can benefit from information on support and resources to help them navigate the challenges after acute cancer treatment. While cancer survivorship plans could be a vehicle for patients to receive information on how to mitigate financial toxicity, cancer survivorship plans have typically not dealt with the financial impact of cancer treatment or follow-up care. Embedding information into cancer survivorship plans on how to reduce or avoid financial toxicity presents an opportunity to address a highly prevalent patient need. Patient-centered qualitative studies are needed to assess the type, format, and level of detail of the information provided.

He L, Gao L, Shay C, et al.
Histone deacetylase inhibitors suppress aggressiveness of head and neck squamous cell carcinoma via histone acetylation-independent blockade of the EGFR-Arf1 axis.
J Exp Clin Cancer Res. 2019; 38(1):84 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: A promising arsenal of histone deacetylase (HDAC)-targeted treatment has emerged in the past decade, as the abnormal targeting or retention of HDACs to DNA regulatory regions often occurs in many cancers. Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive malignancies worldwide associated with poor overall survival in late-stage patients. HDAC inhibitors have great potential to treat this devastating disease; however, few has been studied regarding the beneficial role of HDAC inhibition in anti-HNSCC therapy and the underlying molecular mechanisms remain elusive.
METHODS: Cell migration and invasion were examined by wound closure and Transwell assays. Protein levels and interactions were assessed by Western blotting and immunoprecipitation. HDAC activity was measured with the fluorometric HDAC Activity Assay. Phospho-receptor tyrosine kinase (RTK) profiling was determined by the Proteome Profiler Human Phospho-RTK Array.
RESULTS: ADP-ribosylation factor 1 (Arf1), a small GTPase coordinating vesicle-mediated intracellular trafficking, can be inactivated by HDAC inhibitors through histone acetylation-independent degradation of epidermal growth factor receptor (EGFR) in HNSCC cells. Mechanistically, high levels of Arf1 activity are maintained by binding to phosphorylated EGFR which is localized on HNSCC cell plasma membrane. Decreased EGFR phosphorylation is associated with reduced EGFR protein levels in the presence of TSA, which inactivates Arf1 and eventually inhibits invasion in HNSCC cells.
CONCLUSIONS: Our insights explore the critical role of EGFR-Arf1 complex in driving HNSCC progression, and demonstrate the selective action of HDAC inhibitors on this specific axis for suppressing HNSCC invasion. This novel finding represents the first example of modulating the EGFR-Arf1 complex in HNSCC by small molecule agents.

Eltelety AM, Terris DJ
Neck Dissection in the Surgical Treatment of Thyroid Cancer.
Endocrinol Metab Clin North Am. 2019; 48(1):143-151 [PubMed] Related Publications
The incidence of thyroid cancer is increasing, largely attributable to overdetection related to prevalent diagnostic and radiologic imaging modalities. Papillary thyroid cancer remains the most common thyroid malignancy. It has a high tendency for regional metastasis to the cervical lymph nodes. The optimal management of the neck in patients with thyroid carcinoma has long been an important topic of debate. This article addresses central and lateral neck dissection, providing a simplified guide to the most up-to-date and evidence-based practices.

Salarian M, Xue S, Ibhagui OY, Yang JJ
Designing Calcium-Binding Proteins for Molecular MR Imaging.
Methods Mol Biol. 2019; 1929:111-125 [PubMed] Article available free on PMC after 01/01/2020 Related Publications
Early diagnosis, noninvasive detection, and staging of various diseases, remain one of the major clinical barriers to effective medical treatment and prevention of disease progression toward major clinical consequences. Molecular imaging technologies play an indispensable role in the clinical field in overcoming these major barriers. The increasing application of imaging techniques and agents in early detection of different diseases such as cancer has resulted in improved treatment response and clinical patient management. In this chapter we will first introduce criteria for the design and engineering of calcium-binding protein (CaBP) parvalbumin as a protein Gd-MRI contrast agent (ProCA) with unprecedented metal selectivity for Gd

Griffin K, Csizmadi I, Howard LE, et al.
First-year weight loss with androgen-deprivation therapy increases risks of prostate cancer progression and prostate cancer-specific mortality: results from SEARCH.
Cancer Causes Control. 2019; 30(3):259-269 [PubMed] Article available free on PMC after 01/03/2020 Related Publications
PURPOSE: We aimed to study the associations between androgen-deprivation therapy (ADT)-induced weight changes and prostate cancer (PC) progression and mortality in men who had undergone radical prostatectomy (RP).
METHODS: Data from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort were used to study the associations between weight change approximately 1-year post-ADT initiation and metastases, castration-resistant prostate cancer (CRPC), all-cause mortality (ACM), and PC-specific mortality (PCSM) in 357 patients who had undergone RP between 1988 and 2014. We estimated hazard ratios (HR) and 95% confidence intervals (95% CI) using covariate-adjusted Cox regression models for associations between weight loss, and weight gains of 2.3 kg or more, and PC progression and mortality post-ADT.
RESULTS: During a median (IQR) follow-up of 81 (46-119) months, 55 men were diagnosed with metastases, 61 with CRPC, 36 died of PC, and 122 died of any cause. In multivariable analysis, weight loss was associated with increases in risks of metastases (HR 3.13; 95% CI 1.40-6.97), PCSM (HR 4.73; 95% CI 1.59-14.0), and ACM (HR 2.16; 95% CI 1.25-3.74) compared with mild weight gains of ≤ 2.2. Results were slightly attenuated but remained statistically significant in analyses that accounted for competing risks of non-PC death. Estimates for the associations between weight gains of ≥ 2.3 kg and metastases (HR 1.58; 95% CI 0.73-3.42), CRPC (HR 1.33; 95% CI 0.66-2.66), and PCSM (HR 2.44; 95% CI 0.84-7.11) were elevated, but not statistically significant.
CONCLUSIONS: Our results suggest that weight loss following ADT initiation in men who have undergone RP is a poor prognostic sign. If confirmed in future studies, testing ways to mitigate weight loss post-ADT may be warranted.

Abdelfatah MM, Barakat M, Ahmad D, et al.
Long-term outcomes of endoscopic submucosal dissection versus surgery in early gastric cancer: a systematic review and meta-analysis.
Eur J Gastroenterol Hepatol. 2019; 31(4):418-424 [PubMed] Related Publications
Endoscopic submucosal dissection (ESD) and gastrectomy with lymph node dissection are considered acceptable treatment modalities for early gastric cancer (EGC). In the last decade, ESD has become more favorable than surgery as it offers faster recovery, lower costs, and a superior quality of life when compared to gastrectomy. The aim of this study is to compare the long-term outcome of ESD versus surgery in EGC. We performed a systematic and comprehensive search of major reference databases (Medline, Embase, CINHAL) for all studies that compared the outcome of EGC for patients underwent ESD or surgery in the same cohort. A systematic review was conducted through November 2017, using pooled analysis to calculate 5-year overall survival (OS) rate, disease-specific survival (DSS) rate, disease-free survival (DFS) rate, and recurrence-free survival (RFS) rate of ESD versus gastrectomy. Five-year OS and DSS were similar between ESD and gastrectomy groups 96 versus 96% and 99.4 versus 99.2%, respectively. Likewise, DFS was similar in both groups 95.9 versus 98.5% odds ratio 1.86 (0.57-6.0) P=0.3. However, ESD had a lower RFS compared to surgery 92.4 versus 98.3% odds ratio 0.17 (0.1-4.9) P=0.001. Overall, there was a higher recurrence rate in patients who underwent ESD compared to surgery [40/2943 (1.4%) vs. 12/3116 (0.4) risk ratio (RR) 2.5 (1.3-4.8) P=0.005]. Moreover, synchronous and metachronous cancers were more prevalent in the ESD group compared to the surgery group [1.5 vs. 0.1% RR 5.7 (1.5-21.9) P=0.01] [16/1082 (1.5%) vs. 1/1485 (0.1%) RR 10.1 (5.9-17.1) P=0.0001]. Five-year OS, DSS and DFS were similar between ESD and surgery groups. However, recurrent, synchronous and metachronous cancers were more prevalent in patients treated by ESD compared to patients treated by surgery, resulting in a lower RFS. Adequate surveillance with upper endoscopy is crucial after ESD to detect early recurrence and metachronous lesions.

Grunwell JR, Long LD, Bryan LN, et al.
Factors affecting same-day cancelation of outpatient pediatric oncologic procedural sedation.
Pediatr Hematol Oncol. 2018 Aug - Sep; 35(5-6):309-315 [PubMed] Related Publications
BACKGROUND: Children with cancer undergo serial invasive, painful procedures as a part of their diagnosis, treatment, and surveillance regimens that require procedural sedation (PS). Some may have a delay in their treatment plan due to same-day cancelation (SDC) of the procedure due to issues related to sedation or other factors. The objective of this report was to evaluate the factors resulting in the SDC of hematology and oncology patients in an outpatient pediatric sedation service.
METHODS: Retrospective review of children with cancer or other hematologic disorders undergoing outpatient procedures using a dedicated pediatric sedation team from January 2012 to December 2017. The children with SDC were compared to controls (ie, patients not canceled) during the above study period.
RESULTS: A total of 100 patients had SDC during the study. The median age was 10 years (25th percentile to 75th percentile: 7-10 years). The overall SDC rate was 3% and 78/100 (78%) had acute lymphoblastic leukemia. Most common procedure was lumbar puncture with intrathecal chemotherapy in 82/100 (82%) patients. Inadequate blood counts, acute illness, and not nil per os (NPO) accounted for 83% of the reasons for SDC. Type of health insurance, estimated household income, or distance traveled to the clinic did not impact SDC.
CONCLUSIONS: The most common factors for SDC included inadequate blood counts, acute illness, and not meeting NPO guidelines. Understanding factors affecting SDC may help improve the efficiency of time-sensitive care delivered to children with cancer and other hematologic concerns by a pediatric sedation service.

Ntumy M, Maya E, Lizneva D, et al.
The pressing need for standardization in epidemiologic studies of PCOS across the globe.
Gynecol Endocrinol. 2019; 35(1):1-3 [PubMed] Related Publications
The polycystic ovary syndrome (PCOS) is a common and important complex endocrine metabolic disorder affecting women mainly in the reproductive age. The prevalence of the disorder varies depending on the epidemiologic design and criterion used to study the disease. This variation in methodology and subsequent effect on epidemiologic estimate makes it difficult to compare prevalences and phenotypes across geographical areas and assess the effect of cultural and racial variations on PCOS phenotypes. Overall, there is an urgent need for a globally accepted standardized protocol for epidemiologic studies of PCOS, which will maximize the comparability of studies around the globe. To address this issue the Androgen Excess and PCOS Society, Inc. has designated an expert Task Force to draft recommendations to guide epidemiologic research worldwide. Once completed, the use of such recommendations will enable epidemiologists to the effects of geographical and cultural variations of PCOS prevalence and assist in determining the phenotype-genotype associations in the disorder. Further, it will assist in developing informed, and thus effective, public health policy. In essence, the need to standardize epidemiologic studies across the globe is pressing and urgent.

Kautiainen RJ, Na SD, King TZ
Neurological predictor scale is associated with academic achievement outcomes in long-term survivors of childhood brain tumors.
J Neurooncol. 2019; 142(1):193-201 [PubMed] Related Publications
INTRODUCTION: Survivors of childhood brain tumors exhibit impairments in academic performance and have lower rates of educational attainment compared to healthy same-aged peers. Prior research has demonstrated the concurrent validity of the Neurological Predictor Scale (NPS), a measure that incorporates tumor-related treatments and complications into one cumulative score, in predicting IQ, adaptive functioning, and core neurocognitive skills. The purpose of this study is to determine whether the NPS predicts academic achievement outcomes over and above the effects of individual treatment factors alone.
METHODS: Sixty-two adult survivors completed four untimed measures of academic achievement from the Woodcock-Johnson III.
RESULTS: NPS scores significantly predicted performance on all four academic measures: Letter Word ID (R
CONCLUSION: This study extends prior research by demonstrating that the NPS is significantly associated with academic achievement in survivors on average 15.9 years after diagnosis. The NPS may be especially helpful in clinical research when studies lack the statistical power to investigate how treatments and neurological conditions individually contribute to outcomes.

Hayes NS, Hohman K, Vinson C, Pratt-Chapman M
Comprehensive cancer control in the U.S.: summarizing twenty years of progress and looking ahead.
Cancer Causes Control. 2018; 29(12):1305-1309 [PubMed] Article available free on PMC after 19/12/2019 Related Publications
In order to celebrate the accomplishments of the Centers for Disease Control and Prevention's (CDC) National Comprehensive Cancer Control Program (NCCCP), the Comprehensive Cancer Control National Partners (CCCNP) developed this Special Issue on Cancer Causes and Control. This, the third Special Issue on Comprehensive Cancer Control (CCC), is a reflection of 20 years of building successful partnerships to prevent and control cancer; planning and implementing strategic cancer control; collaborating to address national cancer prevention and control priorities; evaluating efforts; sharing successes; and, in later years, serving as a model for global cancer control planning and implementation. The CDC currently supports cancer control planning and implementation in all 50 states, the District of Columbia, eight tribes or tribal organizations, and seven Pacific Island Jurisdictions and U.S. territories through the NCCCP. CCC is an approach that brings together multi-sector partners to address the cancer burden in a community collectively by leveraging existing resources and identifying and addressing cancer related issues and needs. The Comprehensive Cancer Control National Partnership (CCCNP), a partnership of national organizations, has been committed to supporting comprehensive cancer control efforts since 1999. We summarize the efforts described in this Special Issue. We also describe opportunities and critical elements to continue the momentum for comprehensive cancer control well into the future.

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