Roland Pattillo

Neurobehavioral effects of low-level lead exposure in human neonates☆☆☆★

In a clinically healthy sample of 103 African American neonates maternal blood lead levels <10 micrograms/dL were related to discrete aspects of neonatal behavior but not to a priori cluster scores of the Brazelton Neonatal Behavior Assessment Scale. In statistical tests modest detrimental effects on motor control and attention were found for neonatal subjects whose mothers had slightly higher blood lead levels in the sixth and seventh prenatal months. Correlation and dose-effect trends reveal slightly poorer attention and motor control performance among neonatal offspring of mothers with higher maternal blood lead levels. These results are in agreement with those of previous studies, which have consistently reported modest statistical relationships between low-level prenatal lead exposure and neonatal behavior.

Molecular cues on obesity signals, tumor markers and endometrial cancer.

Abstract Tumor markers are important tools for early diagnosis, prognosis, therapy response and endometrial cancer monitoring. A large number of molecular and pathologic markers have been described in types I and II endometrial cancers, which has served to define the main oncogenic, epidemiological, genetic, clinical and histopathological features. Ongoing attempts to stratify biological markers of endometrial cancer are presented. However, data on changes in tumor marker profiles in obesity-related endometrial cancer are scarce. Obesity is a pandemic in Western countries that has an important impact on endometrial cancers, albeit through not very well-defined mechanisms. Although endometrial cancer is more common in Caucasian women, higher mortality is found in African Americans who also show higher incidence of obesity. Here, we describe how obesity signals (estrogen, leptin, leptin induced-molecules, Notch; cytokines and growth factors) could affect endometrial cancer. Leptin signaling and its crosstalk may be associated to the more aggressive and poor prognosis type II endometrial cancer, which affects more postmenopausal and African-American women. In this regard, studies on expression of novel molecular markers (Notch, interleukin-1 and leptin crosstalk outcome) may provide essential clues for detection, prevention, treatment and prognosis.

Type II Endometrial Cancer Overexpresses NILCO: A Preliminary Evaluation

Objective The expression of NILCO molecules (Notch, IL-1, and leptin crosstalk outcome) and the association with obesity were investigated in types I and II endometrial cancer (EmCa). Additionally, the involvement of NILCO in leptin-induced invasiveness of EmCa cells was investigated. Methods The expression of NILCO mRNAs and proteins were analyzed in EmCa from African-American (n = 29) and Chinese patients (tissue array, n = 120 cases). The role of NILCO in leptin-induced invasion of Ishikawa and An3ca EmCa cells was investigated using Notch, IL-1, and leptin signaling inhibitors. Results NILCO molecules were expressed higher in type II EmCa, regardless of ethnic background or obesity status of patients. NILCO proteins were mainly localized in the cellular membrane and cytoplasm of type II EmCa. Additionally, EmCa from obese African-American patients showed higher levels of NILCO molecules than EmCa from lean patients. Notably, leptin-induced EmCa cell invasion was abrogated by NILCO inhibitors. Conclusion Type II EmCa expressed higher NILCO molecules, which may suggest it is involved in the progression of the more aggressive EmCa phenotype. Obesity was associated with higher expression of NILCO molecules in EmCa. Leptin-induced cell invasion was dependent on NILCO. Hence, NILCO might be involved in tumor progression and could represent a new target/biomarker for type II EmCa.

Endometrial carcinoma with ectopic human chorionic gonadotropin expression

Highlights • Aggressive course and treatment resistance characterize ectopic human chorionic gonadotropin.• Recurrence of endometrial cancer with ectopic hCG was treated with brachytherapy and EMACO.• The serum hCG level can serve as a marker in tumors with ectopic hCG expression.

Biomedical research's unpaid debt: NIH's initiative to support and implement fairer competition for minority students is a welcome step to redress the exploitation of African Americans by science

Louis Agassiz, a Swiss‐born American naturalist, was a leading and influential scientist in the 19th century. He was Professor of Zoology and Geology at Harvard University, the first foreign secretary of the US National Academy of Sciences, President of the American Association for the Advancement of Science, and the founding director of Harvards Museum of Comparative Zoology. In a letter to his mother, written in 1846, he wrote: “It was in Philadelphia that I first found myself in prolonged contact with negroes; all the domestics in my hotel were men of color. I can scarcely express to you the painful impression that I received, especially since the feeling that they inspired in me is contrary to all our ideas about the confraternity of the human type and the unique origin of our species. But truth before all. Nevertheless, I experienced pity at the sight of this degraded and degenerate race, and their lot inspired compassion in me in thinking that they are really men. Nonetheless, it is impossible for me to reprocess the feeling that they are not of the same blood as us. In seeing their black faces with their thick lips and grimacing teeth, the wool on their head, their bent knees, their elongated hands, their large curved nails, and especially the livid color of the palm of their hands, I could not take my eyes off their face in order to tell them to stay far away. And when they advanced that hideous hand towards my plate in order to serve me, I wished I were able to depart in order to eat a piece of bread elsewhere, rather than dine with such service. What unhappiness for the white race—to have tied their existence so closely with that of negroes in certain countries! God preserve us …

Abstract 5044: Role of obesity in Leptin-Notch crosstalk (NILCO) in endometrial cancer from African American and Chinese women

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Introduction: Endometrial cancer is the most common gynecological malignancy of the female reproductive tract. Endometrial cancer is classified into two groups: Type I, which is estrogen dependent, and Type II, which is usually associated with endometrial atrophy and is estrogen independent. Type II is the more aggressive form with a poor prognosis and is often observed more in African American women. Obesity, characterized by high levels of leptin, is a major risk factor for endometrial cancer, which suggests that leptin may play a role in endometrial cancer pathogenesis. Over-expression of Notch, IL-1 and leptin and the signaling crosstalk (NILCO) among these pro-angiogenic factors is associated with metastasis and decreased survival rates in breast cancer patients. However, much is unknown whether this association is found in endometrial cancer. Objective: In this investigation, we aim to determine whether NILCO components are differentially expressed in Type I and Type II endometrial cancer. We hypothesize that there is a positive correlation between endometrial cancer etiology and higher BMI and NILCO expression. We further hypothesize that the correlation is more evident in Type II endometrial cancer. Methods: Expression levels of Notch1, 2, 3 & 4, Jagged-1, DLL4, Survivin, Hey2, IL-1R tI, Leptin, and Ob-R were determined via immunohistochemistry (IHC) in endometrial cancer from overweight/obese African American patients and compared to endometrial cancer tissue array from Chinese women (70 cases of carcinoma and 5 cases of non-malignant duplicated cores per case, US Biomax, Inc). Staining intensity was assigned using semi-quantitative HSCORE [∑pi (i+1), where “i” is the intensity with a value of 1, 2, or 3 (weak, moderate or strong, respectively and “pi” is the percentage of stained cells for each intensity] calculated by two independent observers in 3 different fields (100 cells/each). Western Blot and qPCR analyses of tissue lysates from cancer samples and benign surrounding tissues were also used to examine the expression levels of NILCO components.Student t-test was used to determine statistical differences between samples. Results: IHC results showed that Notch1 and 4, DLL4, Survivin, and Jagged-1 were expressed higher in Type II endometrial cancer patients. IL-1R tI was expressed higher in non-malignant compared to malignant tissue samples. Western blot and qPCR analyses further corroborated these results. Conclusion: The results support our hypothesis that obesity affects the expression of NILCO components, which could be involved in endometrial cancer progression and aggressiveness. [Partially supported by NIH/NCI 1SC1CA138658-05; NIH RR03034,1C06 RR18386, NIH/NCRR 1G12RR026250-03 and MSM/Tuskegee Univ/UAB Cancer Center Partnership grant 5U54CA118638. The National Center for Advancing Translational Sciences of the NIH Award UL1TR000454]. Citation Format: Danielle Daley-Brown, Regina Lee, Gabriela Oprea-Ilies, Emerald Screws, Roland Matthews, Roland Pattillo, Ruben Rene Gonzalez-Perez. Role of obesity in Leptin-Notch crosstalk (NILCO) in endometrial cancer from African American and Chinese women. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5044. doi:10.1158/1538-7445.AM2014-5044

Abstract 1008: Leptin-induced NILCO in endometrial cancer is linked to obesity

Background: Endometrial cancer (EmCa) Type I is estrogen dependent whereas Type II is estrogen independent and usually associated with endometrial atrophy. Type II is the more aggressive form with a poor prognosis. Obesity is a growing epidemic and is a major risk factor for EmCa. African-American women have higher incidence of obesity, and are more likely to die from EmCa even though the risk of developing EmCa is lower in Caucasian women. Obesity is characterized by high serum leptin levels, which are associated cancer incidence, metastasis and poor prognosis. Leptin9s effects in breast cancer are related to the induction of a crosstalk between Notch, IL-1 and leptin (NILCO). It is hypothesize that there is a positive correlation between Type II EmCa, NILCO and obesity. Methods: The expression of NILCO components was determined by immunohistochemistry in Type I vs Type II EmCa biopsies from obese African American and lean tissue array from Chinese patients. Additionally, the effects of leptin on cell proliferation and NILCO expression were determined in cell lines derived from Type I and Type II EmCa (Ishikawa, Hec1a, An3ca and KLE), respectively. Results: NILCO components were expressed higher in Type II EmCa, more advanced disease, and correlated with obesity. Also, leptin induction of NILCO was more prominent in Type II EmCa cells. Conclusions: Obesity signals (i.e., leptin) could induce NILCO in EmCa. Leptin could play a significant role in EmCa progression, especially in Type II EmCa. Therefore, NILCO could represent a novel biomarker for the more aggressive Type II EmCa. These observations could be more relevant for obese EmCa patients. Citation Format: Danielle Daley-Brown, Gabriela Oprea-Ilies, Kiara T. Vann, Roland Pattillo, James Lillard, Ruben Rene Gonzalez-Perez. Leptin-induced NILCO in endometrial cancer is linked to obesity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1008.

Abstract C78: NILCO: A marker for obesity-related endometrial cancer in African American women

Obesity is a pandemic in Western countries and has a significant impact on endometrial cancer (EmCa) incidence and prognosis. Although EmCa is more common in Caucasian women, higher mortality is found in African Americans who also show higher incidence of obesity. The reasons for this cancer health disparity are not completely understood. Obesity is characterized by high levels of leptin. Leptin signaling may play a key role in the progression of the more aggressive form of EmCa, Type II, which is independent from hormonal cues. We have shown that leptin induces a signaling crosstalk in breast cancer with oncogenic and angiogenic factors (NILCO: Notch, IL-1 and Leptin Crosstalk Outcome). Hence, we hypothesize that NILCO could play an important role in Type II Emca developed by obese African American women. However, no data on NILCO signaling in EmCa is currently available. Real-Time PCR, Immunohistochemistry and Western Blot analyses were used to determine whether NILCO components are differentially expressed in EmCa biopsies (Type I vs Type II EnCa) obtained from obese African American women. All tissue samples had a paired control sample from adjacent non-tumor endometrial tissue determined by pathologists. The tissue samples (n=29) were obtained from Grady Memorial Hospital, Atlanta, GA. Patient9s written informed consent was obtained for all samples collected as well as IRB approval from Morehouse School of Medicine, Atlanta, GA. In addition, commercially available EmCa tissue arrays from Chinese patients were co-examined for the expression of NILCO. Biopsy features included age, grading, and TNM staging. However, no body weight or body mass index information was available. Each array contained 150 cores, including 75 cases in duplicate. Overall, NILCO molecules were expressed higher in Type II EmCa regardless of obesity status. Notably, Type II EmCa from obese African American women showed the highest expression of NILCO. Present data suggest for the first time that NILCO could be instrumental for the development of EmCa; more specifically for obesity-related Type II EmCa, and may play a role as potential biomarkers for the disease. Citation Format: Danielle Daley-Brown, Gabriela Oprea-Ilies, Regina Lee, Kiara T. Vann, Viola Lanier, Alexander Quarshie, James Lillard, Roland Pattillo, Ruben Rene Gonzalez-Perez. NILCO: A marker for obesity-related endometrial cancer in African American women. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C78.