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Background The phytochemical mixture TriCurin (curcumin, epigallocatechin gallate (EGCG) and resveratrol) eliminates human papillomavirus (HPV) (+) cancer cells in vitro and in vivo. In this study, we further evaluate TriCurin. Methods The activity of TriCurin and its individual compounds was assayed on W12 cells, derived from a cervical precancer containing episomal and integrated HPV16 DNA, using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, microscopy and reverse transcription-polymerase chain reaction (RT-PCR), and on HeLa cells by gene expression analysis. The stability and toxicity of TriCurin microemulsion were tested in an organotypic cervical tissue model. Results TriCurin and its individual compounds inhibit the growth of W12 cells, episomal, type 1 and 2 integrants; the relative order of activity is TriCurin, EGCG, curcumin, or resveratrol. RT-PCR shows that TriCurin activates p53 and suppresses HPV16 mRNAs E1, E2, E4, E6 and E7 at 24 h in W12 cells. Gene expression analysis shows that TriCurin activates pro-apoptotic genes and represses anti-apoptotic genes in HeLa cells. TriCurin in a microemulsion is stable and non-toxic to cervical tissue. The combination of TriCurin and tanshinone IIA exhibits additional synergy against HeLa cells. Conclusions TriCurin, and the combination of TriCurin with tanshinone IIA, are effective against HPV (+) cells. The phytochemical mixture, in the microemulsion-based cream, is a promising therapeutic for the prevention and treatment of cervical cancer.

Medical societies have over the years moved away from recommending routine pelvic examinations in older, asymptomatic women above age 65. Consequently, vulvar examination is a largely neglected component of the physical examination, unless sent to a specialist for gynecological evaluation. In recognition of these recommendations, we analyzed US trends in vulvar cancer incidence, age, and stage at diagnosis, survival, and association with human papillomavirus (HPV).Cases of vulvar and cervical cancer from 1992 to 2014 were extracted from the National Cancer Institute's Surveillance, Epidemiology, and End Results and Centers for Disease Control's data on age at diagnosis, stage of disease, and HPV-association were analyzed and compared. Incidence and mortality rates were extracted and calculated.From 1992-2014, there was a 14.3% increase in vulvar cancer rates. The absolute average incidence rate was 2.25, with HPV still being seen in vulvar carcinomas in women 65 years and above. Cervical cancer mortality rates declined by 34.2%, while vulvar cancer death rates were unchanged. We show increased intervals for cervical cancer screening is associated with later stage vulvar cancer detection. The proportion of vulvar cancer cases diagnosed in women age50 steadily decreased, from 42.05% of cases in 1992-1996 to 19.75% of total cases in 2012-2015. Meanwhile, vulvar cancer cases diagnosed in women65 yo increased from 36.62% of cases in 1992-1996 to 49.82% of cases in 2012-2015.The incidence of vulvar cancer increases with age, with the median age of diagnosis 67 years, with HPV (+) tumors occurring into 70's and 80's. Though medical societies do not routinely recommend an external genital examination in women 65 years and above, we show this is a missed opportunity to improve cancer outcomes in some older females.Video Summary:http://links.lww.com/MENO/A678.

// Sumit Mukherjee 1, 3, 5, * , Priya Ranjan Debata 5, 8, * , Rahman Hussaini 5 , Kaushiki Chatterjee 2, 4 , Juliet N.E. Baidoo 1, 3 , Samay Sampat 5 , Anita Szerszen 6 , Joseph P. Navarra 7 , Jimmie Fata 2 , Elena Severinova 6, 9 , Probal Banerjee 1, 5 and Mario R. Castellanos 6 1 Department of Chemistry, The College of Staten Island (CUNY), New York, NY, USA 2 CUNY Doctoral Program in Biology, CUNY Graduate Center, New York, NY, USA 3 CUNY Doctoral Program In Biochemistry, CUNY Graduate Center, New York, NY, USA 4 Department of Biology, The College of Staten Island (CUNY), New York, NY, USA 5 Center of Developmental Neuroscience, The College of Staten Island (CUNY), New York, NY, USA 6 Division of Research, Department of Medicine, Staten Island University Hospital (Northwell Health), New York, NY, USA 7 College of Pharmacy and Health Sciences, St. John’s University, New York, NY, USA 8 Current Address: Department of Zoology North Orissa University Baripada, Mayurbhanj, Odisha, India 9 Current Address: Cell Biology and Molecular Medicine, Rutgers University, Newark, NJ, USA * These authors contributed equally to this work Correspondence to: Probal Banerjee, email: probal.banerjee@csi.cuny.edu , probalbanerjee@yahoo.com Keywords: curcumin, cervical cancer, human papillomavirus, synergism, combination index Received: May 31, 2016 Accepted: September 02, 2016 Published: March 29, 2017 ABSTRACT Curcumin (from curry) (C) is highly potent against cervical cancer cells (CCC), but poor bioavailability has limited its clinical use. Similar natural polyphenols resveratrol (from grapes) (R), and epicatechin gallate (from green tea) (E) also display activity against CCC. By treating CCC (HeLa) with C, E, or R, or combinations of these compounds, we computed combination indices and observed a strong synergism among C, E, and R at the unique molar ratio 4:1:12.5. This combination, named as TriCurin, rapidly down regulated HPV18 E6 and NF-kB expression while concomitantly inducing the tumor suppressor protein p53 in HeLa cells. In the mouse c-Ha-ras and HPV16 E6, E7-expressing TC-1 CCC, both C and TriCurin elicited suppression of E6, induction of both p53 and acetyl-p53 (activated p53), and activation of caspase-3, but the TriCurin-evoked changes were several-fold greater than that produced by curcumin (4.7-fold for E6 inhibition, and 2-fold, 6-fold, and 1.7-fold for the induction of p53, acetyl-p53, and active caspase-3, respectively). Consequently, TriCurin was more potent in killing TC-1 and HeLa cells. Intralesional TriCurin treatment of tumors generated in mice by subcutaneously implanting the TC-1 CCC caused an 80–90% decrease in tumor growth. The ability of C to eliminate HeLa cells was significantly stabilized when delivered as TriCurin than when delivered alone. Topical application of TriCurin dispersed in a cream base afforded efficient transfer of C across the skin. Subcutaneous TriCurin injection yielded no adverse effect in tumor-naive healthy mice. Thus, TriCurin is a safe and promising therapeutic agent against HPV-associated disease.

// Longzhu Piao 1, 2 , Sumit Mukherjee 3, 4 , Qing Chang 4, 5 , Xiujie Xie 1, 2 , Hong Li 6 , Mario R. Castellanos 7 , Probal Banerjee 3, 4 , Hassan Iqbal 1, 2 , Ryan Ivancic 1, 2 , Xueqian Wang 1, 2 , Theodoros N. Teknos 1, 2 and Quintin Pan 1, 2 1 Department of Otolaryngology-Head and Neck Surgery, The Ohio State University Medical Center, Columbus, Ohio, USA 2 Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA 3 Ph.D. Program in Biochemistry at the Graduate Center of the City University of New York, New York, USA 4 Department of Chemistry and Center for Developmental Neuroscience, College of Staten Island, Staten Island, New York, USA 5 Department of Pathology and Laboratory Medicine, Staten Island University Hospital, Northwell Health, Staten Island, New York, USA 6 Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA 7 Division of Research, Department of Medicine, Staten Island University Hospital, Northwell Health, Staten Island, New York, USA Correspondence to: Quintin Pan, email: Quintin.Pan@osumc.edu Keywords: human papillomavirus, p53, head and neck cancer, curcumin, catechin Received: December 22, 2015 Accepted: May 13, 2016 Published: July 16, 2016 ABSTRACT Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with about 600,000 new cases diagnosed in the last year. The incidence of human papillomavirus-positive head and neck squamous cell carcinoma (HPV-positive HNSCC) has rapidly increased over the past 30 years prompting the suggestion that an epidemic may be on the horizon. Therefore, there is a clinical need to develop alternate therapeutic strategies to manage the growing number of HPV-positive HNSCC patients. TriCurin is a composition of three food-derived polyphenols in unique stoichiometric proportions consisting of curcumin from the spice turmeric, resveratrol from red grapes, and epicatechin gallate from green tea. Cell viability, clonogenic survival, and tumorsphere formation were inhibited and significant apoptosis was induced by TriCurin in UMSCC47 and UPCI:SCC090 HPV-positive HNSCC cells. Moreover, TriCurin decreased HPV16E6 and HPV16E7 and increased p53 levels. In a pre-clinical animal model of HPV-positive HNSCC, intra-tumoral injection of TriCurin significantly inhibited tumor growth by 85.5% compared to vehicle group ( P < 0.05, n = 7). Our results demonstrate that TriCurin is a potent anti-tumor agent for HPV-positive HNSCC. Further development of TriCurin as a novel anti-cancer therapeutic to manage the HPV-positive HNSCC population is warranted.

Background Prevention of cervical cancer is based upon the accurate diagnosis and grading of cervical lesions identified during screening. The pathological classification of cervical intraepithelial neoplasia (CIN) is problematic, as it relies on subjective criteria and is known to have high interobserver variability and low reproducibility. These limitations can result in either over or under treatment of patients. Biomarkers to improve CIN diagnosis have not overcome all these challenges. Main body Here we review the use of a promising optical imaging method using eosin-based fluorescence spectroscopy. This technique is able to perform fluorescent analysis of cervical biopsies directly from hematoxylin and eosin (H&E) stained tissues. Eosin is a brominated derivative of fluorescein. Fluorescence characteristics of protein–eosin complexes can demonstrate tissue changes associated with dysplasia and cancer. In this article we review the progress made towards developing eosin-based fluorescence spectroscopy. We describe the various morphologies seen among the CIN grades with this optical method and highlight the progress made to quantitate the spectral image characteristics. Conclusion Eosin-based fluorescence spectroscopy can be used to directly examine H&E stained tissue slides. Relevant areas can be imaged and spectral analysis done to obtain objective data to identify and grade cervical lesions.

Current therapies for glioblastoma are largely palliative, involving surgical resection followed by chemotherapy and radiation therapy, which yield serious side effects and very rarely produce complete recovery. Curcumin, a food component, blocked brain tumor formation but failed to eliminate established brain tumors in vivo, probably because of its poor bioavailability. In the glioblastoma GL261 cells, it suppressed the tumor-promoting proteins NF-κB, P-Akt1, vascular endothelial growth factor, cyclin D1 and BClXL and triggered cell death. Expression of exogenous p50 and p65 subunits of NF-κB conferred partial protection on transfected GL261 cells against curcumin insult, indicating that NF-κB played a key role in protecting glioblastoma cells. To enhance delivery, we coupled curcumin to the glioblastoma-specific CD68 antibody in a releasable form. This resulted in a 120-fold increase in its efficacy to eliminate GL261 cells. A very similar dose response was also obtained with human glioblastoma lines T98G and U87MG. GL261-implanted mice receiving intratumor infusions of the curcumin-CD68 adduct followed by tail-vein injections of solubilized curcumin displayed a fourfold to fivefold reduction in brain tumor load, survived longer, and about 10% of them lived beyond 100 days. Hematoxylin-eosin staining of brain sections revealed a small scar tissue mass in the rescued mice, indicating adduct-mediated elimination of glioblastoma tumor. The tumor cells were strongly CD68+ and some cells in the tumor periphery were strongly positive for microglial Iba1, but weakly positive for CD68. This strategy of antibody targeting of curcumin to tumor comes with the promise of yielding a highly effective therapy for glioblastoma brain tumors.

The diagnosis of cervical intraepithelial neoplasia (CIN) has low interobserver reproducibility. The pathogenesis of human papillomavirus (HPV) from infection to high-grade CIN is well understood. In benign lesions, HPV-DNA is often packaged into virions, whereas malignant transformation disrupts virion assembly. It is conceivable that if cervical lesions were exposed to endonuclease digestion, HPV virions would alter nuclear susceptibility to DNA degradation. We propose that susceptibility to endonuclease digestion can serve as a simple marker to identify CIN grade. From paraffin-embedded tissue blocks, condyloma accuminata, CIN I-III, and cervical carcinoma cases were identified. Sections were placed in a bath containing DNAse I for DNA digestion. Residual DNA was stained by a Feulgen process. Endonuclease-resistant DNA (erDNA) staining was correlated to disease grade. In addition, 10 HPV (+) patients whose infection regressed and 8 whose infection progressed to CIN II or above had their initial HPV lesions stained for erDNA. erDNA was observed in 81% condylomas and 80% CIN I cases. All CIN II, III, and cancer cases were endonuclease sensitive with 100% of lesions showing no staining. Eighty percent of HPV lesions that regressed had erDNA staining, whereas 75% lesions that progressed had no erDNA staining. The spectrum of cervical disease caused by HPV has different susceptibilities to endonuclease digestion, which may aid in the diagnosis of CIN. Furthermore, in our small pilot study, erDNA status was associated with the clinical outcomes. Prospective studies are needed to confirm this observation. erDNA status is a promising novel biomarker.

This article reports a hospital's experience confronting a community crisis, stemming from local and national breast health access issues, and evaluates the subsequent effectiveness of the initiative to improve breast care service. An interdisciplinary Breast Care Facility was developed adjacent to a Community Hospital. Patients receiving breast cancer screening during the year prior to the Breast Center opening (2002) were compared with patients in subsequent years (2003-2005). Program effectiveness was evaluated by examining screening mammography volume, wait times and cancer detection rates. Screening volume increased by 29.6%. Wait times declined from 30 weeks to 3.5 weeks. Initially, patients with a suspicious screening mammography had a 2-3 week delay for diagnostic mammography and the subsequent evaluation took another 3-4 weeks. Both times improved to an average of 2-5 days. Screening cancer detection rates increased from 3.2 per 1,000, to 6.3 per 1,000. In addition, the number of cancers identified by screening increased from 40% to 58%, p = 0.002. Patient satisfaction measured by survey was over 95%, in areas of courtesy, counseling, and overall care. Our study demonstrates that a comprehensive breast center model can increase access to breast care services, improve patient satisfaction and address focal areas of shortage. Furthermore, in the years after the opening of the breast center the cancer detection rate during screening increased, an important observation that needs to be investigated with future studies.

Background Pathological classification of cervical intraepithelial neoplasia (CIN) is problematic as it relies on subjective criteria. We developed an imaging method that uses spectroscopy to assess the fluorescent intensity of cervical biopsies derived directly from hematoxylin and eosin (H&E) stained tissues. Methods Archived H&E slides were identified containing normal cervical tissue, CIN I, and CIN III cases, from a Community Hospital and an Academic Medical Center. Cases were obtained by consensus review of at least 2 senior pathologists. Images from H&E slides were captured first with bright field illumination and then with fluorescent illumination. We used a Zeiss Axio Observer Z1 microscope and an AxioVision 4.6.3-AP1 camera at excitation wavelength of 450–490 nm with emission captured at 515–565 nm. The 32-bit grayscale fluorescence images were used for image analysis. Results We reviewed 108 slides: 46 normal, 33 CIN I and 29 CIN III. Fluorescent intensity increased progressively in normal epithelial tissue as cells matured and advanced from the basal to superficial regions of the epithelium. In CIN I cases this change was less prominent as compared to normal. In high grade CIN lesions, there was a slight or no increase in fluorescent intensity. All groups examined were statistically different. Conclusion Presently, there are no markers to help in classification of CIN I-III lesions. Our imaging method may complement standard H&E pathological review and provide objective criteria to support the CIN diagnosis.

Current therapies for glioblastoma are largely palliative, involving surgical resection followed by chemotherapy and radiation therapy, which yield serious side effects and very rarely produce complete recovery. Curcumin, a food component, blocked brain tumor formation but failed to eliminate established brain tumors in vivo, probably because of its poor bioavailability. In the glioblastoma GL261 cells, it suppressed the tumor-promoting proteins NF-κB, P-Akt1, vascular endothelial growth factor, cyclin D1 and BClXL and triggered cell death. Expression of exogenous p50 and p65 subunits of NF-κB conferred partial protection on transfected GL261 cells against curcumin insult, indicating that NF-κB played a key role in protecting glioblastoma cells. To enhance delivery, we coupled curcumin to the glioblastoma-specific CD68 antibody in a releasable form. This resulted in a 120-fold increase in its efficacy to eliminate GL261 cells. A very similar dose response was also obtained with human glioblastoma lines T98G and U87MG. GL261-implanted mice receiving intratumor infusions of the curcumin-CD68 adduct followed by tail-vein injections of solubilized curcumin displayed a fourfold to fivefold reduction in brain tumor load, survived longer, and about 10% of them lived beyond 100 days. Hematoxylin-eosin staining of brain sections revealed a small scar tissue mass in the rescued mice, indicating adduct-mediated elimination of glioblastoma tumor. The tumor cells were strongly CD68+ and some cells in the tumor periphery were strongly positive for microglial Iba1, but weakly positive for CD68. This strategy of antibody targeting of curcumin to tumor comes with the promise of yielding a highly effective therapy for glioblastoma brain tumors.

Previous studies evaluating breast arterial calcifications (BAC) as a risk marker for coronary artery disease (CAD) have been limited by sample size and have yielded mixed results. Our objective was to evaluate the association of BAC and CAD.Data sources included Medline (1970-2010), the Cochrane Controlled Trials Register electronic database (1970-2010), and CINAHL (1970-2010). The search strategy included the keywords, breast artery calcification, vascular calcification on mammogram, coronary angiography, and meta-analysis. Eligible studies included female patients who had undergone coronary angiography, the gold standard for diagnosing CAD, and had screening mammograms that revealed the presence or absence of BAC. Information on eligibility criteria, baseline characteristics, results, and methodologic quality was extracted by two reviewers. Disagreements were resolved by consensus.A total of 927 patients were enrolled in the five studies. There was a 1.59 (95% confidence interval [CI] 1-21-2.09) increased odds of angiographically defined CAD in patients with BAC seen on mammography.The presence of BAC on mammography appears to increase the risk of having obstructive CAD on coronary angiography; thus, BAC may not be a benign finding.

Objective Human papillomavirus (HPV) infections remain a leading cause of mortality worldwide. In the U.S. strategies via screening and vaccination prevent HPV-associated cervical neoplasms, but consume immense healthcare costs. The spice component curcumin has potent anticancer and antiviral properties, which have been difficult to harness as a treatment, due to its poor systemic bioavailability. This project tests the possibility of developing a curcumin-based therapy for cervical cancer. Methods Using four HPV(+) cervical cancer cell lines and normal fibroblasts we first tested the selectivity and potency of curcumin in eliminating HPV(+) cells. Subsequently, we developed a curcumin-based cervical cream and tested its efficacy in eliminating apposed HPV(+) cells and also its possible side effects on the vaginal epithelium of healthy mice. Results Curcumin selectively eliminates a variety of HPV(+) cervical cancer cells (HeLa, ME-180, SiHa, and SW756), suppresses the transforming antigen E6, dramatically inhibits the expression of the pro-cancer protein epidermal growth factor receptor (EGFR), and concomitantly induces p53. Additionally, Vacurin, a uniform colloidal solution of curcumin in a clinically used amphipathic vaginal cream, eliminates apposed HeLa cells while suppressing the expression of EGFR. In mice, daily intravaginal application of Vacurin for three weeks produced no change in body weight and when the mice were sacrificed, the vaginal tract epithelium showed no Vacurin-evoked adverse effects. Conclusion We have developed a curcumin-based vaginal cream, which effectively eradicates HPV(+) cancer cells and does not affect non-cancerous tissue. Our preclinical data support a novel approach for the treatment of cervical HPV infection.

Curcumin, an important component of the culinary spice turmeric, has been shown to harbor anticancer properties against a wide range of cancer cells with minimal toxicity toward normal cells. Two general tyrosine kinase inhibitors (TKIs) sunitinib and sorafenib are currently used in treating renal cancer. Though the use of these TKIs has significantly improved survival, both elicit distressing side effects, limiting their long-term use. We tested the activity of sunitinib and sorafenib to eliminate 786-O renal cancer cells and the efficacy of curcumin to enhance this process. A four-fold decrease in the IC50 of sunitinib, from 4.5 μM to 1.2 μM, was observed in the presence of 20-μM curcumin. However, curcumin did not potentiate the activity of sorafenib. The sunitinib-curcumin (SunC) combination sharply inhibited hyperphosphorylation of the tumor suppressor protein Rb within 8 hours of SunC treatment. Although the levels of cyclin D1 did not change in 8 hours, its expression was dramatically inhibited after 24 hours of SunC exposure. Since curcumin is known to inhibit the cyclin D1-dependent G1/S-phase kinase CDK4 and the cyclin B-dependent G2/M-phase kinase CDK1 that catalyze phosphorylation-mediated inactivation of Rb, our results indicate that SunC containing a lower dose of sunitinib would be effective in restoring the tumor suppressor activity of Rb, thereby truncating cell cycle and triggering cell death. Our results submit the possibility of using SunC as an effective antitumor formulation to reduce the dose and risk of adverse effects of sunitinib.

Background Hyperglycemia is an independent predictor of adverse outcomes during hospitalization. In patients who have pneumonia, significant hyperglycemia is associated with poor outcomes. This study evaluates the interaction of the degree of hyperglycemia and complication rates stratified by age in non-critically ill patients admitted to the hospital for care of community-acquired pneumonia. Methods Retrospective review of patient records coded for pneumonia. Analysis included 501 non-critically ill patients admitted to a tertiary care hospital in New York City. Data were stratified by diabetes status, age (less than 65 and 65 and over), and fasting blood glucose (FBG) within the first 24 hours of hospitalization. Among patients with no history of diabetes, FBG was stratified as "normal" [FBG ≤100 mg/dl (5.6 mmol/l)], "mild-hyperglycemia" [101-125 mg/dl (5.7-6.9 mmol/l)], and "severe-hyperglycemia" [≥126 mg/dl (7 mmol/l)]. The diabetic group included known diabetics regardless of FBG. The Pneumonia Severity Index (PSI) was calculated for all patients. Complications rates, hospital length of stay and mortality were compared among the groups. Results In patients age 65 and older, complication rates were 16.7% in normoglycemics, 27.5% in the "mild-hyperglycemia" group, 28.6% in the "severe hyperglycemia" group, and 25.5% in those with known diabetes. The mild and severe-hyperglycemics had similar complication rates (p = 0.94). Compared to the normal group, mild and severe groups had higher rates of complications, p = 0.05 and p = 0.03, respectively. PSI tended to be higher in those over the age of 65. PSI was not significantly different when the normal, mild, severe, and known diabetes groups were compared. PSI did not predict complications for new hyperglycemia (normals' mean score 87, mild 84.7, severe 93.9, diabetics 100). Hospital mortality did not differ among groups. Length of stay was longer (p = 0.05) among mild-hyperglycemics (days = 8.4 s.e. 14.3) vs. normals (days = 6.2 s.e.6.5). Conclusion This study shows that FBS between 101-125 mg/dl (5.7-6.9 mmol/l) on hospital admission increases pneumonia complication rates among the elderly with no previous diagnosis of diabetes.

To examine, in women who underwent cardiac catheterization, whether breast arterial calcifications (BACs) seen at screening mammography correlate with coronary heart disease (CHD) seen at coronary angiography.In an institutional review board-approved, HIPAA-compliant study, 172 women (mean age, 64.29 years +/- 11.97 [standard deviation]) who underwent coronary angiography were recruited, interviewed, and assigned to two groups: those with (CHD+) and those without (CHD-) CHD. The severity and location of the CHD were considered. Their mammograms were reviewed by a breast imaging specialist who was blinded to the CHD status. Student t test, chi(2), and multiple logistic regression tests were performed as appropriate. Presence of BAC was noted and correlated with presence of CHD and presence of cardiac risk factors.There were 104 women with and 68 women without CHD. Thirty-seven (36%) women in the CHD+ group versus 20 (29%) in the CHD-group (P = .40) had BAC. The mean age of the patients with BAC, 72 years +/- 9.8, was significantly older than the mean age of the patients without BAC, 60.4 years +/- 11.1 (P.001). Therefore, subjects were divided into those younger than 65 years and those 65 years and older. No correlation existed, despite the fact that BAC was associated with some cardiac risk factors.The authors did not observe a correlation between BAC and coronary angiography-detected CHD, even when CHD severity was considered. On the basis of these results, caution should be exercised when using screening mammography-detected BAC to identify patients with CHD.

Parathyroid hormone (PTH) function as immunologic mediator has become interesting with the recent usage of PTH analogue (teriparatide) in the management of osteoporosis. Since the early 1980s, PTH receptors were found on most immunologic cells (neutrophils, B and T cells). The in vitro evaluations for a possible role of PTH as immunomodulator have shown inconsistent results mainly due to methodological heterogeneity of these studies: it used different PTH formulations (rat, bovine, and human), at different dosages and different incubating periods. In some of these studies, the lymphocytes were collected from uremic patients or animals, which renders the interpretation of the results problematic due to the effect of uremic toxins. Parathyroidectomy has been found to reverse the immunologic defect in patients with high PTH levels. Nonetheless, the clinical significance of these findings is unclear. Further studies are needed to define if PTH does have immunomodulatory effects.

Hyperglycemia is commonly noted yet undertreated among hospitalized patients. Older adults are particularly susceptible to the adverse effects of elevated glucose because of hyperglycemia-induced immune defects coupled with age-associated immune senescence. Although the American Diabetes Association (ADA) recommends maintaining fasting blood glucose (FBG) levels below 126 mg/dL and random glucose levels below 200 mg/dL in patients on general medical wards, there is limited evidence to support these targets since the recommendations are not based on randomized, controlled trials. We discuss the limitations of the current literature and present evidence from medical intensive-care studies that other glucose targets may lead to better outcomes. Furthermore, a study we conducted demonstrates that mild FBG elevations (100 to 126 mg/dL) were associated with increased morbidity among elderly patients on general medical wards. We advocate that all hospitalized patients be screened for hyperglycemia, and treatment should follow current ADA recommendations while studies are being completed to evaluate optimal targets.

Patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD) are known to develop metastatic soft-tissue calcification, secondary to hyperparathyroidism, in tissues including the breast. Such calcifications in women could pose a problem for interpretation of mammograms, since they are thought to mimic malignant lesions and interfere with differentiation of benign from malignant disease. Investigation of this issue is important to provide high-quality, accurate breast care to women with CKD or ESRD, but little evidence is so far available. In a systematic review of the literature on the types and patterns of breast calcifications, we found only three studies that examined metastatic soft-tissue calcifications of the breast. The studies did, however, confirm that women with CKD or ESRD have a higher frequency of breast calcification than women with normal kidney function. The two older studies reported that these breast calcifications are not associated with malignancy, but the later study reported a raised rate of suspicious breast calcification among women with ESRD receiving hemodialysis, leading to an increased biopsy referral rate. In this Review we discuss the strengths and limitations of the available data and whether mammography is recommended in women with CKD or ESRD.

Background: Different appearances of breast calcification on mammography can differentiate benign from malignant disease. An increased incidence of breast calcifications in dialysis patients is established, but data for morphological characteristics in renal patients, incidence of benign and malignant calcifications, and clinical consequences are limited. In this study, we compare mammograms and the workup of abnormal calcifications of women on hemodialysis with that of women with normal renal function. Methods: This is a retrospective case-control study; 45 women on hemodialysis had their screening mammograms reviewed. A control group of 86 age-matched women with normal renal function was randomly obtained for comparison. Mammograms were examined and the recommended workup was traced. Breast calcification morphological characteristics, incidence of benign versus malignant calcifications, callback rate, and biopsy recommendation rates were compared to determine whether breast calcifications in renal patients led to excessive workups. Results: Overall, breast calcifications in the renal group were statistically significantly increased compared with controls, mostly because of several benign-appearing morphological characteristics. No statistically significant difference was present between the 2 groups with respect to callback rates. However, incidences of malignancy-associated calcification and hence biopsy recommendation rate were slightly greater for the renal group. Conclusion: Renal patients have an increase in breast calcification, mostly caused by several benign calcifications. The callback rate is no greater than that in the general population. However, there is a slightly greater incidence of malignancy-associated calcifications; hence, once called back, they have a greater probability of being recommended for biopsy.

1085 Background: When compared to normal breast epithelial cells, breast cancer cells exhibit increased metabolic activity, which produces excessive intracellular hydrogen ions (H+). This increase ...

It would be useful to develop a method to rapidly identify peptide epitopes for vaccine development. We present an algorithm that can predict sequences that have a high binding activity for HLA-A2. These sequences were able to induce specific cytolytic cells from human peripheral blood lymphocytes (PBMC). A computer-assisted algorithm was constructed to predict binding activity for HLA-A2, according to anchoring amino acid combinations. The human papillomavirus (HPV) type 18 E7 oncoprotein was used to test the algorithm. Peptides predicted to bind were synthesized and binding activity was determined by using the T2 cell assay. T2 cells pulsed with HPV-18 peptides were incubated with PBMC. Cytotoxicity assays were performed. From 110 possible sequences, four peptides were found to have a high binding activity. One of these peptides was able to induce significant lysis. Using this selection process only 3.6% of the total number of possible sequences was synthesized to identify an immunogenic peptide. Our algorithm with the T2 binding assay allows a rapid method to detect peptide epitopes.

While immunosuppressive regimens improve the overall survival of renal transplant recipients, they also contribute to the long-term complications of post-transplant malignancies. Chronic immune suppression in renal transplant recipients (RTR) increases the risk of viral-associated cancers. In male RTR, human papillomavirus (HPV) is implicated in the development of penile, anal, oropharyngeal, and non-melanoma skin carcinomas. Despite the significance of this virus in RTR, there is an overall deficiency in the understanding of the natural history of HPV infection in male RTR. In the next 20 years, it is believed that cancers will be the leading cause of death in kidney transplant recipients. HPV-associated carcinomas are of particular interest since they are sexually transmitted and in theory may be preventable diseases. This commentary highlights some of the progress made in understanding how HPV is transmitted amongst couples in the general population. It also summarizes the current knowledge of HPV infection in male RTR and describes the deficiencies in published medical literature.