Impact of Nanomedicine in Women's Metastatic Breast Cancer.

Metastatic breast cancer is responsible for 90% of mortalities among women suffering from various types of breast cancers. Traditional cancer treatments such as chemotherapy and radiation therapy can cause significant side effects and may not be effective in many cases. However, recent advances in nanomedicine have shown great promise in the treatment of metastatic breast cancer. For example, nanomedicine demonstrated robust capacity in detection of metastatic cancers at early stages (i.e., before the metastatic cells leave the initial tumor site), which gives clinicians a timely option to change their treatment process (for example, instead of endocrine therapy they may use chemotherapy). Here recent advances in nanomedicine technology in the identification and treatment of metastatic breast cancers are reviewed.

Excising Additional Margins at Initial Breast-Conserving Surgery (BCS) Reduces the Need for Re-excision in a Predominantly African American Population: A Report of a Randomized Prospective Study in a Public Hospital.

BACKGROUND: Margin status is an important prognostic factor for local recurrence after breast conserving surgery (BCS) for breast cancer. We designed a prospective randomized trial to evaluate the effect of shave margins on positive margins and locoregional recurrence (LRR). METHODS: Patients were randomized to BCS or BCS with resection of 5 additional margins (BCS + M). Tumor margins were classified as negative [>2 mm for ductal carcinoma in situ (DCIS); >1 mm for invasive carcinoma] based on guidelines at the time of accrual. RESULTS: A total of 75 patients with stage 0-III breast cancer (76 samples) were randomized, mean age 59.6 years with median follow-up 39.5 months. Overall, 21 patients (27.6 %) had positive margins: 14 had undergone BCS and 7 BCS + M (p = 0.005). Of the 21 patients with positive margins, 19 had DCIS on final pathology (OR 7.56; 95 % CI 1.52-37.51).All patients with positive margins were offered re-excision; 11 had negative final margins after re-excision surgery. Overall, 6 patients (8.3 %) developed LRR with recurrence being more common in the BCS group when compared with the BCS + M group (17.2 vs 2.3 %; p = 0.025). CONCLUSIONS: Taking additional cavity shave margins at the time of initial excision resulted in a reduction in positive margin rate, a decrease in return to operating room for re-excision, and lower LRR.

The Dilemma of Breast Cancer Treatment and Existing Collagen Vascular Disease: A Case of Scleroderma and Review of the Literature.

Collagen vascular diseases present a treatment dilemma for patients with breast cancer. Due to the potential for severe, acute, and late complications of radiation therapy, a history of collagen vascular disease (CVD) is a relative contraindication to breast-conserving treatment. We present a case of early stage breast cancer in a patient with severe scleroderma treated with breast-conserving surgery without radiation and a brief review of the published literature regarding the therapeutic approach to the patient with CVD and breast cancer.

Nanomagnetic levitation three-dimensional cultures of breast and colorectal cancers.

BACKGROUND: Innovative technologies for drug discovery and development, cancer models, stem cell research, tissue engineering, and drug testing in various cell-based platforms require an application similar to the in vivo system. MATERIALS AND METHODS: We developed for the first time nanomagnetically levitated three-dimensional (3-D) cultures of breast cancer (BC) and colorectal cancer (CRC) cells using carbon-encapsulated cobalt magnetic nanoparticles. BC and CRC xenografts grown in severe combined immunodeficient (SCID) mice were evaluated for N-cadherin and epidermal growth factor receptor expressions. These phenotypes were compared with two-dimensional and 3-D cultures grown in a gel matrix. RESULTS: The BC and CRC cells grown by magnetic levitation formed microtissues. The levitated cultures had high viability and were maintained in culture for long periods of time. It has been observed that N-cadherin and epidermal growth factor receptor activities were highly expressed in the levitated 3-D tumor spheres and xenografts of CRC and BC cells. CONCLUSIONS: Nanomagnetically levitated 3-D cultures tend to form stable microtissues of BC and CRC and maybe more feasible for a range of applications in drug discovery or regenerative medicine.

Case Report: A challenging diagnosis of an apocrine sweat gland carcinoma.

The differential diagnosis for an axillary mass in a patient with a previously treated malignancy is broad and definitive tissue diagnosis is required to guide treatment and surveillance strategies. We present the case of a 76-year-old African American male with a history of prostate cancer who presented with a left axillary mass two years after achieving remission from his prostate malignancy. Due to the diagnostic challenge, this excisional biopsy was reviewed at four different academic centers. Although no universal consensus among these institutions' pathologists, but in the context of clinical presentation and anatomic location, the overall clinical findings are consistent with apocrine sweat gland carcinoma. The mass was treated with complete local surgical excision, though regional lymph node metastasis occurred 2 years later. Multimodal treatment with surgery and radiation was done with removal of regional metastasis and no distant disease was identified. Primary apocrine carcinoma is a rare cutaneous neoplasm with less than 100 reported cases in the literature. A combination of clinical history and presentation, histomorphology, anatomical location, and immunohistochemistry is used to support the diagnosis and ultimately drive management.

Active Targeting Hyaluronan Conjugated Nanoprobe for Magnetic Particle Imaging and Near-Infrared Fluorescence Imaging of Breast Cancer and Lung Metastasis.

A major contributing cause to breast cancer related death is metastasis. Moreover, breast cancer metastasis often shows little symptoms until a large area of the organs is occupied by metastatic cancer cells. Breast cancer multimodal imaging is attractive since it integrates advantages from several modalities, enabling more accurate cancer detection. Glycoprotein CD44 is overexpressed on most breast cancer cells and is the primary cell surface receptor for hyaluronan (HA). To facilitate breast cancer diagnosis, we report an indocyanine green (ICG) and HA conjugated iron oxide nanoparticle (NP-ICG-HA), which enabled active targeting to breast cancer by HA-CD44 interaction and detected metastasis with magnetic particle imaging (MPI) and near-infrared fluorescence imaging (NIR-FI). When evaluated in a transgenic breast cancer mouse model, NP-ICG-HA enabled the detection of multiple breast tumors in MPI and NIR-FI, providing more comprehensive images and a diagnosis of breast cancer. Furthermore, NP-ICG-HAs were evaluated in a lung metastasis model. Upon NP-ICG-HA administration, MPI showed clear signals in the lungs, indicating the tumor sites. This is the first time that HA-based NPs have enabled MPI of cancer. NP-ICG-HAs are an attractive platform for noninvasive detection of primary breast cancer and lung metastasis.

Recurrent and convolutional neural networks for sequential multispectral optoacoustic tomography (MSOT) imaging.

Multispectral optoacoustic tomography (MSOT) is a beneficial technique for diagnosing and analyzing biological samples since it provides meticulous details in anatomy and physiology. However, acquiring high through-plane resolution volumetric MSOT is time-consuming. Here, we propose a deep learning model based on hybrid recurrent and convolutional neural networks to generate sequential cross-sectional images for an MSOT system. This system provides three modalities (MSOT, ultrasound, and optoacoustic imaging of a specific exogenous contrast agent) in a single scan. This study used ICG-conjugated nanoworms particles (NWs-ICG) as the contrast agent. Instead of acquiring seven images with a step size of 0.1 mm, we can receive two images with a step size of 0.6 mm as input for the proposed deep learning model. The deep learning model can generate five other images with a step size of 0.1 mm between these two input images meaning we can reduce acquisition time by approximately 71%.

Cholesterol crystals induce mechanical trauma, inflammation, and neo-vascularization in solid cancers as in atherosclerosis.

Background and aims: Cancer and atherosclerosis share common risk factors and inflammatory pathways that promote their proliferation via vascular endothelial growth factor (VEGF). Because CCs cause mechanical injury and inflammation in atherosclerosis, we investigated their presence in solid cancers and their activation of IL-1ß, VEGF, CD44, and Ubiquityl-Histone H2B (Ub-H2B), that promote cancer growth. Methods: Tumor specimens from eleven different types of human cancers and atherosclerotic plaques were assessed for CCs, free cholesterol content and IL1-ß by microscopy, immunohistochemistry, and biochemical analysis. Breast and colon cancer cell lines were cultured with and without CCs to select for expression of VEGF, CD44, and Ub-H2B. Western blot and immunofluorescence were performed on cells to assess the effect of CCs on signaling pathways. Results: Cancers displayed higher CC content (+2.29 ± 0.74 vs +1.46 ± 0.84, p < 0.0001), distribution (5.06 ± 3.13 vs 2.86 ± 2.18, p < 0.001) and free cholesterol (3.63 ± 4.02 vs 1.52 ± 0.56 µg/mg, p < 0.01) than cancer free marginal tissues and similarly for atherosclerotic plaques and margins (+2.31 ± 0.51 vs +1.44 ± 0.79, p < 0.02; 14.0 ± 5.74 vs 8.14 ± 5.52, p < 0.03; 0.19 ± 0.14 vs 0.09 ± 0.04 µg/mg, p < 0.02) respectively. Cancers displayed significantly increased expression of IL1-ß compared to marginal tissues. CCs treated cancer cells had increased expression of VEGF, CD44, and Ub-H2B compared to control. By microscopy, CCs were found perforating cancer tumors similar to plaque rupture. Conclusions: These findings suggest that CCs can induce trauma and activate cytokines that enhance cancer growth as in atherosclerosis.

21-Gene recurrence scores: racial differences in testing, scores, treatment, and outcome.

BACKGROUND: African American (AA) women experience higher breast cancer mortality than white (W) women. These differences persist even among estrogen receptor (ER)-positive breast cancers. The 21-gene recurrence score (RS) predicts recurrence in patients with ER-positive/lymph node-negative breast cancer according to RS score-low risk (RS, 0-18), intermediate risk (RS, 19-31), and high risk (RS, >31). The high-risk group is most likely to benefit from chemotherapy, to achieve minimal benefit from hormonal therapy, and to exhibit lower ER levels (intrinsically luminal B cancers). In the current study, the authors investigated racial differences in RS testing, scores, treatment, and outcome. METHODS: Tumor registry data from 3 Atlanta hospitals identified women who were diagnosed with breast cancers during 2005 through 2009. Medical record abstraction provided information on RS and other tumor/treatment factors. Statistical analyses used chi-square/exact tests and logistic regression. RESULTS: Of 2186 patients, including 1192 AA women and 992 W women, 853 women had stage I or II, ER-positive/lymph node-negative disease and, thus, were eligible for RS testing (AA = 372 [31.2%]; W = 481 [48.5%]; P < .0001); and 272 women (31.8%) received testing (AA = 76 [20.4%]; W = 196 [40.7%]; P < .0001). Tumors were distributed into the following groups according to risk: low risk (n = 133), medium risk (n = 113), and high risk (n = 26). The mean RS did not differ by race, but risk groups did (low-risk group: 46.1% vs 50% for AA women and W women, respectively; high-risk group: 15.8% vs 7.1%, respectively; P = .043). In multivariate analyses, AA race (odds ratio, 3.6) was associated independently with high risk scores. CONCLUSIONS: AA women were half as likely as W women to receive 21-gene RS testing but were 2-fold more likely to be categorized as high risk. The current data suggested that testing guidelines are not applied equivalently, testing bias may attenuate racial differences in RS, and disparate outcomes may be explained in part by differences in RS, although compliance and pharmacogenomics also may play a role.

Feasibility of accelerated partial breast irradiation in a large inner-city public hospital.

BACKGROUND: Breast conserving therapy (BCT) that include breast conserving surgery followed by adjuvant radiation therapy has revolutioned medicine by allowing women to avoid mastectomy. Accelerated partial breast irradiation (APBI) has emerged as a valid alternative to whole-breast irradiation that requires a shorter time commitment. We report our novel experience with APBI at a large public hospital that serves low-income and potentially noncompliant patients. METHODS: A retrospective chart review was conducted of women who underwent BCT for stage 0-IIA breast cancer from August 2007 to August 2010 treated with APBI with a brachytherapy catheter. RESULTS: Twenty-four patients (20 African American) were considered for APBI. Average age was 61 years. Four patients could not undergo APBI for technical reasons and completed whole-breast irradiation over a 5 week period. Median follow-up was 19 months. Nine patients (37.5 %) had ductal carcinoma-in-situ, and 15 patients (62.5 %) had invasive ductal carcinoma with an average tumor size of 1.1 cm. All patients had negative margins of >2 mm. Two patients (8 %) treated with the brachytherapy catheter had in-breast tumor recurrence. Thus, all 24 patients initially identified for APBI successfully completed adjuvant radiotherapy. CONCLUSIONS: Patient compliance with postoperative irradiation is key to minimize local recurrence after BCT for breast cancer. This success with a brachytherapy catheter in underserved women in a U.S. public hospital setting indicates that outcomes of compliance and complications are comparable to nationally published results.

Pseudoangiomatous stromal hyperplasia (PASH) of the breast: a series of 24 patients.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign mesenchymal proliferative lesion of the breast. In 2005, only 109 cases had been reported since its initial description in 1986 by Vuitch et al. Our 24 cases represent one of the largest series to be reported from a single institution. We retrospectively reviewed data from 2004 to 2010 of patients diagnosed with PASH by surgical excision or image-guided biopsy. All pathological specimens were reviewed by a single pathologist. The samples were stained for estrogen and progesterone receptors (ER and PR), CD34, and the lymphatic marker D2-40. All but one of 24 (96%) patients presented with breast masses either on imaging or clinically. Fourteen of the 24 patients (58%) were diagnosed on surgical excision, 10 (42%) diagnosed with core needle biopsy, and five (20%) were diagnosed using both techniques. The tumors ranged in size from 0.3 cm to 7.0 cm. All women except two were premenopausal or perimenopausal at diagnosis. Nineteen samples were available for hormonal receptor staining and of these 18 of 19 (95%) were ER or PR positive. PASH was diagnosed in two men, a transgender male on hormones and the other with gynecomastia. The patients' ages ranged from 18 to 86 years old. In addition to PASH other benign histopathological findings include stromal fibrosis and atypical ductal or lobular hyperplasia. Imaging revealed no distinguishing feature for PASH with benign histology. One patient had synchronous ductal carcinoma in-situ (DCIS). Patients were treated with local excision or observation. This study suggests that PASH is primarily a diagnosis of premenopausal and perimenopausal women. Our series supports a hormonal basis for its development due to the positive staining for hormonal receptors. Management is conservative surgery for larger masses with careful observation being an option in patients not at high risk for breast cancer.

Improving on national quality indicators of breast cancer care in a large public hospital as a means to decrease disparities for African American women.

BACKGROUND: In April 2007, the National Quality Forum (NQF) endorsed the first nationally recognized hospital-based performance measures for stage I, II, and III breast cancer. The purpose of this study was to document compliance with the 3 NQF breast quality indicators during 2 time intervals in a metropolitan public hospital. MATERIALS AND METHODS: Tumor registry and medical records were used to identify patient demographics and treatments before (2005-2006) and after (2008) implementations in 2007 as a result of the NQF audit. Program changes included: hiring a dedicated medical oncology nurse practitioner, requiring the radiation oncology case manager to attend weekly multidisciplinary conferences, educating Patient Navigators of the importance of multimodal care, and providing support groups for patients addressing importance of completion of all treatment options. RESULTS: A total of 213 female patients were diagnosed with and treated for stage I, II, or III breast cancer in 2005-2006 and 2008. Of these, 189 (89%) were African American (AA) women. Also, 70 patients of 86 (81.3%) received radiation therapy, 60 of 77 (77.9%) received or were considered for adjuvant chemotherapy, and 124 of 144 (86.1%) for hormonal therapy according to NQF indicators. After 2007, patients receiving radiation therapy increased from 75.8 to 95.8%. Patients receiving or considered for adjuvant chemotherapy or hormonal therapy increased from 73.7 to 93.7% and from 84.1 to 90.0%, respectively. CONCLUSIONS: NQF breast cancer indicators provided a mechanism to improve compliance of multimodal treatment in our center. Raising awareness of these indicators in the multidisciplinary conference, hiring dedicated personnel, and educating patients has led to major improvements in breast cancer care.

Prognostic significance of p53 codon 72 polymorphism differs with race in colorectal adenocarcinoma.

PURPOSE: Several studies have examined the prognostic value of the codon 72 polymorphism of the p53 gene in colorectal adenocarcinoma, but none have addressed patient race/ethnicity. Therefore, this study assessed the prognostic value of this polymorphism in African American and Caucasian colorectal adenocarcinoma patients separately. EXPERIMENTAL DESIGN: Colorectal adenocarcinomas from 137 African Americans and 236 non-Hispanic Caucasians were assessed for p53 mutations and genotyped for the codon 72 polymorphism. The phenotypes were correlated with p53 mutational status, clinicopathologic features, and patient survival using the chi(2) test and Kaplan-Meier and Cox regression models. RESULTS: The incidence of p53 mutations was similar in African American and Caucasian patients (50% versus 54%, respectively); however, the homozygous Pro72 allele frequency was higher in African Americans (17%) as compared with Caucasians (7%). In contrast, the homozygous Arg72 allele frequency was higher in Caucasians (36%) than in African Americans (19%). In African Americans but not Caucasians, the Pro/Pro phenotype significantly correlated with a higher incidence of missense p53 mutations and with nodal metastasis. African Americans, but not Caucasians, with the Pro/Pro phenotype had significantly higher mortality (log-rank P = 0.005 versus. P = 0.886) and risk of death due to colorectal adenocarcinoma (hazard ratio, 2.15; 95% confidence interval, 1.02-4.53 versus hazard ratio, 1.60; 95% confidence interval, 0.69-3.18) than those with the phenotype Arg/Arg or Arg/Pro. CONCLUSIONS: The higher frequency of the Pro/Pro phenotype of p53 in African American patients with colorectal adenocarcinoma is associated with an increased incidence of p53 mutations, with advanced tumor stage, and with short survival.

Using National Quality Forum breast cancer indicators to measure quality of care for patients in an AVON comprehensive breast center.

In April 2007, the National Quality Forum (NQF) endorsed the first nationally recognized hospital-based performance measures for quality of care for breast cancer. The aim of this study was to measure quality of care at our AVON Center for Breast Care (AVONCBC) using these indicators. We retrospectively reviewed tumor registry and medical records of females under age 70 diagnosed with breast cancer in years 2005-2006. For patients diagnosed with hormone receptor negative breast cancer, 22 of 29 (75.9%) and 28 of 32 (87.5%) were considered for or received chemotherapy in 2005 and 2006, respectively. Of those patients, 21 of 29 (72.4%) and 24 of 32 (75.0%) were considered for or received chemotherapy within the NQF 4-month period. For patients undergoing breast conserving surgery (BCS), 20 of 23 (86.9%) in 2005 and 37 of 39 (94.9%) in 2006 were referred for adjuvant radiation therapy. The proportion of patients who received radiation therapy within 1 year of diagnosis was 18 of 23 (78.2%) and 29 of 39 (74.4%) for diagnosis years 2005 and 2006, respectively. The vast majority of patients in our AVONCBC are referred to medical and/or radiation oncology for adjunctive therapy and about three-fourths receive treatment compliant with the NQF QI. To increase our compliance rate, we are developing methods to improve access to the multiple disciplines in our AVONCBC. Using the NQF indicators serves to assess hospital performance at a systems-level and as a useful method for tracking cancer quality of care.

CXCR4-gp120-IIIB interactions induce caspase-mediated apoptosis of prostate cancer cells and inhibit tumor growth.

CXC chemokine receptor 4 (CXCR4) has been implicated in prostate cancer metastasis and this receptor also acts as a coreceptor for HIV-1 120-kDa glycoprotein variant IIIB (gp120-IIIB). The interaction between CXCR4 and gp120-IIIB has been shown to mediate apoptosis of both immune and endothelial cells. In this study, we have examined the effects of gp120-IIIB on hormone-refractory prostate cancer cells (PC3 and DU145) in vitro and tumor growth in vivo. Normal prostatic epithelial (PrEC) and prostate cancer cell lines were treated with gp120-IIIB with or without anti-CXCR4 antibody. Caspase expression was evaluated by real-time PCR and active caspase assays. Apoptosis was determined by flow cytometry. gp120-IIIB treatment correlated with active caspase-3 and -9 expression and apoptosis of prostate cancer cells but not PrEC cells. This effect was significantly inhibited after CXCR4 blockade. PC3 and DU145 tumor-bearing mice received intraperitoneal injections of gp120-IIIB and controls received bovine serum albumin in PBS. PC3 and DU145 tumor sizes were measured over time and excised tumors were evaluated for CD44, CD34, lymphatic endothelial cell marker LYVE-1, active caspase-3, and active caspase-9 expression by immunohistochemistry. The tumor size in mice receiving gp120-IIIB was significantly smaller than compared with tumors in control mice. This regression was associated with significant decreases in CD44, CD34, and LYVE-1 and increases in active caspase-3 and -9 expression. These results suggest that gp120-IIIB induced apoptosis in prostate cancer cells and reduced tumor-associated lymphoendothelial cells.

Functional consequence of the p53 codon 72 polymorphism in colorectal cancer.

BACKGROUND: The codon 72 polymorphism in p53 has been implicated in colorectal cancer (CRC) risk, prognosis and CRC health disparities. We examined the functional consequence of this polymorphism in CRC. EXPERIMENTAL DESIGN: Plasmids (pCMV6) that express different phenotypes of p53 [p53 wild type (wt) at codon 72 (R72wt), R72wt with mutation at codon 273 cysteine (R72273Cys), p53 mutation at codon 72 (P72wt) and P72wt with mutation at codon 273 (P72273Cys)] were constructed. The CRC cell line Caco2, which does not express p53 for in vitro studies, was used as host. CRC xenografts were established in severe combined immunodeficient (SCID) mice using established cell lines. CRC surgical specimens, corresponding normal colon, and tumor xenografts were sequenced for codon 72 polymorphism of p53. Proteins signaling mechanisms were evaluated to assess the functional consequence of P72 phenotype of p53. RESULTS: This study demonstrated a significantly increased survival of cells expressing P72wt, mutant phenotype, versus R72wt phenotype. WB analyses revealed that P72wt induced activation of p38 and RAF/MEK/ extracellular signal-regulated kinase (ERK) MAP kinases. Activation of CREB was found to be higher in tumors that exhibit P72 phenotype. Metastatic lesions of CRC expressed more phospho-CREB than non-metastatic lesions. The expression of P72wt promoted CRC metastasis. CONCLUSIONS: P72 contributes to the aggressiveness of CRC. Because P72 is over-expressed in CRC, specifically in African-American patients, this suggests a role for P72 in cancer health disparities. This work was supported by NIH/NCI Workforce Diversity Grant R21-CA171251 & U54CA118948.

Effects of HIV-1 Nef, a cytotoxic viral protein, on the growth of primary colorectal cancer.

Colorectal cancer is the third leading cause of cancer deaths in American men and women. We describe the cytotoxic use of HIV-1 Nef protein and a cytotoxic peptide identified within the HIV-1 Nef structure in targeting human cancer cells in vitro and in vivo in a human xenograft model. A human colorectal tumor was implanted and propagated in the subcutaneous tissue of SCID mice. The mice were injected biweekly with the Nef apoptotic peptide. The tumor treated with Nef peptide underwent significant growth inhibition by as much as 300 percent when compared to the control (untreated) tumors. The Nef peptides were found to have an apoptotic effect on the human colon tumor similar to the effect seen on CD4 cells when the viral protein is secreted by the HIV-1 virus infected cells. The evidence from the xenograft mouse model suggests that the Nef peptides can be used to inhibit human colorectal cancer growth.

Nef-M1, a peptide antagonist of CXCR4, inhibits tumor angiogenesis and epithelial­to­mesenchymal transition in colon and breast cancers.

The Nef-M1 peptide competes effectively with the natural ligand of CXC chemokine receptor 4 (CXCR4), stromal cell-derived factor 1-alpha, to induce apoptosis and inhibit growth in colon cancer (CRC) and breast cancer (BC). Its role in tumor angiogenesis, and epithelial-to-mesenchymal transition (EMT) regulation, key steps involved in tumor growth and metastasis, are unknown. We evaluated the angioinhibitory effect of Nef-M1 peptide and examined its role in the inhibition of EMT in these cancers. Colon (HT29) and breast (MDA-MB231) cancer cells expressing CXCR4 were studied in vitro and in xenograft tumors propagated in severe combined immunodeficient mice. The mice were treated intraperitoneally with Nef-M1 or scrambled amino acid sequence of Nef-M1 (sNef-M1) peptide, a negative control, starting at the time of tumor implantation. Sections from tumors were evaluated for tumor angiogenesis, as measured by microvessel density (MVD) based on immunostaining of endothelial markers. In vitro tumor angiogenesis was assessed by treating human umbilical vein endothelial cells with conditioned media from the tumor cell lines. A BC cell line (MDA-MB 468) which does not express CXCR4 was used to study the actions of Nef-M1 peptide. Western blot and immunofluorescence analyses assessed the effect of Nef-M1 on tumor angiogenesis and EMT in both tumors and cancer cells. Metastatic lesions of CRC and BC expressed more CXCR4 than primary lesions. It was also found that tumors from mice treated with sNef-M1 had well established vascularity, while Nef-M1 treated tumors had very poor vascularization. Indeed, the mean MVD was lower in tumors from Nef-M1 treated mice than in sNef-M1 treated tumors. Nef-M1 treated tumor has poor morphology and loss of endothelial integrity. Although conditioned medium from CRC or BC cells supported HUVEC tube formation, the conditioned medium from Nef-M1 treated CRC or BC cells did not support tube formation. Western blot analyses revealed that Nef-M1 effectively suppressed the expression of VEGF-A in CRC and BC cells and tumors. This suggests that Nef-M1 treated CRC and BC cells are more consistent with E-cadherin signature, and thus appears more epithelial in nature. Our data indicate that Nef-M1 peptide inhibits tumor angiogenesis and the oncogenic EMT process. Targeting the chemokine receptor, CXCR4, mediated pathways using Nef-M1 may prove to be a novel therapeutic approach for CRC and BC.

Phyllodes tumors in African American women.

BACKGROUND: Phyllodes is a rare tumor accounting for less than 1% of all breast neoplasms. Studies defining clinical predictors of malignant phyllodes (MP) are rare and inconsistent. Furthermore, MP occurrence in African American (AA) women has never been analyzed. This study will delineate clinical and pathologic features in AA patients that may reasonably predict the probability of malignancy. METHODS: A retrospective study of clinical records was carried out for 50 AA patients diagnosed with phyllodes tumors (PT) and treated between 1982 and 2012. Patients' charts were analyzed regarding demographics, pathology findings, and treatment. RESULTS: The diagnosis of benign disease was made in 40 (78%), borderline in 3 (6%), and malignancy in 7 (14%) patients; however, 1 patient (2%) had mixed phyllodes with ductal carcinoma in situ. The mean age was significantly different for patients with benign disease (33 years) compared with those with malignancy (54 years; P < .001). The average tumor size was twice as large (11.8 vs 4.1 cm; P = .029) and mitoses were higher with 50% of MPs having greater than 5 per 10 high power fields. Although rare, nodal metastasis, ulceration, and multicentric disease occurred only in MP. CONCLUSIONS: Among AA patients with phyllodes tumors, those with malignant tumors were older and had larger tumors and higher mitotic indices than those with benign disease. AA patients also displayed some of the more rare features of advanced disease and presented with malignancy near the highest reported frequency.

Unusual complications of long-term percutaneous gastrostomy tubes.

Percutaneous endoscopic gastrostomy (PEG) has been popular since it was introduced in 1980. Gastrostomy tubes left in place for long periods often result in unusual complications. Complications may also result from simply replacing a long-term indwelling tube. Five patients who had gastrostomy tubes in place for as long as 4 years are presented and their complications reviewed. Various methods used in treating these complications are discussed, and suggestions for their prevention are given. Gastrointestinal erosion and jejunal perforation following migration of the gastrostomy tube, persistent abdominal wall sinus tracts, and separation of the flange head with small bowel obstruction were encountered. Reinsertion of a gastrostomy tube through a tract prior to adequate maturation was also noted to lead to complications. Complications may result from gastrostomy tubes left in place for extended periods of time and during replacement procedures. Awareness of such complications along with education of caregivers and timely intervention by the endoscopist may prevent such occurrences. In some cases one can only hope to minimize morbidity.