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A Pilot Study Of Circulating Tumor Cells In Stage Iv Non-Small Cell Lung Carcinoma, Max Haid, Edward Chesna, Mary Theodoroff, Debra K. Spaeth, Cheruppolil R. Santhosh-Kumar, Zahid N. Dar 2016 Sheboygan Acupuncture

A Pilot Study Of Circulating Tumor Cells In Stage Iv Non-Small Cell Lung Carcinoma, Max Haid, Edward Chesna, Mary Theodoroff, Debra K. Spaeth, Cheruppolil R. Santhosh-Kumar, Zahid N. Dar

Journal of Patient-Centered Research and Reviews

Purpose

Measurement of the number of circulating tumor cells (CTCs) in the bloodstream has been shown to have prognostic significance in treating breast carcinoma. This pilot study was formulated to determine if stage IV non-small cell lung carcinomas similarly shed malignant cells into the circulation and if their presence has prognostic significance.

Methods

Patients with stage IV non-small cell lung carcinomas were tested once for CTCs in 7.5 ml of their blood prior to receiving any treatments. A proprietary blood collection kit produced by Veridex LLC (Raritan, NJ), which manufactures the instrument that performs the immunomagnetic CELLSEARCH® CTC assay ...


Hospice And Pain Management In Nursing Home Residents With Cancer, Jacob N. Hunnicutt, Jennifer Tjia, Kate L. Lapane 2016 University of Massachusetts Medical School

Hospice And Pain Management In Nursing Home Residents With Cancer, Jacob N. Hunnicutt, Jennifer Tjia, Kate L. Lapane

Jennifer Tjia

Background: The prevalence of untreated pain in nursing home residents with cancer is unacceptably high. Hospice may increase the likelihood of receiving pain management at the end of life.

Objectives: To estimate whether receipt of hospice in nursing homes increases the receipt of pain management for nursing home residents with cancer at the end of life.

Methods: We conducted a cross-sectional study on a national sample of Medicare decedents who had cancer and were nursing home residents during the last 90 days of life in 2011–2012. We used the last Minimum Data Set (MDS) 3.0 assessment before death ...


Alcoholic Hepatitis Accelerates Early Hepatobiliary Cancer By Increasing Stemness And Mir-122-Mediated Hif-1alpha Activation, Aditya Ambade, Abhishek Satishchandran, Gyongyi Szabo 2016 University of Massachusetts Medical School

Alcoholic Hepatitis Accelerates Early Hepatobiliary Cancer By Increasing Stemness And Mir-122-Mediated Hif-1alpha Activation, Aditya Ambade, Abhishek Satishchandran, Gyongyi Szabo

Gyongyi Szabo

Alcohol-related hepatocellular carcinoma (HCC) develops with advanced alcoholic liver disease and liver fibrosis. Using adult mice, we evaluate the effect of alcoholic steatohepatitis on early hepatobiliary carcinoma after initiation by diethyl-nitrosamine (DEN). Here we show that alcohol-fed DEN-injected mice have higher ALT and liver-to-body weight ratio compared to pair-fed DEN-injected mice. Alcohol feeding results in steatohepatitis indicated by increased pro-inflammatory cytokines and fibrotic genes. MRI and liver histology of alcohol+DEN mice shows hepatobiliary cysts, early hepatic neoplasia and increase in serum alpha-fetoprotein. Proliferation makers (BrdU, cyclin D1, p53) and cancer stem cell markers (CD133 and nanog) are significantly up-regulated ...


Beta1 Integrin- And Jnk-Dependent Tumor Growth Upon Hypofractionated Radiation, Aejaz Sayeed, Huimin Lu, Qin Liu, David Deming Ii, Alexander Duffy, Peter McCue, Adam P. Dicker, Roger J. Davis, Dmitry Gabrilovich, Ulrich Rodeck, Dario C. Altieri, Lucia R. Languino 2016 Thomas Jefferson University

Beta1 Integrin- And Jnk-Dependent Tumor Growth Upon Hypofractionated Radiation, Aejaz Sayeed, Huimin Lu, Qin Liu, David Deming Ii, Alexander Duffy, Peter Mccue, Adam P. Dicker, Roger J. Davis, Dmitry Gabrilovich, Ulrich Rodeck, Dario C. Altieri, Lucia R. Languino

Open Access Articles

Radiation therapy is an effective cancer treatment modality although tumors invariably become resistant. Using the transgenic adenocarcinoma of mouse prostate (TRAMP) model system, we report that a hypofractionated radiation schedule (10 Gy/day for 5 consecutive days) effectively blocks prostate tumor growth in wild type (beta1wt /TRAMP) mice as well as in mice carrying a conditional ablation of beta1 integrins in the prostatic epithelium (beta1pc-/- /TRAMP). Since JNK is known to be suppressed by beta1 integrins and mediates radiation-induced apoptosis, we tested the effect of SP600125, an inhibitor of c-Jun amino-terminal kinase (JNK) in the TRAMP model system. Our results ...


Ultrasound-Guided Intralesional Bleomycin Injection (Ibi) For Treatment Of Cutaneous Hemangiomas And Vascular Malformations, Yousuf Memon, Nuzhat I. Malik, Naveed Anjum, S. Kamran Ahmed, Sadaf Saeed 2016 The Indus Hospital

Ultrasound-Guided Intralesional Bleomycin Injection (Ibi) For Treatment Of Cutaneous Hemangiomas And Vascular Malformations, Yousuf Memon, Nuzhat I. Malik, Naveed Anjum, S. Kamran Ahmed, Sadaf Saeed

The Journal of Global Radiology

Purpose: To report the therapeutic outcome of ultrasound-guided intralesional injection of bleomycin in the treatment of cutaneous hemangiomas and vascular malformations.

Material & Methods: The medical records of patients with cutaneous hemangiomas and vascular malformations treated with the intralesional injection of bleomycin under ultrasound guidance between August 2009 and June 2013 at the Indus Hospital, Karachi were reviewed retrospectively using a computerized medical record information management system. Data were extracted using a pre-coded performa that included patient demographics, type and location of lesion, number of treatments, presenting/pre- and post-treatment clinical symptoms (pain, swelling, heaviness, size, discoloration), ultrasound appearance and vascularity, and post-treatment side effects. The dose range of bleomycin was 0.5-1.0 mg/kg, but not exceeding 15 mg in a single session. A maximum of four treatments were given in any given patient except for one, who presented with recurrence after a year of complete resolution. Therapeutic outcome was determined using review of ultrasound images and recorded clinical assessment. Treatment response was categorized as: (i) complete resolution [more than 90% reduction]; (ii) substantial reduction [more than 50% reduction]; (iii) mild reduction [25% reduction]; or, (iv) no improvement [ < 10% reduction].

Results: A total of 30 patients (16 female, 14 male), ranging in age from 8 months to 48 years (mean age 10.2 years), were treated from 2009 to 2013. There were 23 hemangiomas. Seven were vascular malformations, of which five were lymphatic malformations and two were venous malformations. Twenty-eight lesions were located in the head and neck region, and two were ...


The Impact Of Changing Guidelines On Prostate Cancer Screening In A Population-Based Setting, 2000-2014, Daniel M. Frendl, Mara M. Epstein, Hassan Fouayzi, Richard Krajenta, Benjamin A. Rybicki, Mitchell H. Sokoloff 2016 University of Massachusetts Medical School

The Impact Of Changing Guidelines On Prostate Cancer Screening In A Population-Based Setting, 2000-2014, Daniel M. Frendl, Mara M. Epstein, Hassan Fouayzi, Richard Krajenta, Benjamin A. Rybicki, Mitchell H. Sokoloff

UMass Center for Clinical and Translational Science Research Retreat

Introduction: This study evaluates the potential impact of the publication of conflicting prostate cancer (PCa) screening trial results in 2009 and changes to the US Preventive Services Task Force (USPSTF) guidelines to recommend against screening in 2012 on temporal trends in PSA testing at two participating sites in the NCI-funded Cancer Research Network.

Methods: Study participants were men aged 40-80 without a history of PCa who sought care at Fallon Health (Worcester, MA) or Henry Ford Health System (Detroit, MI) between 2000-2014. We used health claims and electronic health record data to identify men who underwent PSA testing per calendar ...


Analysis Of A Novel Nonsense Mutation Of Androgen Receptor Gene In Castration-Resistant Prostate Cancer, Dong Han, Kevin Valencia, Shuai Gao, Changmeng Cai 2016 University of Massachusetts Boston

Analysis Of A Novel Nonsense Mutation Of Androgen Receptor Gene In Castration-Resistant Prostate Cancer, Dong Han, Kevin Valencia, Shuai Gao, Changmeng Cai

UMass Center for Clinical and Translational Science Research Retreat

BACKGROUND: Prostate cancer (PCa) is the second leading cause of cancer mortality in American men. The standard treatment for PCa is androgen deprivation therapy (ADT) that blocks transcriptional activity of androgen receptor, but ADT invariably leads to the development of castration-resistant form of PCa (CRPC) with restored activity of AR. CRPC can be further treated with more intensive ADTs, including CYP17-inhibitors to block intratumoral androgen synthesis and more potent AR antagonist (enzalutamide). Most CRPC patients still relapse after a year of treatment and AR activity appears to be restored again. By analyzing the tumor mRNA from a CRPC patient biopsy ...


Hospice And Pain Management In Nursing Home Residents With Cancer, Jacob N. Hunnicutt, Jennifer Tjia, Kate L. Lapane 2016 University of Massachusetts Medical School

Hospice And Pain Management In Nursing Home Residents With Cancer, Jacob N. Hunnicutt, Jennifer Tjia, Kate L. Lapane

UMass Center for Clinical and Translational Science Research Retreat

Background: The prevalence of untreated pain in nursing home residents with cancer is unacceptably high. Hospice may increase the likelihood of receiving pain management at the end of life.

Objectives: To estimate whether receipt of hospice in nursing homes increases the receipt of pain management for nursing home residents with cancer at the end of life.

Methods: We conducted a cross-sectional study on a national sample of Medicare decedents who had cancer and were nursing home residents during the last 90 days of life in 2011–2012. We used the last Minimum Data Set (MDS) 3.0 assessment before death ...


Targeted Combination Treatment For Glioblastoma Multiforme (Gbm) Using Polymeric Nanoparticle, Praveena Velpurisiva, Michael Tilton, Brandon Piel, Prakash Rai 2016 University of Massachusetts Lowell

Targeted Combination Treatment For Glioblastoma Multiforme (Gbm) Using Polymeric Nanoparticle, Praveena Velpurisiva, Michael Tilton, Brandon Piel, Prakash Rai

UMass Center for Clinical and Translational Science Research Retreat

Glioblastoma Multiforme (GBM) is an aggressive cancer that originates from astrocytes and spreads to spinal cord and other parts of the brain. Increase in replication of glial cells leads to advantageous mutations in the tumor. In 2015 about 15,320 deaths were reported due to GBM. Five-year survival is less than 5% making GBM a dreadful cancer. Current treatment involves complex invasive surgery, followed by chemotherapy and radiation. There is a desperate unmet need for a targeted treatment of GBM with minimum damage to the surrounding normal tissue. Combination treatments are increasingly being used to target multiple hallmarks of cancer ...


Implantable Microenvironments To Capture Stable-To- Aggressive Tumor Transition, Ryan Carpenter, Jungwoo Lee 2016 University of Massachusetts Amherst

Implantable Microenvironments To Capture Stable-To- Aggressive Tumor Transition, Ryan Carpenter, Jungwoo Lee

UMass Center for Clinical and Translational Science Research Retreat

Clinical stability occurs when cancers reach a state where the disease neither advances nor regresses. Tumors can remain in this state for multiple years before progressing to more aggressive phenotypes. The mechanisms for maintaining a stable state and the factors that contribute to tumor activation are poorly understood. We hypothesized that an implantable biomaterial scaffold would be able to isolate a population of stable tumor cells that could then be used to study the transition to an aggressive phenotype. In this work we developed a tunable and highly controlled, porous acrylamide scaffold and subcutaneously implanted them in immunodeficient (NSG) mice ...


Transferrin Conjugated Polymeric Nanomedicine For Targeting Pancreatic Cancer Using Paclitaxel And Gemcitabine, Aniket Gad, Michael Tilton, Brandon Piel, Prakash Rai 2016 University of Massachusetts Lowell

Transferrin Conjugated Polymeric Nanomedicine For Targeting Pancreatic Cancer Using Paclitaxel And Gemcitabine, Aniket Gad, Michael Tilton, Brandon Piel, Prakash Rai

UMass Center for Clinical and Translational Science Research Retreat

Pancreatic cancer (PanCa) has a dismal prognosis with five-year survival rates under 5%. PanCa is usally diagnosed at very late stages and even if diagnosed early, surgery is rarely an option. These factors contribute towards the bleak statistics for PanCa Chemo and radiation treatments having deleterious side-effects. There is therefore a clinical, unmet need for novel, targeted treatments with low morbidity in PanCa. Gemzar® (gemcitabine-HCl) is an FDA (Food and Drug Administration) approved chemotherapeutic drug that has been used to treat PanCa. However, intrinsic and acquired chemoresistance to gemcitabine contribute to the poor prognosis of PanCa. A combination of Abraxane ...


Identification Of Gdf-6 Blocking Antibodies As Anti-Melanoma Therapeutics, Ejemel Monir, Danielle Wisheart, Alec Gramann, Arvind Venkatesan, Mark S. Klempner, Craig J. Ceol, Yang Wang 2016 University of Massachusetts Medical School

Identification Of Gdf-6 Blocking Antibodies As Anti-Melanoma Therapeutics, Ejemel Monir, Danielle Wisheart, Alec Gramann, Arvind Venkatesan, Mark S. Klempner, Craig J. Ceol, Yang Wang

UMass Center for Clinical and Translational Science Research Retreat

Through comparative oncogenomic studies and functional analyses, we have identified the bone morphogenetic protein (BMP) factor GDF6 as a new melanoma oncogene. The secreted, carboxy-terminal portion of GDF6 is the active form that binds to cell-surface receptors to initiate BMP signaling. Targeted antibodies directed against secreted proteins are a proven therapeutic modality in several diseases.

To develop therapeutic antibodies against the active form of GDF6, we generated a panel of monoclonal antibodies. Due to the high similarity of human and mouse GDF6 proteins, the C-terminal GDF6 protein was expressed as bacterial recombinant protein with fusion tags to enhance immunogenicity. The ...


Developing Anti-Gdf6 Therapeutics For Treatment Of Advanced Melanoma, Alec Gramann, Arvind Venkatesan, Ejemel Monir, Danielle Wisheart, Yan Wang, Craig J. Ceol 2016 University of Massachusetts Medical School

Developing Anti-Gdf6 Therapeutics For Treatment Of Advanced Melanoma, Alec Gramann, Arvind Venkatesan, Ejemel Monir, Danielle Wisheart, Yan Wang, Craig J. Ceol

UMass Center for Clinical and Translational Science Research Retreat

Melanoma, the leading cause of skin cancer death in the U.S., is increasing in incidence. Targeted therapies have been approved for treatment of advanced melanoma, but few patients experience extended survival benefit. In order to combat poor outcomes, new therapeutic targets are needed. Using cross-species oncogenomic analyses, our lab has identified a novel melanoma driver, Growth differentiation factor 6 (GDF6), a secreted bone morphogenetic protein (BMP) ligand that is amplified and overexpressed in human melanomas. Functional analyses show GDF6 acts via the BMP-SMAD1 pathway as a pro-survival factor in melanomas. Inhibiting GDF6 or the BMP pathway using shRNAs or ...


Remotely Triggered Polymeric Nanoparticles For The Treatment Of Triple Negative Breast Cancer, Rahul Jadia, Brandon Piel, Michael Tilton, Prakash Rai 2016 University of Massachusetts Lowell

Remotely Triggered Polymeric Nanoparticles For The Treatment Of Triple Negative Breast Cancer, Rahul Jadia, Brandon Piel, Michael Tilton, Prakash Rai

UMass Center for Clinical and Translational Science Research Retreat

Triple Negative Breast Cancer (TNBC) has the worst prognosis among all the sub-types of breast cancer. Currently no targeted treatment has been approved for TNBC management. While TNBC does not overexpress hormone receptors, it has been found to over express certain receptors like transferrin (TfR) or folate receptors. The aim of this research is to synthesize targeted polymeric nanoparticles for TNBC. MDA-MB-231 cells are used as a representative TNBC cell line in this study. Active targeting of TNBC is achieved by conjugating the nanoparticles to a peptide (Tr) that binds to the TfR. Photodynamic Therapy (PDT) using polymeric nanoparticles was ...


5-Hyroxymethylcytosine Immunohistochemical Staining Correlates With Overall Survival In Patients With Chronic Myelomonocytic Leukemia, William Selove, Karen A. Dresser, Benjamin Chen 2016 University of Massachusetts Medical School

5-Hyroxymethylcytosine Immunohistochemical Staining Correlates With Overall Survival In Patients With Chronic Myelomonocytic Leukemia, William Selove, Karen A. Dresser, Benjamin Chen

UMass Center for Clinical and Translational Science Research Retreat

Introduction Chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative neoplasm that has been associated with a number of genetic mutations, most commonly TET2 mutations in up to 50-60% of cases. Mutations in epigenetic genes such as TET2 are known to disrupt the conversion of 5-methycytosine to 5-hydroxymethylcytosine (5hmC), contributing to oncogenesis. We hypothesized that CMML cases would exhibit decreased 5hmC expression, reflecting the propensity for TET2 mutations in CMML. We also sought to determine whether 5hmC IHC status reflected disease severity in terms of progression to AML and overall patient survival.

Methods Thirty-five cases of CMML from between 1/2006 ...


Contemporary Analysis Of Malignancies In Women Of Child-Bearing Age: An Nsqip Analysis, Eva Rouanet, Ann-Kristin U. Friedrich, Kate Dinh, Kevin P. Baratta, Giles F. Whalen, Heena Santry, Jennifer LaFemina 2016 University of Massachusetts Medical School

Contemporary Analysis Of Malignancies In Women Of Child-Bearing Age: An Nsqip Analysis, Eva Rouanet, Ann-Kristin U. Friedrich, Kate Dinh, Kevin P. Baratta, Giles F. Whalen, Heena Santry, Jennifer Lafemina

UMass Center for Clinical and Translational Science Research Retreat

Background: Recent evidence suggests that cancer incidence among pregnant women is increasing. The pattern of malignancies in pregnant women and how these compare to their nonpregnant counterparts has not been explored. Here we describe the differences in the proportion of resected malignancies in this population. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify women aged 18-49 who underwent an operation for malignancy from 2007-2012. Age-adjusted distribution of specific surgical interventions for malignancy based on ICD-9 codes were compared among pregnant and non-pregnant women using logistic regression analysis. Results: 42,732 subjects ...


Does The Expression Of Ki-67, P16 And Cox-2 At Initial Diagnosis Of Breast Atypia Or Usual Ductal Hyperplasia Predict A Second Clinically Significant Event?, Judy A. Tjoe, Philippe Gascard, Jianxin Zhao, Gary F. Neitzel, Maharaj Singh, Brittany Last, James Marx, Thea Tlsty, Sanjay Kansra 2016 Surgical Breast Oncology, Aurora Health Care

Does The Expression Of Ki-67, P16 And Cox-2 At Initial Diagnosis Of Breast Atypia Or Usual Ductal Hyperplasia Predict A Second Clinically Significant Event?, Judy A. Tjoe, Philippe Gascard, Jianxin Zhao, Gary F. Neitzel, Maharaj Singh, Brittany Last, James Marx, Thea Tlsty, Sanjay Kansra

Maharaj Singh

Background: Women diagnosed with atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH) have a fivefold increased risk of developing breast cancer. Because ADH/ALH can be precursors or predictive markers of a subsequent clinically significant event (SCSE), i.e. atypia, in situ or invasive carcinoma, the clinical outcome for these patients ranges anywhere from remission to invasive malignancy. Currently we cannot predict which atypical breast lesion is likely to be associated with future cancer, resulting in aggressive management and, possibly, overtreatment. Kerlikowske et al. reported that a combination of three biomarkers (cell cycle regulator p16INK4a, proliferation antigen Ki-67 and ...


Pilot Study Of A Resource-Appropriate Strategy For Downstaging Breast Cancer In Rural Uganda, Alphonsus Matovu, John R. Scheel, Picho Alli Shadrack, Renny Ssembatya, Angela Njeri, Moses Galukande, Kristen K. DeStigter 2016 Mubende Regional Referral Hospital

Pilot Study Of A Resource-Appropriate Strategy For Downstaging Breast Cancer In Rural Uganda, Alphonsus Matovu, John R. Scheel, Picho Alli Shadrack, Renny Ssembatya, Angela Njeri, Moses Galukande, Kristen K. Destigter

The Journal of Global Radiology

Breast cancer incidence and mortality are rapidly increasing in low- and middle-income countries like Uganda. Shifting the proportion of women presenting with late-stage breast cancer to early-stage breast cancer (downstaging) at the time of diagnosis would substantially improve survival and efficient use of available resources. Imaging The World (ITW) conducted a pilot study in Uganda where trained village health teams (VHTs) promoted breast cancer awareness in the Kamuli District (Uganda). As a result, 212 women with self-detected lumps presented to the community health center level III (Nawanyago HCIII) for a clinical breast examination (CBE). Patients with masses on CBE were ...


Health Literacy-Listening Skill And Patient Questions Following Cancer Prevention And Screening Discussions, Kathleen M. Mazor, Donald L. Rubin, Douglas W. Roblin, Andrew E. Williams, Paul K. J. Han, Bridget Gaglio, Sarah L. Cutrona, Mary E. Costanza, Joann L. Wagner 2016 University of Massachusetts Medical School

Health Literacy-Listening Skill And Patient Questions Following Cancer Prevention And Screening Discussions, Kathleen M. Mazor, Donald L. Rubin, Douglas W. Roblin, Andrew E. Williams, Paul K. J. Han, Bridget Gaglio, Sarah L. Cutrona, Mary E. Costanza, Joann L. Wagner

Sarah L. Cutrona

OBJECTIVE: Patient question-asking is essential to shared decision making. We sought to describe patients' questions when faced with cancer prevention and screening decisions, and to explore differences in question-asking as a function of health literacy with respect to spoken information (health literacy-listening).

METHODS: Four-hundred and thirty-three (433) adults listened to simulated physician-patient interactions discussing (i) prophylactic tamoxifen for breast cancer prevention, (ii) PSA testing for prostate cancer and (iii) colorectal cancer screening, and identified questions they would have. Health literacy-listening was assessed using the Cancer Message Literacy Test-Listening (CMLT-Listening). Two authors developed a coding scheme, which was applied to all ...


Health Literacy-Listening Skill And Patient Questions Following Cancer Prevention And Screening Discussions, Kathleen M. Mazor, Donald L. Rubin, Douglas W. Roblin, Andrew E. Williams, Paul K. J. Han, Bridget Gaglio, Sarah L. Cutrona, Mary E. Costanza, Joann L. Wagner 2016 University of Massachusetts Medical School

Health Literacy-Listening Skill And Patient Questions Following Cancer Prevention And Screening Discussions, Kathleen M. Mazor, Donald L. Rubin, Douglas W. Roblin, Andrew E. Williams, Paul K. J. Han, Bridget Gaglio, Sarah L. Cutrona, Mary E. Costanza, Joann L. Wagner

Kathleen M. Mazor

OBJECTIVE: Patient question-asking is essential to shared decision making. We sought to describe patients' questions when faced with cancer prevention and screening decisions, and to explore differences in question-asking as a function of health literacy with respect to spoken information (health literacy-listening).

METHODS: Four-hundred and thirty-three (433) adults listened to simulated physician-patient interactions discussing (i) prophylactic tamoxifen for breast cancer prevention, (ii) PSA testing for prostate cancer and (iii) colorectal cancer screening, and identified questions they would have. Health literacy-listening was assessed using the Cancer Message Literacy Test-Listening (CMLT-Listening). Two authors developed a coding scheme, which was applied to all ...


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