Malignant Phyllodes Tumor Presenting in Bone, Brain, Lungs, and Lymph Nodes

Introduction: Phyllodes tumors (PTs) are rare fibroepithelial tumors of the breast which are classified as benign, borderline, or malignant. Malignant PTs account for #x3c;1% of malignant breast tumors, and borderline tumors have potential to progress to malignant tumors. Metastatic recurrences are most commonly documented in bone and lungs. We report an extremely rare presentation of recurrent malignant PTs involving the brain, lung, lymph nodes, and bone. Case: A 66-year-old female presented with a large breast mass. Biopsy identified malignant PT, treated by mastectomy. One year later she presented with acute back pain; imaging showed pathological L4 spinal compression fracture. Core biopsy confirmed PT. Staging identified additional metastases in the lymph nodes, brain, and lung. Discussion: PTs are rare and fast-growing tumors that originate from periductal stromal tissues and are composed of both epithelial and stromal components. Histologically, they are classified as benign, borderline, or malignant. The prognosis of the malignant type is poorly defined, with local recurrence occurring in 10–40% and metastases in 10%. Chemotherapy and radiotherapy are generally ineffective in this tumor type. The most common metastatic sites for malignant cases are the lung and bones, but in rare instances, PTs may metastasize elsewhere. Conclusion: We report a rare presentation of recurrent malignant PT presenting as pathological fracture of the lumbar spine with impingement on the spinal column, along with cerebellar, nodal, and pulmonary metastases. Only 1 similar case has been previously reported.
Case Rep Oncol 2016;9:861–868

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A Patient with Supraclavicular Lymphadenopathy and Anterior Mediastinal Mass Presenting as a Rare Case of Composite Lymphoma: A Case Report and Literature Review

Composite lymphoma (CL) is a rare disease with 2 distinct lymphomas concurrently arising in a single patient with an estimated incidence of 1–4.7% of newly diagnosed lymphomas per year. CL most commonly involves 2 B-cell non-Hodgkin lymphomas (NHL) or a B-cell NHL with a Hodgkin lymphoma. Our case is unique in that it was a bilineage CL with both a T-cell and B-cell NHL, which has only been reported in a few case reports. A 49-year-old woman presented with several months of progressive cough, weight loss, dyspnea, and supraclavicular lymphadenopathy. Computed tomographic imaging done upon admission to the hospital found that she had extensive anterior and middle mediastinal lymphadenopathy as well as bilateral supraclavicular lymphadenopathy. The patient underwent an excisional biopsy on the supraclavicular lymph node and was found to have a composite lymphoma involving both a T-cell and B-cell NHL. Her final pathological diagnosis was peripheral T-cell lymphoma and lymphoplasmacytic lymphoma. The patient was found to have stage IIIB disease. Her HIV, hepatitis panel, and tuberculosis tests were all negative. She then underwent chemotherapy with dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab). The patient showed a complete response and was then referred to a bone marrow transplant center for an autologous hematopoietic stem cell transplant. CL is a rare disease composed of at least 2 distinct lymphomas concurrently arising in a single patient. Due to the complexity in having to treat multiple types of lymphoma simultaneously CL presents challenges with treatment and assessing prognosis.
Case Rep Oncol 2016;9:854–860

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A Case of Poorly Differentiated Large-Cell Neuroendocrine Carcinoma of the Cecum: A Rare Malignancy, with Review of the Literature

Poorly differentiated neuroendocrine carcinomas (NECs) are rare tumors that can arise anywhere along the gastrointestinal tract. They often present in advanced stage and portend a poor prognosis when compared to adenocarcinomas of the same stage. Characterization of these tumors is best accomplished with tissue biopsy, as peripheral tumor markers commonly used in NECs are of little utility. Therapeutic strategies often involve chemotherapeutic regimens that have been used to treat small-cell lung cancer. Recent studies have shown that programmed death-ligand 1 (PD-L1) expression within poorly differentiated NECs is a poor prognostic indicator. However, PD-L1 expression may represent a possible target for immunotherapy drugs, often called checkpoint inhibitors, such as anti-PD-1 inhibitors.
Case Rep Oncol 2016;9:847–853

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Use of thromboelastography in the management of liver cirrhosis and accelerated intravascular coagulation and fibrinolysis (AICF)

In the presented case, the authors describe an obese middle-aged man that presented to the emergency department for persistent oedema, scleral icterus and fatigue. He was admitted to the hospital and diagnosed with liver cirrhosis via transjugular liver biopsy. He continued to bleed from the biopsy site for 5 days from accelerated intravascular coagulation and fibrinolysis (AICF) requiring multiple transfusions of packed red blood cells, fresh-frozen plasma and cryoprecipitate. The authors then used thromboelastography (TEG) to further characterise the patient's coagulopathy, which revealed platelet inhibition. The results of the TEG significantly changed future transfusion management. Finally, the authors conducted a literature review to summarise the current literature available for the use of TEG in the management of liver cirrhosis with AICF.

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Combined central retinal vein and branch retinal artery occlusion in hyperhomocysteinaemia

Description

A woman aged 30 years reported of blurred vision in the right eye (RE) for 2 days. Visual acuity was 6/24 in the RE and 6/6 in the left eye (LE). Funduscopy of RE showed combined non-ischaemic central retinal vein occlusion (CRVO) and supero-temporal branch retinal artery occlusion (BRAO) (figure 1A). LE examination was normal. Optical coherence tomography (OCT) of the RE showed thickening of inner retinal layers corresponding to the area of BRAO (figure 1A: white arrow). Thorough systemic investigations and cardiac workup revealed raised serum homocysteine levels (37.21 μmol/L). She was started on oral folic acid and pyridoxine. Over the next 6 months, her visual acuity improved to 6/12 with clearing of retinal whitening and resolution of retinal haemorrhages (figure 1B–D).

Figure 1

Funduscopy of the right eye (RE) showing dilated torturous retinal veins with multiple retinal haemorrhages in all four quadrants...

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Iliopsoas abscess caused by chronic urolithiasis and pyelonephritis

Description

A man aged 45 years, with a history of recurrent urolithiasis and pyelonephritis, presented with a 3-month history of fever. Physical examination revealed a nodule in his right inguinal area. CT with contrast showed a right iliopsoas abscess that extended to the inguinal area and a right urethral stone (figure 1). Drainage under fluoroscopic guidance was performed, and the contrast was injected into the cavity from the drainage tube to assess the abscess cavity. The contrast study demonstrated a connection between the urethra and abscess cavity (figure 2). The patient was administered 1 g cefotiam every 8 hours. Blood, urine and fluid cultures from the abscess were positive for Escherichia coli. Surgical drainage and right nephrectomy was performed. The patient was discharged 3 months after the surgery without any complication. The penetration of an iliopsoas abscess into the urinary tract is extremely rare, while the symptoms...

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Vertical muscle transposition with silicone band belting in VI nerve palsy

A woman aged 60 years developed a Millard-Gubler syndrome after a diagnosis of a cavernous angioma in the median and paramedian areas of the pons. In this context, she presented a right VI nerve palsy, right conjugate gaze palsy, facial palsy and left hemiparesis. To improve the complete VI nerve palsy, we planned a modified transposition approach, in which procedure we made a partial transposition of vertical rectus with a silicone band that was fixated posteriorly. After the procedure, the patient gained the ability to slightly abduct the right eye. We found no compensatory torticollis in the primary position of gaze. There was also an improvement of elevation and depression movements of the right eye. We obtained satisfactory results with a theoretically reversible technique, which is adjustable intraoperatively with no need of muscle detachment, preventing anterior segment ischaemia and allowing simultaneous recession of the medial rectus muscles, if necessary.

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Short overview on the current treatment of chronic myeloid leukemia in chronic phase

Summary

This short review on current treatment options in chronic myeloid leukemia (CML) in the chronic phase summarizes the latest version of the ELN treatment recommendations dating from 2013 and indicates treatment situations not yet reflected in these recommendations. Daily practice in CML management is complicated by the recently observed treatment-emergent vascular and pulmonary adverse events in second- or later-generation tyrosine kinase inhibitors (TKIs), the lack of guidance with respect to the best TKI for initial treatment, as well as the optimal TKI sequence because no prospective randomized comparative data for second- and third-generation TKIs are available. Physicians have to balance the efficacy issues and safety aspects of the respective TKI and consider patient-specific factors such as comorbidities. Patients with any cardiovascular or pulmonary disease or treatment-requiring cardiovascular risk factor should receive nilotinib or ponatinib only if risk factors and comorbidities are treated accordingly and are further monitored. If these comorbidities are insufficiently controlled, other TKIs might be preferred. Dasatinib treatment should be critically evaluated in patients with pulmonary disease and other TKIs might be preferred in this setting. For as long as CML treatment is considered to be maintained lifelong, and no survival benefit for later-generation TKIs has been demonstrated, safety issues dominate the choice of treatment options. The concept of discontinuing TKI treatment after achieving a deep molecular response might in future change these considerations.

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Short overview on the current treatment of chronic myeloid leukemia in chronic phase

Summary

This short review on current treatment options in chronic myeloid leukemia (CML) in the chronic phase summarizes the latest version of the ELN treatment recommendations dating from 2013 and indicates treatment situations not yet reflected in these recommendations. Daily practice in CML management is complicated by the recently observed treatment-emergent vascular and pulmonary adverse events in second- or later-generation tyrosine kinase inhibitors (TKIs), the lack of guidance with respect to the best TKI for initial treatment, as well as the optimal TKI sequence because no prospective randomized comparative data for second- and third-generation TKIs are available. Physicians have to balance the efficacy issues and safety aspects of the respective TKI and consider patient-specific factors such as comorbidities. Patients with any cardiovascular or pulmonary disease or treatment-requiring cardiovascular risk factor should receive nilotinib or ponatinib only if risk factors and comorbidities are treated accordingly and are further monitored. If these comorbidities are insufficiently controlled, other TKIs might be preferred. Dasatinib treatment should be critically evaluated in patients with pulmonary disease and other TKIs might be preferred in this setting. For as long as CML treatment is considered to be maintained lifelong, and no survival benefit for later-generation TKIs has been demonstrated, safety issues dominate the choice of treatment options. The concept of discontinuing TKI treatment after achieving a deep molecular response might in future change these considerations.

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Successful treatment of mature B-cell lymphoma with rituximab-based chemotherapy in a patient with Bloom syndrome

Abstract

This report presents a case of Bloom syndrome (BS) in a consanguineous Saudi family. The patient, an 11-year-old male with mature B-cell lymphoma, had minimal therapeutic response and significant dose-limiting toxicity with standard chemotherapy treatment. He later responded successfully to a rituximab-based chemotherapy protocol. This case highlights that the rituximab-based chemotherapy protocol is an effective and safe treatment alternative for mature B-cell lymphoma in patients with BS. Further trials are warranted to investigate this modality of treatment.

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Overexpression of TEAD4 in atypical teratoid/rhabdoid tumor: New insight to the pathophysiology of an aggressive brain tumor

Abstract

Background

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant embryonal brain tumor that occurs mainly in early childhood. Although most of the tumors are characterized by inactivating mutations of the tumor suppressor gene, SMARCB1, the biological basis of its tumorigenesis and aggressiveness is still unknown.

Procedure

We performed high-throughput copy number variation analysis of primary cell lines generated from primary and relapsed tumors from one of our patients to identify new genes involved in AT/RT biology. The expression of the identified gene was validated in 29 AT/RT samples by gene expression profiling, quantitative real-time polymerase chain reaction, and immunohistochemistry (IHC). Furthermore, we investigated the function of this gene by mutating it in rhabdoid tumor cells.

Results

TEAD4 amplification was detected in the primary cell lines and its overexpression was confirmed at mRNA and protein levels in an independent cohort of AT/RT samples. TEAD4's co-activator, YAP1, and the downstream targets, MYC and CCND1, were also found to be upregulated in AT/RT when compared to medulloblastoma. IHC showed TEAD4 and YAP1 overexpression in all samples. Cell proliferation and migration were significantly reduced in TEAD4-mutated cells.

Conclusions

We report the overexpression of TEAD4 in AT/RT, which is a key component of Hippo pathway. Recent reports revealed that dysregulation of the Hippo pathway is implicated in tumorigenesis and poor prognosis of several human cancers. Our results suggest that TEAD4 plays a role in the pathophysiology of AT/RT, which represents a new insight into the biology of this aggressive tumor.

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Yield of screening echocardiograms during pediatric follow-up in survivors treated with anthracyclines and cardiotoxic radiation

Abstract

Background

Guidelines published by the Children's Oncology Group recommend screening echocardiograms for childhood cancer survivors exposed to anthracyclines and/or cardiotoxic radiation. This study aims to assess risk factors for cardiac late effects while evaluating the overall yield of screening echocardiograms.

Procedure

Demographics, exposures, and echocardiogram results were abstracted from the medical records of survivors diagnosed at ≤ 21 years old and ≥ 2 years off therapy who were exposed to anthracyclines and/or potentially cardiotoxic radiotherapy. Descriptive statistics and logistic regressions were performed and the yield of screening echocardiograms was calculated.

Results

Of 853 patients, 1,728 screening echocardiograms were performed, and 37 patients had an abnormal echocardiogram (overall yield 2.1%). Yields were only somewhat higher in more frequently screened patients. Risk factors for an abnormal result included anthracycline dose of ≥300 mg/m² (adjusted odds ratio [aOR] 3.1; 95% confidence interval [CI]: 1.3−7.2; P < 0.01) with a synergist relationship in patients who also received radiation doses ≥30 Gy (aOR 7.0; 95% CI: 1.6–31.9; P = 0.01), as well as autologous bone marrow transplant (OR 3.3; 95% CI: 1.3–8.5; P = 0.01). Sex, race, age at diagnosis, and cyclophosphamide exposure were not statistically significant risk factors, and no patient receiving <100 mg/m² anthracycline dose without concomitant radiation had an abnormal echocardiogram.

Conclusions

Dose-dependent and synergist anthracycline and cardiotoxic radiotherapy risks for developing cardiomyopathy were confirmed. However, previously identified risk factors including female sex, black race, and early age at diagnosis were not replicated in this cohort. The yields showed weak correlation across frequency categories. Echocardiographic screening recommendations for low-risk pediatric patients may warrant re-evaluation.

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Delayed elimination of high-dose methotrexate and use of carboxypeptidase G2 in pediatric patients during treatment for acute lymphoblastic leukemia

Abstract

Background

Carboxypeptidase G2 (CPDG₂) can be used as rescue treatment in cases of delayed methotrexate elimination (DME) and Mtx-induced nephrotoxicity.

Procedure

Between July 2008 and December 2014, all children (1.0–17.9 years) in the Nordic countries diagnosed with Philadelphia chromosome negative acute lymphoblastic leukemia (ALL) were treated according to the Nordic Organization for Pediatric Hematology and Oncology (NOPHO) ALL 2008 protocol, including administration of six to eight high-dose (5 g/m²/24 hr) Mtx (HDMtx) courses. The protocol includes recommendations for CPDG₂ administration in cases of DME (clinicaltrials.gov NCT01305655).

Results

Forty-seven of the 1,286 children (3.6%) received CPDG₂ during 50 HDMtx courses at a median dose of 50 IU/kg. In 49% of the cases, CPDG₂ was used during the first HDMtx course. Within a median of 6 hr from CPDG₂ administration, the Mtx concentration decreased by 75% when measured with immune-based methods, and by 100% when measured with high-performance liquid chromatography. The median time from the start of Mtx infusion to plasma levels ≤ 0.2 μM was 228 hr (range: 48–438). The maximum increase in plasma creatinine was 375% (range: 100–1,310). Creatinine peaked after a median of 48 hr (range: 36–86). Mtx elimination time was shorter in patients with body surface area < 1 m² (median 198.5 vs. 257 hr; P = 0.004) and was inversely correlated to the maximum creatinine increase (209 vs. 258 hr; P = 0.034). All patients normalized their renal function as measured with s-creatinine.

Conclusions

CPDG₂ administration is highly effective as rescue in case of delayed Mtx clearance. Subsequent HDMtx courses could be administered without events in most of the patients.

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Gene Therapy for Epidermolysis Bullosa: Sticky Business

Gene Therapy for Epidermolysis Bullosa: Sticky Business

Molecular Therapy 24, 2035 (December 2016). doi:10.1038/mt.2016.199

Authors: Alexander Nyström & Leena Bruckner-Tuderman

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Robust Oncolytic Virotherapy Induces Tumor Lysis Syndrome and Associated Toxicities in the MPC-11 Plasmacytoma Model

Robust Oncolytic Virotherapy Induces Tumor Lysis Syndrome and Associated Toxicities in the MPC-11 Plasmacytoma Model

Molecular Therapy 24, 2109 (December 2016). doi:10.1038/mt.2016.167

Authors: Lianwen Zhang, Michael B Steele, Nathan Jenks, Jacquelyn Grell, Marshall Behrens, Rebecca Nace, Shruthi Naik, Mark J Federspiel, Stephen J Russell & Kah-Whye Peng

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In This Issue

In This Issue

Molecular Therapy 24, 2037 (December 2016). doi:10.1038/mt.2016.200

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Remodeling of the Extracellular Matrix by Endothelial Cell-Targeting siRNA Improves the EPR-Based Delivery of 100 nm Particles

Remodeling of the Extracellular Matrix by Endothelial Cell-Targeting siRNA Improves the EPR-Based Delivery of 100 nm Particles

Molecular Therapy 24, 2090 (December 2016). doi:10.1038/mt.2016.178

Authors: Yu Sakurai, Tomoya Hada, Shoshiro Yamamoto, Akari Kato, Wataru Mizumura & Hideyoshi Harashima

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Research Highlights

Research Highlights

Molecular Therapy 24, 2038 (December 2016). doi:10.1038/mt.2016.201

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Corrigendum to “Targeted Delivery of C/EBPα -saRNA by Pancreatic Ductal Adenocarcinoma-specific RNA Aptamers Inhibits Tumor Growth In Vivo”

Corrigendum to "Targeted Delivery of C/EBPα -saRNA by Pancreatic Ductal Adenocarcinoma-specific RNA Aptamers Inhibits Tumor Growth In Vivo"

Molecular Therapy 24, 2131 (December 2016). doi:10.1038/mt.2016.197

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One Size Fits All?: Ethical Considerations for Examining Efficacy in First-in-Human Pluripotent Stem Cell Studies

One Size Fits All?: Ethical Considerations for Examining Efficacy in First-in-Human Pluripotent Stem Cell Studies

Molecular Therapy 24, 2039 (December 2016). doi:10.1038/mt.2016.202

Authors: Michelle GJL Habets, Johannes JM van Delden, Sophie L Niemansburg, Harold L Atkins & Annelien L Bredenoord

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Targeted Delivery of an Anti-inflammatory PDE4 Inhibitor to Immune Cells via an Antibody–drug Conjugate

Targeted Delivery of an Anti-inflammatory PDE4 Inhibitor to Immune Cells via an Antibody–drug Conjugate

Molecular Therapy 24, 2078 (December 2016). doi:10.1038/mt.2016.175

Authors: Shan Yu, Aaron D Pearson, Reyna KV Lim, David T Rodgers, Sijia Li, Holly B Parker, Meredith Weglarz, Eric N Hampton, Michael J Bollong, Jiayin Shen, Claudio Zambaldo, Danling Wang, Ashley K Woods, Timothy M Wright, Peter G Schultz, Stephanie A Kazane, Travis S Young & Matthew S Tremblay

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The Mucus Barrier to Inhaled Gene Therapy

The Mucus Barrier to Inhaled Gene Therapy

Molecular Therapy 24, 2043 (December 2016). doi:10.1038/mt.2016.182

Authors: Gregg A Duncan, James Jung, Justin Hanes & Jung Soo Suk

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The Niemann-Pick C1 Inhibitor NP3.47 Enhances Gene Silencing Potency of Lipid Nanoparticles Containing siRNA

The Niemann-Pick C1 Inhibitor NP3.47 Enhances Gene Silencing Potency of Lipid Nanoparticles Containing siRNA

Molecular Therapy 24, 2100 (December 2016). doi:10.1038/mt.2016.179

Authors: Haitang Wang, Yuen Yi C Tam, Sam Chen, Josh Zaifman, Roy van der Meel, Marco A Ciufolini & Pieter R Cullis

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Low-dose Gene Therapy Reduces the Frequency of Enzyme Replacement Therapy in a Mouse Model of Lysosomal Storage Disease

Low-dose Gene Therapy Reduces the Frequency of Enzyme Replacement Therapy in a Mouse Model of Lysosomal Storage Disease

Molecular Therapy 24, 2054 (December 2016). doi:10.1038/mt.2016.181

Authors: Marialuisa Alliegro, Rita Ferla, Edoardo Nusco, Chiara De Leonibus, Carmine Settembre & Alberto Auricchio

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Intracellular Delivery of Anti-pPKCθ (Thr538) via Protein Transduction Domain Mimics for Immunomodulation

Intracellular Delivery of Anti-pPKCθ (Thr538) via Protein Transduction Domain Mimics for Immunomodulation

Molecular Therapy 24, 2118 (December 2016). doi:10.1038/mt.2016.177

Authors: E Ilker Ozay, Gabriela Gonzalez-Perez, Joe A Torres, Jyothi Vijayaraghavan, Rebecca Lawlor, Heather L Sherman, Daniel T Garrigan, Amy S Burnside, Barbara A Osborne, Gregory N Tew & Lisa M Minter

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Linc00152 Functions as a Competing Endogenous RNA to Confer Oxaliplatin Resistance and Holds Prognostic Values in Colon Cancer

Linc00152 Functions as a Competing Endogenous RNA to Confer Oxaliplatin Resistance and Holds Prognostic Values in Colon Cancer

Molecular Therapy 24, 2064 (December 2016). doi:10.1038/mt.2016.180

Authors: Ben Yue, Donglan Cai, Chenchen Liu, Changyi Fang & Dongwang Yan

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Corrigendum to “A Self-restricted CRISPR System to Reduce Off-target Effects”

Corrigendum to "A Self-restricted CRISPR System to Reduce Off-target Effects"

Molecular Therapy 24, 2132 (December 2016). doi:10.1038/mt.2016.198

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Indian Journal of Medical and Paediatric Oncology (Indian J Med Paediatr Oncol)

EDITORIAL COMMENTARY

Classical or pylorus-preserving pancreatoduodenectomy in pancreatic and periampullary cancer: "The jury is still out!" [pg. 209]
Savio George Barreto
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

REVIEW ARTICLES

Should every patient with pancreatic cancer receive perioperative/neoadjuvant therapy? [pg. 211]
Ulrich Nitsche, Bo Kong, Alexander Balmert, Helmut Friess, Jörg Kleeff
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Skin: A mirror of internal malignancy [pg. 214]
Rita V Vora, RahulKrishna S Kota, Nilofar G Diwan, Nidhi B Jivani, Shailee S Gandhi
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Status of barium studies in the present era of oncology: Are they a history? [pg. 223]
Abhishek Mahajan, Subash Desai, Nilesh Pandurang Sable, Meenakshi Haresh Thakur
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ORIGINAL ARTICLES

Protection behaviors for cytotoxic drugs in oncology nurses of chemotherapy centers in Shiraz hospitals, South of Iran [pg. 227]
Khadijeh Abbasi, Maryam Hazrati, Abolfazl Mohammadbeigi, Jasem Ansari, Mahboubeh Sajadi, Azam Hosseinnazzhad, Esmail Moshiri
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Outcomes, cost comparison, and patient satisfaction during long-term central venous access in cancer patients: Experience from a Tertiary Care Cancer Institute in South India [pg. 232]
K Govind Babu, MC Suresh Babu, D Lokanatha, Gita R Bhat
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Effect of areca nut chewing and maximal mouth opening in schoolgoing children in Ahmedabad [pg. 239]
Azizfatema Munawer Khan, Megha S Sheth, Romsha R Purohit
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Clinicopathological features and outcomes in advanced nonsmall cell lung cancer with tailored therapy [pg. 242]
Stalin Bala, Sadashivudu Gundeti, Vijay Gandhi Linga, Lakshmi Srinivas Maddali, Raghunadha Rao Digumarti, Shantveer G Uppin
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Clinicopathological profile of gastrointestinal lymphomas in Kashmir [pg. 251]
Mehnaaz Sultan Khuroo, Summyia Farooq Khwaja, Ajaz Rather, Zhahid Hassan, Ruby Reshi, Naira Sultan Khuroo
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Metabolic toxicities in patients undergoing treatment for nonhematological malignancy: A cross-sectional study [pg. 256]
Subhash Gupta, Kunhi Parambath Haresh, Soumyajit Roy, Lakhan Kashyap, Narayan Adhikari, Rambha Pandey, Dayanand Sharma, Pramod Kumar Julka, Goura Kishor Rath
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Managing metastatic renal cell carcinoma-challenges, pitfalls, and outcomes in the real world [pg. 260]
Karnam Ashok Kumar, Gundeti Sadashivudu, KV Krishnamani, Vijay Gandhi Linga, Lakshmi Srinivas Maddali, Raghunadha Rao Digumarti
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Evaluation of thyroid lesions by fine-needle aspiration cytology based on Bethesda system for reporting thyroid cytopathology classification among the population of South Bihar [pg. 265]
Richa Bhartiya, Mahasweta Mallik, Nawanita Kumari, Brijendra Narayan Prasad
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Oxaliplatin-related neuropathy in Indian patients – no difference between generic and original molecules [pg. 271]
Bhawna Sirohi, Vikas Ostwal, Shaheenah Dawood, Gilberto Lopes, Sanjay Talole, Chaitali Nashikkar, Shailesh Shrikhande
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Burden of cervical cancer and role of screening in India [pg. 278]
Saurabh Bobdey, Jignasa Sathwara, Aanchal Jain, Ganesh Balasubramaniam
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Cognizance and utilization about breast cancer screening among the health professional female students and staffs of University Kuala Lumpur, Royal College of Medicine Perak, Malaysia [pg. 286]
ATM Emdadul Haque, Muhammad Afif Bin Mohd Hisham, Noor Azwa Laili Binti Ahmad Adzman, Nur Atiqah Binti Azudin, Nursakinah Binti Shafri, Mainul Haque
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CASE REPORTS

Juvenile granulosa cell tumor associated with Ollier disease [pg. 293]
Abhilasha Ashok Sampagar, Rahul R Jahagirdar, Vibha Sanjay Bafna, Sandip P Bartakke
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Thymoma masquerading as transfusion dependent anemia [pg. 296]
Javvid Muzamil, Aejaz Aziz Shiekh, Gull Mohammad Bhat, Abdul Rashid Lone, Shuaeb Bhat, Firdousa Nabi
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PRACTITIONER SECTION

A rare case of lung cancer presenting as an ischioanal fossa mass [pg. 300]
Nishitha Shetty, Ranvijay Singh, Maryam Naveed, Ashwini M Ronghe, Falguni Shashikant Barot
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Multiple solitary extramedullary anaplastic plasmacytomas [pg. 303]
Sandesh Madi, Vishnu Senthil, Monappa Naik, Sandeep Vijayan
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LETTERS TO EDITOR

Folate supplementation in transfusion-dependent thalassemia: Do we really need such high doses? [pg. 305]
Gaurav Tripathi, Manas Kalra, Amita Mahajan
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Early tumor shrinkage as an "on-treatment" clinical predictor of long-term outcome in solid organ cancers [pg. 306]
Pratishtha Banga Chaudhari
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Cancer risk of general people due to using joss stick for religious worshiping [pg. 307]
Beuy Joob, Viroj Wiwanitkit
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A rare case of hepatoid carcinoma of the ovary with pancytopenia and hypocellular marrow [pg. 307]
Manoj Lakhotia, Hans Raj Pahadiya, Akanksha Choudhary, Ronak Gandhi, Ramesh Chand Purohit
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Multiple cutaneous malignancies in a child with xeroderma pigmentosum: A case report [pg. 309]
Rita V Vora, RahulKrishna SureshKumar Kota, Nilofar G Diwan
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The masquerading splenic lesion [pg. 311]
Mansoor C Abdulla, Jemshad Alungal, Ram Naryan, Neena Mampilly
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ASCO 2016 GI CANCER UPDATE

Focused update on Gastrointestinal (GI) Oncology from ASCO 2016 [pg. 314]
Ravi Kumar Paluri
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ERRATUM

Erratum: Evaluation of myeloid cells (tumor associated tissue eosinophils and mast cells) infiltration in different grades of oral squamous cell carcinoma [pg. 319]

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Erratum: Isolated humeral recurrence in endometrial carcinoma [pg. 320]

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Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Successful treatment of mature B-cell lymphoma with rituximab-based chemotherapy in a patient with Bloom syndrome

Abstract

This report presents a case of Bloom syndrome (BS) in a consanguineous Saudi family. The patient, an 11-year-old male with mature B-cell lymphoma, had minimal therapeutic response and significant dose-limiting toxicity with standard chemotherapy treatment. He later responded successfully to a rituximab-based chemotherapy protocol. This case highlights that the rituximab-based chemotherapy protocol is an effective and safe treatment alternative for mature B-cell lymphoma in patients with BS. Further trials are warranted to investigate this modality of treatment.

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Research Highlights

Research Highlights

Molecular Therapy 24, 2038 (December 2016). doi:10.1038/mt.2016.201

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Overexpression of TEAD4 in atypical teratoid/rhabdoid tumor: New insight to the pathophysiology of an aggressive brain tumor

Abstract

Background

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant embryonal brain tumor that occurs mainly in early childhood. Although most of the tumors are characterized by inactivating mutations of the tumor suppressor gene, SMARCB1, the biological basis of its tumorigenesis and aggressiveness is still unknown.

Procedure

We performed high-throughput copy number variation analysis of primary cell lines generated from primary and relapsed tumors from one of our patients to identify new genes involved in AT/RT biology. The expression of the identified gene was validated in 29 AT/RT samples by gene expression profiling, quantitative real-time polymerase chain reaction, and immunohistochemistry (IHC). Furthermore, we investigated the function of this gene by mutating it in rhabdoid tumor cells.

Results

TEAD4 amplification was detected in the primary cell lines and its overexpression was confirmed at mRNA and protein levels in an independent cohort of AT/RT samples. TEAD4's co-activator, YAP1, and the downstream targets, MYC and CCND1, were also found to be upregulated in AT/RT when compared to medulloblastoma. IHC showed TEAD4 and YAP1 overexpression in all samples. Cell proliferation and migration were significantly reduced in TEAD4-mutated cells.

Conclusions

We report the overexpression of TEAD4 in AT/RT, which is a key component of Hippo pathway. Recent reports revealed that dysregulation of the Hippo pathway is implicated in tumorigenesis and poor prognosis of several human cancers. Our results suggest that TEAD4 plays a role in the pathophysiology of AT/RT, which represents a new insight into the biology of this aggressive tumor.

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Yield of screening echocardiograms during pediatric follow-up in survivors treated with anthracyclines and cardiotoxic radiation

Abstract

Background

Guidelines published by the Children's Oncology Group recommend screening echocardiograms for childhood cancer survivors exposed to anthracyclines and/or cardiotoxic radiation. This study aims to assess risk factors for cardiac late effects while evaluating the overall yield of screening echocardiograms.

Procedure

Demographics, exposures, and echocardiogram results were abstracted from the medical records of survivors diagnosed at ≤ 21 years old and ≥ 2 years off therapy who were exposed to anthracyclines and/or potentially cardiotoxic radiotherapy. Descriptive statistics and logistic regressions were performed and the yield of screening echocardiograms was calculated.

Results

Of 853 patients, 1,728 screening echocardiograms were performed, and 37 patients had an abnormal echocardiogram (overall yield 2.1%). Yields were only somewhat higher in more frequently screened patients. Risk factors for an abnormal result included anthracycline dose of ≥300 mg/m² (adjusted odds ratio [aOR] 3.1; 95% confidence interval [CI]: 1.3−7.2; P < 0.01) with a synergist relationship in patients who also received radiation doses ≥30 Gy (aOR 7.0; 95% CI: 1.6–31.9; P = 0.01), as well as autologous bone marrow transplant (OR 3.3; 95% CI: 1.3–8.5; P = 0.01). Sex, race, age at diagnosis, and cyclophosphamide exposure were not statistically significant risk factors, and no patient receiving <100 mg/m² anthracycline dose without concomitant radiation had an abnormal echocardiogram.

Conclusions

Dose-dependent and synergist anthracycline and cardiotoxic radiotherapy risks for developing cardiomyopathy were confirmed. However, previously identified risk factors including female sex, black race, and early age at diagnosis were not replicated in this cohort. The yields showed weak correlation across frequency categories. Echocardiographic screening recommendations for low-risk pediatric patients may warrant re-evaluation.

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Delayed elimination of high-dose methotrexate and use of carboxypeptidase G2 in pediatric patients during treatment for acute lymphoblastic leukemia

Abstract

Background

Carboxypeptidase G2 (CPDG₂) can be used as rescue treatment in cases of delayed methotrexate elimination (DME) and Mtx-induced nephrotoxicity.

Procedure

Between July 2008 and December 2014, all children (1.0–17.9 years) in the Nordic countries diagnosed with Philadelphia chromosome negative acute lymphoblastic leukemia (ALL) were treated according to the Nordic Organization for Pediatric Hematology and Oncology (NOPHO) ALL 2008 protocol, including administration of six to eight high-dose (5 g/m²/24 hr) Mtx (HDMtx) courses. The protocol includes recommendations for CPDG₂ administration in cases of DME (clinicaltrials.gov NCT01305655).

Results

Forty-seven of the 1,286 children (3.6%) received CPDG₂ during 50 HDMtx courses at a median dose of 50 IU/kg. In 49% of the cases, CPDG₂ was used during the first HDMtx course. Within a median of 6 hr from CPDG₂ administration, the Mtx concentration decreased by 75% when measured with immune-based methods, and by 100% when measured with high-performance liquid chromatography. The median time from the start of Mtx infusion to plasma levels ≤ 0.2 μM was 228 hr (range: 48–438). The maximum increase in plasma creatinine was 375% (range: 100–1,310). Creatinine peaked after a median of 48 hr (range: 36–86). Mtx elimination time was shorter in patients with body surface area < 1 m² (median 198.5 vs. 257 hr; P = 0.004) and was inversely correlated to the maximum creatinine increase (209 vs. 258 hr; P = 0.034). All patients normalized their renal function as measured with s-creatinine.

Conclusions

CPDG₂ administration is highly effective as rescue in case of delayed Mtx clearance. Subsequent HDMtx courses could be administered without events in most of the patients.

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Gene Therapy for Epidermolysis Bullosa: Sticky Business

Gene Therapy for Epidermolysis Bullosa: Sticky Business

Molecular Therapy 24, 2035 (December 2016). doi:10.1038/mt.2016.199

Authors: Alexander Nyström & Leena Bruckner-Tuderman

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Robust Oncolytic Virotherapy Induces Tumor Lysis Syndrome and Associated Toxicities in the MPC-11 Plasmacytoma Model

Robust Oncolytic Virotherapy Induces Tumor Lysis Syndrome and Associated Toxicities in the MPC-11 Plasmacytoma Model

Molecular Therapy 24, 2109 (December 2016). doi:10.1038/mt.2016.167

Authors: Lianwen Zhang, Michael B Steele, Nathan Jenks, Jacquelyn Grell, Marshall Behrens, Rebecca Nace, Shruthi Naik, Mark J Federspiel, Stephen J Russell & Kah-Whye Peng

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In This Issue

In This Issue

Molecular Therapy 24, 2037 (December 2016). doi:10.1038/mt.2016.200

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Remodeling of the Extracellular Matrix by Endothelial Cell-Targeting siRNA Improves the EPR-Based Delivery of 100 nm Particles

Remodeling of the Extracellular Matrix by Endothelial Cell-Targeting siRNA Improves the EPR-Based Delivery of 100 nm Particles

Molecular Therapy 24, 2090 (December 2016). doi:10.1038/mt.2016.178

Authors: Yu Sakurai, Tomoya Hada, Shoshiro Yamamoto, Akari Kato, Wataru Mizumura & Hideyoshi Harashima

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Corrigendum to “Targeted Delivery of C/EBPα -saRNA by Pancreatic Ductal Adenocarcinoma-specific RNA Aptamers Inhibits Tumor Growth In Vivo”

Corrigendum to "Targeted Delivery of C/EBPα -saRNA by Pancreatic Ductal Adenocarcinoma-specific RNA Aptamers Inhibits Tumor Growth In Vivo"

Molecular Therapy 24, 2131 (December 2016). doi:10.1038/mt.2016.197

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One Size Fits All?: Ethical Considerations for Examining Efficacy in First-in-Human Pluripotent Stem Cell Studies

One Size Fits All?: Ethical Considerations for Examining Efficacy in First-in-Human Pluripotent Stem Cell Studies

Molecular Therapy 24, 2039 (December 2016). doi:10.1038/mt.2016.202

Authors: Michelle GJL Habets, Johannes JM van Delden, Sophie L Niemansburg, Harold L Atkins & Annelien L Bredenoord

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Targeted Delivery of an Anti-inflammatory PDE4 Inhibitor to Immune Cells via an Antibody–drug Conjugate

Targeted Delivery of an Anti-inflammatory PDE4 Inhibitor to Immune Cells via an Antibody–drug Conjugate

Molecular Therapy 24, 2078 (December 2016). doi:10.1038/mt.2016.175

Authors: Shan Yu, Aaron D Pearson, Reyna KV Lim, David T Rodgers, Sijia Li, Holly B Parker, Meredith Weglarz, Eric N Hampton, Michael J Bollong, Jiayin Shen, Claudio Zambaldo, Danling Wang, Ashley K Woods, Timothy M Wright, Peter G Schultz, Stephanie A Kazane, Travis S Young & Matthew S Tremblay

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The Mucus Barrier to Inhaled Gene Therapy

The Mucus Barrier to Inhaled Gene Therapy

Molecular Therapy 24, 2043 (December 2016). doi:10.1038/mt.2016.182

Authors: Gregg A Duncan, James Jung, Justin Hanes & Jung Soo Suk

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The Niemann-Pick C1 Inhibitor NP3.47 Enhances Gene Silencing Potency of Lipid Nanoparticles Containing siRNA

The Niemann-Pick C1 Inhibitor NP3.47 Enhances Gene Silencing Potency of Lipid Nanoparticles Containing siRNA

Molecular Therapy 24, 2100 (December 2016). doi:10.1038/mt.2016.179

Authors: Haitang Wang, Yuen Yi C Tam, Sam Chen, Josh Zaifman, Roy van der Meel, Marco A Ciufolini & Pieter R Cullis

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Low-dose Gene Therapy Reduces the Frequency of Enzyme Replacement Therapy in a Mouse Model of Lysosomal Storage Disease

Low-dose Gene Therapy Reduces the Frequency of Enzyme Replacement Therapy in a Mouse Model of Lysosomal Storage Disease

Molecular Therapy 24, 2054 (December 2016). doi:10.1038/mt.2016.181

Authors: Marialuisa Alliegro, Rita Ferla, Edoardo Nusco, Chiara De Leonibus, Carmine Settembre & Alberto Auricchio

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Intracellular Delivery of Anti-pPKCθ (Thr538) via Protein Transduction Domain Mimics for Immunomodulation

Intracellular Delivery of Anti-pPKCθ (Thr538) via Protein Transduction Domain Mimics for Immunomodulation

Molecular Therapy 24, 2118 (December 2016). doi:10.1038/mt.2016.177

Authors: E Ilker Ozay, Gabriela Gonzalez-Perez, Joe A Torres, Jyothi Vijayaraghavan, Rebecca Lawlor, Heather L Sherman, Daniel T Garrigan, Amy S Burnside, Barbara A Osborne, Gregory N Tew & Lisa M Minter

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Linc00152 Functions as a Competing Endogenous RNA to Confer Oxaliplatin Resistance and Holds Prognostic Values in Colon Cancer

Linc00152 Functions as a Competing Endogenous RNA to Confer Oxaliplatin Resistance and Holds Prognostic Values in Colon Cancer

Molecular Therapy 24, 2064 (December 2016). doi:10.1038/mt.2016.180

Authors: Ben Yue, Donglan Cai, Chenchen Liu, Changyi Fang & Dongwang Yan

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Corrigendum to “A Self-restricted CRISPR System to Reduce Off-target Effects”

Corrigendum to "A Self-restricted CRISPR System to Reduce Off-target Effects"

Molecular Therapy 24, 2132 (December 2016). doi:10.1038/mt.2016.198

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