Intake of dietary carbohydrates in early adulthood and adolescence and breast density among young women

Abstract

Purpose

Carbohydrate intake increases postprandial insulin secretion and may affect breast density, a strong risk factor for breast cancer, early in life. We examined associations of adolescent and early adulthood intakes of total carbohydrates, glycemic index/load, fiber, and simple sugars with breast density among 182 young women.

Methods

Diet was assessed using three 24-h recalls at each of five Dietary Intervention Study in Children (DISC) clinic visits when participants were age 10–19 years and at the DISC06 Follow-Up Study clinic visit when participants were age 25–29 years. Associations between energy-adjusted carbohydrates and MRI-measured percent dense breast volume (%DBV) and absolute dense breast volume (ADBV) at 25–29 years were quantified using multivariable-adjusted mixed-effects linear models.

Results

Adolescent sucrose intakes and premenarcheal total carbohydrates intakes were modestly associated with higher %DBV (mean %DBV_{Q1 vs Q4}, 16.6 vs 23.5% for sucrose; and 17.2 vs 22.3% for premenarcheal total carbohydrates, all P_trend ≤ 0.02), but not with ADBV. However, adolescent intakes of fiber and fructose were not associated with %DBV and ADBV. Early adulthood intakes of total carbohydrates, glycemic index/load, fiber, and simple sugars were not associated with %DBV and ADBV.

Conclusions

Insulinemic carbohydrate diet during puberty may be associated with adulthood breast density, but our findings need replication in larger studies. Clinical Trials Registration ClinicalTrials.gov Identifier, NCT00458588 April 9, 2007; NCT00000459 October 27, 1999

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The effect of aberrant expression and genetic polymorphisms of Rad21 on cervical cancer biology

Cancer Medicine, EarlyView.


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Therapeutic perspectives for brain metastases in non-oncogene addicted non-small cell lung cancer (NSCLC): towards a less dismal future?

Publication date: Available online 24 May 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Frega Stefano, Bonanno Laura, Guarneri Valentina, Conte Pier Franco, Pasello Giulia
Risk of brain metastases (BM) affects a remarkable number of non-small cell lung cancer (NSCLC) patients, impacting on their quality of life (QoL) and prognosis.While tyrosine-kinase inhibitors (TKIs) showed interesting intracranial control rates in oncogene-addicted NSCLC, BM still represents an unmet need for the counterpart without driver gene mutations. For these patients, new treatment options include anti-angiogenic drugs and immune-checkpoint inhibitors, possibly combined with standard chemotherapy, even though the benefit on BM has not been clearly defined. A multidisciplinary team including neurosurgeons, medical and radiation oncologists is needed in order to integrate systemic and loco-regional strategies at the right time point. Ad-hoc designed clinical trials are slowly emerging for previously treated patients with uncontrolled BM.The aim of this review is to offer a detailed and updated picture of possible approaches for non oncogene-addicted NSCLC patients having BM, in order to support clinicians in their daily practice.



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Tau mutations serve as a novel risk factor for cancer

In addition to its well-recognized role in neurodegeneration, tau participates in maintenance of genome stability and chromosome integrity. In particular, peripheral cells from patients affected by frontotemporal lobar degeneration carrying a mutation in tau gene (genetic tauopathies), as well as cells from animal models, show chromosome numerical and structural aberrations, chromatin anomalies, and a propensity toward abnormal recombination. As genome instability is tightly linked to cancer development, we hypothesized that mutated tau may be a susceptibility factor for cancer. Here we conducted a retrospective cohort study comparing cancer incidence in families affected by genetic tauopathies to control families. Additionally, we carried out a bioinformatics analysis to highlight pathways associated with the tau protein interactome. We report that the risk of developing cancer is significantly higher in families affected by genetic tauopathies, and a high proportion of tau protein interactors are involved in cellular processes particularly relevant to cancer. These findings disclose a novel role of tau as a risk factor for cancer, providing new insights in the various pathological roles of mutated tau.

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Phase 0 Trial of AZD1775 in First-Recurrence Glioblastoma Patients

Purpose: AZD1775 is a first-in-class Wee1 inhibitor with dual function as a DNA damage sensitizer and cytotoxic agent. A phase I study of AZD1775 for solid tumors suggested activity against brain tumors, but a preclinical study indicated minimal blood–brain barrier penetration in mice. To resolve this controversy, we examined the pharmacokinetics and pharmacodynamics of AZD1775 in patients with first-recurrence, glioblastoma.

Experimental Design: Twenty adult patients received a single dose of AZD1775 prior to tumor resection and enrolled in either a dose-escalation arm or a time-escalation arm. Sparse pharmacokinetic blood samples were collected, and contrast-enhancing tumor samples were collected intraoperatively. AZD1775 total and unbound concentrations were determined by a validated LC/MS-MS method. Population pharmacokinetic analysis was performed to characterize AZD1775 plasma pharmacokinetic profiles. Pharmacodynamic endpoints were compared to matched archival tissue.

Results: The AZD1775 plasma concentration–time profile following a single oral dose in patients with glioblastoma was well-described by a one-compartment model. Glomerular filtration rate was identified as a significant covariate on AZD1775 apparent clearance. AZD1775 showed good brain tumor penetration, with a median unbound tumor-to-plasma concentration ratio of 3.2, and achieved potential pharmacologically active tumor concentrations. Wee1 pathway suppression was inferred by abrogation of G₂ arrest, intensified double-strand DNA breakage, and programmed cell death. No drug-related adverse events were associated with this study.

Conclusion: In contrast to recent preclinical data, our phase 0 study of AZD 1775 in recurrent glioblastoma indicates good human brain tumor penetration, provides the first evidence of clinical biological activity in human glioblastoma, and confirms the utility of phase 0 trials as part of an accelerated paradigm for drug development in patients with glioma. Clin Cancer Res; 1–9. ©2018 AACR.

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Ad5NULL-A20 - a tropism-modified, {alpha}v{beta}6 integrin-selective oncolytic adenovirus for epithelial ovarian cancer therapies

Purpose: Virotherapies are maturing in the clinical setting. Adenoviruses (Ad) are excellent vectors for manipulability and tolerance of transgenes. Poor tumour-selectivity, off-target sequestration and immune inactivation hamper clinical efficacy. We sought to completely redesign Ad5 into a refined, tumour selective virotherapy targeted to αvβ6 integrin, which is expressed in a range of aggressively transformed epithelial cancers but non-detectable in healthy tissues. Experimental Design: Ad5_NULL-A20 harbours mutations in each major capsid protein to preclude uptake via all native pathways. Tumour-tropism via αvβ6-targeting was achieved by genetic insertion of A20 peptide (NAVPNLRGDLQVLAQKVART) within the fiber knob protein. The vector's selectivity in vitro and in vivo was assessed. Results: The tropism-ablating triple mutation completely blocked all native cell entry pathways of Ad5_NULL-A20 via coxsackie and adenovirus receptor (CAR), αvβ3/5 integrins and coagulation factor 10 (FX). Ad5_NULL-A20 efficiently and selectively transduced αvβ6+ cell lines and primary clinical ascites-derived EOC ex vivo, including in the presence of pre-existing anti-Ad5 immunity. In vivo biodistribution of Ad5_NULL-A20 following systemic delivery in non-tumour-bearing mice was significantly reduced in all off-target organs, including a remarkable 10⁷-fold reduced genome accumulation in the liver compared to Ad5. Tumour uptake, transgene expression and efficacy were confirmed in a peritoneal SKOV3 xenograft model of human EOC, where oncolytic Ad5_NULL-A20-treated animals demonstrated significantly improved survival compared to those treated with oncolytic Ad5.

Conclusions: Oncolytic Ad5_NULL-A20 virotherapies represent an excellent vector for local and systemic targeting of αvβ6-over-expressing cancers, and exciting platforms for tumour selective over-expression of therapeutic anti-cancer modalities, including immune checkpoint inhibitors.

https://ift.tt/2J16spb

Targeted Therapies for Brain Tumors: Will They Ever Deliver?

The strategy of using biologically-targeted therapeutics for cancer has yet to translate into effective treatment of gliomas. The neuro-oncology community is beginning to recognize that phase 0 studies should be performed to account for the impact of the blood-brain-barrier on the ability of a therapeutic to reach its target(s).

https://ift.tt/2s9ZrYx

Tumor elastography and its association with collagen and the tumor microenvironment.

Purpose: The tumor microenvironment presents with altered extracellular matrix (ECM) and stroma composition which may affect treatment efficacy and contribute to tissue stiffness. Ultrasound (US) elastography can visualize and quantify tissue stiffness non-invasively. However, the contributions of ECM and stroma components to stiffness are poorly understood. We therefore set out to quantify ECM and stroma density and their relation to tumor stiffness. Experimental Design: A modified clinical ultrasound system was used to measure tumor stiffness and perfusion during tumor growth in pre-clinical tumor models. In vivo measurements were compared with collagen mass spectroscopy and automatic analysis of matrix and stroma markers derived from immunofluorescence images. Results: US elastography estimates of tumor stiffness were positively correlated with tumor volume in collagen and myofibroblast-rich tumors, while no correlations were found for tumors with low collagen and myofibroblast content. US elastography measurements were strongly correlated with ex vivo mechanical testing and mass spectroscopy-based measurements of total collagen and immature collagen crosslinks. Registration of ultrasound and confocal microscopy data showed strong correlations between blood vessel density and T-cell density in syngeneic tumors, while no correlations were found for genetic tumor models. In contrast to collagen density, which was positively correlated with stiffness, no significant correlations were observed for hyaluronic acid density. Finally, localized delivery of collagenase led to a significant reduction in tumor stiffness without changes in perfusion 24 hours after treatment. Conclusions: US elastography can be used as a potential biomarker to assess changes in the tumor microenvironment, particularly changes affecting the ECM.

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An Intermediate Pluripotent State Controlled by MicroRNAs Is Required for the Naive-to-Primed Stem Cell Transition

Publication date: Available online 24 May 2018
Source:Cell Stem Cell
Author(s): Peng Du, Mehdi Pirouz, Jiho Choi, Aaron J. Huebner, Kendell Clement, Alexander Meissner, Konrad Hochedlinger, Richard I. Gregory
The embryonic stem cell (ESC) transition from naive to primed pluripotency is marked by major changes in cellular properties and developmental potential. ISY1 regulates microRNA (miRNA) biogenesis, yet its role and relevance to ESC biology remain unknown. Here, we find that highly dynamic ISY1 expression during the naive-to-primed ESC transition defines a specific phase of "poised" pluripotency characterized by distinct miRNA and mRNA transcriptomes and widespread poised cell contribution to mouse chimeras. Loss- and gain-of-function experiments reveal that ISY1 promotes exit from the naive state and is necessary and sufficient to induce and maintain poised pluripotency, and that persistent ISY1 overexpression inhibits the transition from the naive to the primed state. We identify a large subset of ISY1-dependent miRNAs that can rescue the inability of miRNA-deficient ESCs to establish the poised state and transition to the primed state. Thus, dynamic ISY1 regulates poised pluripotency through miRNAs to control ESC fate.

Graphical abstract

Teaser

Du et al. identify an intermediate "poised" pluripotent state characterized by specific mRNA and miRNA transcriptomes and the ability to contribute to mouse chimeras. ISY1-mediated miRNA regulation is necessary and sufficient for establishing poised pluripotency required for the naive-primed transition, providing an explanation for the early embryonic lethality of global miRNA deficiency.


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Exit from Naive Pluripotency Induces a Transient X Chromosome Inactivation-like State in Males

Publication date: Available online 24 May 2018
Source:Cell Stem Cell
Author(s): Elsa J. Sousa, Hannah T. Stuart, Lawrence E. Bates, Mohammadmersad Ghorbani, Jennifer Nichols, Sabine Dietmann, José C.R. Silva
A hallmark of naive pluripotency is the presence of two active X chromosomes in females. It is not clear whether prevention of X chromosome inactivation (XCI) is mediated by gene networks that preserve the naive state. Here, we show that robust naive pluripotent stem cell (nPSC) self-renewal represses expression of Xist, the master regulator of XCI. We found that nPSCs accumulate Xist on the male X chromosome and on both female X chromosomes as they become NANOG negative at the onset of differentiation. This is accompanied by the appearance of a repressive chromatin signature and partial X-linked gene silencing, suggesting a transient and rapid XCI-like state in male nPSCs. In the embryo, Xist is transiently expressed in males and in females from both X chromosomes at the onset of naive epiblast differentiation. In conclusion, we propose that XCI initiation is gender independent and triggered by destabilization of naive identity, suggesting that gender-specific mechanisms follow, rather than precede, XCI initiation.

Graphical abstract

Teaser

Silva and colleagues report that the initiation of X chromosome inactivation takes place in males and on both X chromosomes in females. This is transient and rapid and is triggered by downregulation of naive pluripotent transcription factors during the onset of differentiation.


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An ERK-Dependent Feedback Mechanism Prevents Hematopoietic Stem Cell Exhaustion

Publication date: Available online 24 May 2018
Source:Cell Stem Cell
Author(s): Christian Baumgartner, Stefanie Toifl, Matthias Farlik, Florian Halbritter, Ruth Scheicher, Irmgard Fischer, Veronika Sexl, Christoph Bock, Manuela Baccarini
Hematopoietic stem cells (HSCs) sustain hematopoiesis throughout life. HSCs exit dormancy to restore hemostasis in response to stressful events, such as acute blood loss, and must return to a quiescent state to prevent their exhaustion and resulting bone marrow failure. HSC activation is driven in part through the phosphatidylinositol 3-kinase (PI3K)/AKT/mTORC1 signaling pathway, but less is known about the cell-intrinsic pathways that control HSC dormancy. Here, we delineate an ERK-dependent, rate-limiting feedback mechanism that controls HSC fitness and their re-entry into quiescence. We show that the MEK/ERK and PI3K pathways are synchronously activated in HSCs during emergency hematopoiesis and that feedback phosphorylation of MEK1 by activated ERK counterbalances AKT/mTORC1 activation. Genetic or chemical ablation of this feedback loop tilts the balance between HSC dormancy and activation, increasing differentiated cell output and accelerating HSC exhaustion. These results suggest that MEK inhibitors developed for cancer therapy may find additional utility in controlling HSC activation.

Graphical abstract

Teaser

Baccarini and colleagues identify a cell-intrinsic feedback mechanism limiting the strength of MEK/ERK and AKT/mTORC1 signals during the activation of hematopoietic stem cells. The mechanism hinges on the negative feedback phosphorylation of MEK1 by activated ERK and is required to prevent HSC exhaustion.


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The role of the Milan System for Reporting Salivary Gland Cytopathology: A 5‐year institutional experience

Cancer Cytopathology, EarlyView.


https://ift.tt/2Ls2IeD

Association between patient‐reported hearing and visual impairments and functional, psychological, and cognitive status among older adults with cancer

Cancer, EarlyView.


https://ift.tt/2J53QGx

Retrospective self-sorted 4D-MRI for the liver

Daily MRI-guidance for liver radiotherapy is becoming possible on an MR-Linac. The purpose of this study was to develop a 4D-MRI strategy using an image-based respiratory signal with an acquisition-reconstruction time <5 min, providing T2-weighting for non-contrast enhanced tumor visibility.

https://ift.tt/2IOLdnf

Sudden cardiac arrest under spinal anesthesia in a mission hospital: a case report and review of the literature

Sudden cardiac arrest following spinal anesthesia is relatively uncommon and a matter of grave concern for any anesthesiologist as well as clinicians in general. There have been, however, several reports of su...

https://ift.tt/2koZlsI

Primary neuroendocrine carcinoma of the thymus: A retrospective analysis from a regional cancer center in Western India

Andeep Ramesh Kukkar, Harsha Panchal, Asha Anand

Indian Journal of Cancer 2017 54(3):556-559

Primary neuroendocrine tumors of the thymus are unusual anterior mediastinal tumors with a variable prognosis. A retrospective analysis of five patients with primary neuroendocrine tumors of the thymus admitted to the Gujarat Cancer and Research Institute, Ahmedabad, between 2012 and 2016, was done to study the clinical profile and outcome of these patients. The role of various prognostic factors such as surgical resection, histological grade, and Masaoka-Koga staging was also analyzed. Majority of the patients present with signs and symptoms related to a rapidly expanding mediastinal mass, such as breathlessness, facial puffiness, edema over the neck and extremities, chest pain, and other features of superior vena cava (SVC) syndrome. Collateral venous dilatation over the neck and chest and edema over neck were the most common physical signs. All the patients enrolled in the study presented in advanced stages with a poor differentiation on histopathological examination. Thymic neuroendocrine tumors usually manifest as large, lobulated, and locally invasive anterior mediastinal masses surrounding the great vessels of the neck and thorax. None of the diagnosed patients underwent surgical resection in view of extensive vascular encasement in the neck and thorax, and all of them were started on platinum-based palliative chemotherapy. The median survival of the patients was 12 months with the longest survival of 16 months for one patient. Possibility of this potentially rare entity should be kept in mind when a patient presents with features of SVC syndrome and large mediastinal mass. Complete surgical resection of the tumor is prognostic of improved treatment outcome and long-term survival. Large tumor size could be a determinant of poor overall outcome, and tumor size should strongly be considered as a factor in the revised (NETT) Neuroendocrine tumours of thymus staging. Histological grade and Masaoka-Koga stage are the important prognostic factors, but this study emphasizes the utmost need to further validate the prognostic factors.

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Papillary thyroid cancer: Why the increase and what can be done?

KP Aravindan

Indian Journal of Cancer 2017 54(3):491-492



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Radical radiotherapy for carcinoma of the larynx in the elderly: Functional and oncological outcomes from a tertiary cancer care center in India

Narayana R Subramaniam, Vijay Kumar Srinivasalu, Deepak Balasubramanian, KU Pushpaja, Anoop Remesan Nair, Chelakkot Prameela, Krishnakumar Thankappan, Subramania Iyer

Indian Journal of Cancer 2017 54(3):493-497

INTRODUCTION: It is estimated that around 10% of all head and neck cancer patients in India are aged over 70 years. Elderly patients are often subjected to palliative or inadequate treatment for head and neck cancers in spite of being candidates for curative intent therapy. In this study we evaluated our use of radical radiotherapy in carcinoma larynx for patients over seventy years of age to determine morbidity, likelihood of completing therapy, functional and oncological outcomes. MATERIALS AND METHODS: 132 patients of squamous cell carcinoma of the larynx treated between 2005-2015 at Amrita Institute of Medical Sciences, Kochi who were seventy years of age or older were included. The endpoint for analysis was overall survival. Survival curves were generated using Kaplan Meier method and univariable analysis was performed using log rank test. RESULTS: The median age of patients was 77 years (range 70-102). All patients (100%) completed radiotherapy with 6 (5%) requiring treatment breaks. All patients had at least minor (grade I/II) toxicities. Grade III toxicities were seen in 10 (8%) of patients. No grade IV reactions or treatment related deaths occurred. When a univariate analysis was performed for determinants of major toxicities with age range, performance status, smoking, number of co-morbidities or TNM stage, no determinants were statistically significant. 2-year disease free survival for stage I, II, III and IV was 100%, 98%, 80% and 64% respectively, and the 2-year overall survival for all four stages was 100%. CONCLUSION: Patients over seventy years tolerate radical radiotherapy for treatment of laryngeal cancer. In spite of minor toxicities, all patients completed treatment and had good oncological outcomes. Patients with stage III/IV unfit for concomitant chemotherapy administration treated with radiotherapy alone had a good disease free survival. Curative intent therapy should not be withheld from elderly patients on the basis of age.

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Clinicopathological spectrum of teratomas: An 8-year retrospective study from a tertiary care institute

Amit V Varma, Garima Malpani, Purti Agrawal, Kamal Malukani, Shilpi Dosi

Indian Journal of Cancer 2017 54(3):576-579

BACKGROUND: Teratomas are tumors that contain tissues derived from three different germ cell layers and having a wider range of differentiation with different site and age at presentation. The aim of the present study was to know the frequency of teratomas in various sites and to analyze their clinicomorphological features. MATERIALS AND METHODS: The present study is a retrospective study conducted in tertiary care hospital of Central India. All the cases diagnosed as teratoma in the period of 8 years were included and studied with reference to age, sex, site, size, gross, and microscopic features. RESULTS: A total of 92 cases were retrieved. The most common teratoma was ovarian (78.26%) followed by intracranial/intraspinal and sacrococcygeal in frequency of 7.61% each. Out of 92 cases, 89 were mature and benign, 2 cases were immature teratoma each in ovary and in sacrococcyx, and 1 case of teratocarcinoma in testis. CONCLUSION: Teratomas have much diversity in their age at presentation, location, gross features, and in degree of differentiation. The prognosis and treatment also depends on the histological grading of teratomas. Thus, pathologists have an important role in establishing a reliable prognostic profile.

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Prevalence of human papillomavirus in oral squamous cell carcinoma: A rural teaching hospital-based cross-sectional study

Deepa Rajesh, S M Azeem Mohiyuddin, A V Moideen Kutty, Sharath Balakrishna

Indian Journal of Cancer 2017 54(3):498-501

BACKGROUND: Human papillomavirus (HPV) is a well-established oncogenic agent in the pathogenesis of cervical carcinoma. Its role in the oncogenesis of tumors such as oral squamous cell carcinoma (OSCC) is not clear. Globally, approximately 3% of OSCCs are positive for HPV. Studies conducted in India indicate its prevalence from as low as 0% to as high as 74%. However, a recent Indian study on leukoplakia failed to find any evidence of HPV involvement. This motivated us to reexamine the HPV status in OSCC. AIM: To evaluate the prevalence of HPV in OSCC. SETTINGS AND DESIGN: This was a rural teaching hospital-based cross-sectional study. SUBJECTS AND METHODS: Sixty histopathologically confirmed samples of OSCC were used for the study. Genomic DNA was isolated from frozen, surgically-resected specimens. HPV positivity was tested by polymerase chain reaction-based method using GP5+/6+ primers in the L1 consensus region of the viral genome. RESULTS: None of the samples were HPV positive. CONCLUSIONS: Results of this study indicate that the association between HPV and OSCC may be overestimated. Hence, multicentric studies covering diverse geographical and socioeconomic groups are needed to delineate the profile of HPV infectivity and OSCC in the Indian subcontinent.

https://ift.tt/2IJchIr

Short-term efficacy and safety of apatinib in advanced squamous cell carcinoma of the lung

Xiaowu Li, Lechao Le, Liang Han, Youwei Zhang, Sanyuan Sun

Indian Journal of Cancer 2017 54(3):547-549

OBJECTIVE: To evaluate the short-term efficacy and safety of apatinib alone or combined with chemotherapy in the treatment of advanced squamous cell lung cancer. METHODS: Forty patients with advanced squamous cell lung carcinoma were enrolled in this study, who were treated in Xuzhou Central Hospital from 2014 to 2015. All patients underwent first-line or more chemotherapy. Patients were administrated with apatinib 425 mg/day, alone or combined with chemotherapy. The short-term efficacy was evaluated according to the RECIST criteria. The main safety event was evaluated by CTC-AE criteria. RESULTS: Among all the 40 patients, partial response in 5 cases, stable disease in 24 cases, progressive disease in 11 cases, overall response rate in 12.5%, disease control rate in 72.5%, the median progression-free survival was 3.7 months. The main adverse events were leukopenia, fatigue, and hypertension. Most of the adverse events were grade I and II level. CONCLUSION: The use of apatinib alone or combined with chemotherapy in patients with advanced or metastatic squamous cell lung carcinoma demonstrates a high response rate, favorable tolerability profile.

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Nasopharyngeal carcinoma: Experience and treatment outcome with radical conformal radiotherapy from a tertiary care center in India

Beena Kunheri, Gunjan Agarwal, PS Sunil, Anoop Ramesan Nair, KU Pushpaja

Indian Journal of Cancer 2017 54(3):502-507

BACKGROUND AND AIM: The majority of nasopharyngeal carcinoma (NPC) reports on the outcome and prognostic factors are from endemic high-risk regions. Data on the outcome of Indian patients are sparse. In this study, we retrospectively analyzed the outcome of NPC patients treated radically with conformal radiotherapy (RT). The primary objective was to assess the outcome, and the secondary objectives were to assess treatment-related morbidities and the impact of various prognostic factors on the outcome. MATERIALS AND METHODS: Sixty-eight patients with biopsy-proven NPC who received radical conformal RT, i.e., three-dimensional conformal RT or intensity-modulated RT (IMRT) during 2004–2013 were analyzed. All patients received conformal RT with or without chemotherapy. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS, version 20.0) software, IBM, USA. Survival analysis was performed using Kaplan–Meier method. For calculating the hazard ratio of the prognostic factors, univariate and multivariate Cox regression analyses were done. Chi-square test was used to determine the association. RESULTS: In this study, with a median follow-up of 43 months, the overall survival (OS), disease-free survival, and cause-specific survival were 91, 85.2, and 98.4% at 2 years and 78.3, 72.8, and 88.2% at 3 years, respectively. The locoregional failure was low (3%), and the 5-year cause-specific survival with chemoradiation was excellent (79%), even with 50% of the patients being nonmetastatic Stage IV. Eleven out of 12 failures were distant metastases. The treatment-related late morbidities were acceptable and better with IMRT. Significant prognostic factors affecting the outcome were composite stage of the disease and the interval between diagnosis and treatment initiation. CONCLUSION: In locally-advanced NPC, excellent local control is possible with modern conformal RT with concurrent chemotherapy. Distant metastases remain a therapeutic challenge despite systemic chemotherapy. Novel systemic therapies are needed in the future for improving the OS of these patients.

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Effect of levamisole on expression of CD138 and interleukin-6 in human multiple myeloma cell lines

B Nageshwari, Ramchander Merugu

Indian Journal of Cancer 2017 54(3):566-571

INTRODUCTION: Multiple myeloma (MM) is a B-cell malignancy accounting for 0.8% of all cancer deaths globally. This malignancy is characterized by lytic bone disease renal insufficiency, anemia, hypercalcemia, and immunodeficiency. The myeloma cells have enhanced expression of CD138. CD138 is a transmembrane heparin sulfate glycoprotein expressed on different types of adherent and nonadherent cells.CD138 is used as a standard marker for identification of tumor cells. AIMS AND OBJECTIVES: Despite introduction of many therapeutic agents, the management of multiple myeloma (MM) remains a challenge and search for new therapeutic agents is in progress. In this study, we attempted to evaluate the effect of an alkaline phosphatase inhibitor, levamisole on expression of CD138, and level of interleukin-6 (IL-6) in human MM cell lines RPMI 8226 and U266 B1. MATERIAL AND METHODS: U266B1 and RPMI 8226 cell lines were obtained from the National Centre for Cell Sciences, Pune. Alkaline phosphatase assay, Interleukin-6 assay and CD138 expression on myeloma cells by flow cytometry were investigated when the cells were exposed to Levamisole. RESULTS: Levamisole-mediated growth inhibition of myeloma cells in vitro is associated with a loss of CD138 and increased IL-6 secretion. The increased secretion of IL-6 by myeloma cells could be an attempt to protect themselves from apoptosis. CONCLUSION: Levamisole inhibited CD138 expression and affected the levels of IL-6 in a dose-dependent manner. The results of the present study add new dimension to levamisole's mode of action as inhibitor of CD138 and IL-6 and as an antiapoptotic agent.

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Magnetic resonance imaging: A predictor of pathological tumor dimensions in carcinoma of anterior two-thirds of tongue – A prospective evaluation

Sandya Chirukandath Jayasankaran, Prameela Govindalayathil Chelakkot, Milind Karippaliyil, Krishnakumar Thankappan, Subramaniya Iyer, Srikanth Moorthy

Indian Journal of Cancer 2017 54(3):508-513

INTRODUCTION: Preoperative imaging is mandatory for deciding the extent of surgery in tumors of oral tongue. Previous studies have shown the significance of depth of tumor invasion in predicting nodal involvement. AIM: This prospective study aimed to assess the correlation between tumor dimensions in all three planes obtained through preoperative imaging and histopathological findings, as well as the correlation between these and pathological node positivity. MATERIALS AND METHODS: Fifty-nine consecutive patients with nonmetastatic, operable, squamous cell carcinoma of anterior two-thirds of the tongue were included in the study. Preoperative imaging findings were compared with pathological findings and analyzed. RESULTS: Histopathological dimensions were concordant with imaging findings. Anteroposterior, transverse, and craniocaudal (CC) dimensions obtained through imaging showed a significant correlation with corresponding pathological findings (0.730, 0.621, 0.810, respectively; P < 0.001). Among all three, only CC dimension showed a significant correlation with pathological nodal involvement (odds ratio [OR] = 7.875, P = 0.03, relative risk = 0.236). Pathological tumor thickness of >3 mm had a positive predictive value of 54.9% for nodal involvement (OR = 7.875, P = 0.03). CONCLUSION: With widespread availability of state-of-the-art magnetic resonance (MR) scanners, CC dimension needs to be emphasized as the most significant prognostic tumor parameter. Recent evidence, including our study, suggests that MR imaging is concordant with pathological findings, justifying its use in the pretreatment evaluation of oral tongue lesions.

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Education differential in relation to tobacco use and its predictors across different regions of India

Deepak Sharma, Sonu Goel, Pranay Lal

Indian Journal of Cancer 2017 54(3):584-588

BACKGROUND: Tobacco use and education of an individual are linked to each other. Educated people are more likely to practice healthy behaviors and are aware of the harms of tobacco use. This paper uses the Global Adult Tobacco Survey data (GATS-India) to study the education differential associated with tobacco use and its predictors across India. METHODOLOGY: Secondary data analysis was conducted for GATS conducted in 2009–2010 in India. Data for "illiterate" and "literate" study subjects were analyzed according to study subject's "tobacco consumption pattern," their "quitting behavior," "exposure to second hand smoke (SHS)" and "observing health warnings on tobacco products." RESULTS: Tobacco smokers and smokeless tobacco users were more likely to be illiterate (odds ratio [OR] for smoking tobacco = 1.2; for smokeless tobacco = 1.5) as compared to their counterparts. Significantly, more illiterate initiated smoking tobacco (OR = 1.1; 1.02–1.26) and smokeless tobacco habit (OR = 1.3; 1.21–1.44) before 17 years of age. Illiterate people were less likely to try quitting tobacco (smoking tobacco = OR = 0.8; 0.79–0.94; smokeless tobacco = OR = 0.7; 0.70–0.81) and also less likely to think of quitting tobacco in near future (smoking tobacco = OR = 0.6; 0.59–0.71; smokeless tobacco = OR = 0.6; 0.57–0.66). Illiterate people were more likely to be exposed to SHS at home (OR = 1.8; 1.7–1.9) and less likely to notice health warnings on cigarette packets (OR = 0.2; 0.26–0.28) and smokeless tobacco pouches (unadjusted OR = 0.5; 0.49–0.53). CONCLUSION: The results confirm that education differential exists for tobacco use and its determinants in India. It is recommended that all people of our country should have access to quality education. Policy makers should target uneducated people so as to reverse the tobacco epidemic.

https://ift.tt/2ILJcYX

Clinicopathological profile of papillary carcinoma of thyroid: A 10-year experience in a tertiary care institute in North Karnataka, India

Ranjitha Rao, Sujatha S Giriyan, PK Rangappa

Indian Journal of Cancer 2017 54(3):514-518

CONTEXT: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy accounting for 80% of the thyroid cancers. Many histopathologic variants of PTC have been recognized, and few of these are of prognostic significance. The studies on clinicopathological features of PTC and its variants are so far seldom reported in India. AIM: The aim of the study was to study the percentage distribution of PTC among total thyroid specimens, the age and sex distribution of PTC, its histopathological features including frequency of nuclear findings, and various histological subtypes are also studied in detail. Methods: All cases of PTC diagnosed in our department from April 2003 to March 2013 formed the material for the study. The tissues were routinely processed and stained. On microscopic examination, tumors were classified according to 2004 WHO classification. RESULTS: PTC formed the predominant type of malignancy accounting to 71% of the total cases. Of these, about 75% of patients were in the second to fifth decade. Male to female ratio was 1:5.4. Other than the usual classic variant and follicular variant, we also found rare types such as clear cell variant, tall cell type, oncocytic type, and macrofollicular variant. Microscopically, nuclear overcrowding and ground glass nuclei were seen in more than 90% of cases. Nodular goiter, Hashimoto's thyroiditis, and follicular adenoma were associated lesions in some cases. CONCLUSION: PTC is the most common thyroid malignancy, and it can affect any age group though it presents mostly in the third to fourth decade of life. Recognition of histological subtype is crucial in patient prognosis.

https://ift.tt/2IKzMko

Axillary dissection for breast cancer using electrocautery versus ultrasonic dissectors: A prospective randomized study

Subbiah Shanmugam, Gopu Govindasamy, Syed Afroze Hussain, Prasanna Srinivasa H Rao

Indian Journal of Cancer 2017 54(3):543-546

BACKGROUND: The major morbidities of modified radical mastectomy both short- and long-term are sequelae of axillary dissection. Flap complications, prolonged seroma, need for axillary drainage, wound infection, lymphedema, shoulder stiffness, and paresthesia are major causes for morbidity after axillary dissection. Different techniques have been implemented to tackle these problems. Few of these include reducing the axillary dead space, using various forms of energy devices. AIMS: We have prospectively compared two energy sources, namely, ultrasonic dissector (UD) against the electrocautery dissection in axillary dissection for breast cancer with respect to outcomes. MATERIALS AND METHODS: One hundred female patients with breast cancer undergoing modified radical mastectomy were randomized to either of the two arms – axillary dissection using UD and axillary dissection using electrocautery. The parameters taken into consideration were operating time, operative blood loss, amount and duration of axillary drainage, flap complications, nodal yield, and postoperative pain scoring. RESULTS: There were no significant differences overall between the two groups with respect to oncological safety and functional outcomes.

https://ift.tt/2II3Gl8

Compliance and outcomes of concurrent Chemo-radiation in patients with peri-ampullary cancer undergoing curative resections

Sushmita Pathy, Supriya Mallick, Atul Sharma, Nootan K Shukla, Peush Sahni, Sujoy Pal, Suryanarayana V S Deo, Bidhu K Mohanti, Ashish Dutt Upadhyay

Indian Journal of Cancer 2017 54(3):519-525

OBJECTIVES: We aimed to study the compliance and treatment outcome of patients who received adjuvant treatment following curative resection for periampullary cancers periampullary cancers. MATERIALS AND METHODS: Institute medical records of PAC treated during 2007–2014 were retrieved. Demographics, treatment, and outcome in patients who were intended to receive adjuvant chemoradiation after curative resection were analyzed. Patients received first cycle chemotherapy with 5-fluorouracil folinic acid/capecitabine, followed by external radiotherapy 45 Gy/25 fractions/5 weeks and second and third cycle concurrent chemotherapy. Fourth and fifth cycle chemotherapy were administered after radiotherapy). Various prognostic factors, disease-free survival (DFS), and overall survival (OS) were evaluated. RESULTS: Sixty-five patients were evaluated. Median age was 50 years. 96.9% patients completed the intended course of radiation and overall adherence to chemotherapy was 86.2%. Median follow-up and DFS were 20 and 29.64 months, respectively (range: 1.9–97.3 months). Estimated 1-, 2-, 5-year DFS was 77.8%, 59.3%, and 37.6%, respectively. One-year estimated OS was 92.7%. Median DFS for node-negative and node-positive patients was 88.6 and 24.33 months (P = 0.06). Grade ≥III hematological toxicity was 20%. CONCLUSION: Positive node indicated a trend toward poor survival. The study highlights high compliance to multimodal management of PAC with acceptable toxicity in and out of clinical trial setting in a tertiary cancer center in India.

https://ift.tt/2ILJdzO

Role of laparoscopy in predicting surgical outcomes in patients undergoing interval cytoreduction surgery for advanced ovarian carcinoma: A prospective validation study

Than Singh Tomar, Rema Prabhakaran Nair, Suchetha Sambasivan, K M Jagathnath Krishna, Aleyamma Mathew, Iqbal Ahmed M

Indian Journal of Cancer 2017 54(3):550-555

OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of laparoscopy in detecting inoperable disease in patients undergoing interval cytoreduction (ICR) for advanced ovarian carcinoma (AOC). The primary outcome measured was the performance of laparoscopy-based predictive index value (PIV) score developed by Fagotti et al. The secondary outcomes measured were performance of individual parameters included in PIV score and optimal cytoreduction (OCR) rates in our population. PATIENTS AND METHODS: This is a single-arm, prospective validation trial. Patients undergoing ICR for AOC in our institution were evaluated prospectively with laparoscopy before planned attempt at debulking surgery. Seven laparoscopic parameters included in laparoscopic PIV score were evaluated. Laparoscopic findings were compared with the final outcomes of definitive surgery. OCR was defined as residual disease <1 cm. The efficiency of the individual laparoscopy score was analyzed using receiver operating characteristic (ROC) curves. RESULTS: A total of 73 patients planned for ICR for AEOC were included in the study. Laparoscopic PIV score could successfully predict inoperability in 12 (16.4% of total study population) out of 14 inoperable patients in the total population and thus could avoid 85% of unsuccessful surgeries at a PIV score cutoff of ≥8. Performance of individual parameters included in PIV score was also evaluated. Two parameters out of seven, that is, mesenteric retraction and stomach infiltration had poor performance on ROC curve. Modified PIV score was calculated for each patient after excluding these two parameters. Modified PIV score had similar performance as Fagotti's PIV score at cutoff ≥6 (P = 0.728, for difference in area under the curve). No staging laparoscopy-related serious adverse events were noted in any of the patients. CONCLUSIONS: Laparoscopy is a safe, effective, and accurate method for predicting inoperability in patients undergoing ICR for AEOC.

https://ift.tt/2xc7mdE

Advanced hepatocellular carcinoma: A regional cancer center experience of 48 cases

KN Lokesh, Tamojit Chaudhuri, KC Lakshmaiah, K Govind Babu, Lokanatha Dasappa, Linu Abraham Jacob, MC Suresh Babu, AH Rudresha, LK Rajeev

Indian Journal of Cancer 2017 54(3):526-529

BACKGROUND: Hepatocellular carcinoma (HCC) is a major health burden and the seventh most common cause of cancer-related death in India. Patients with advanced unresectable HCC have a poor prognosis with a reported median survival of only 2–3 months with the best supportive care (BSC). Sorafenib is the only drug that has demonstrated a survival benefit over BSC in advanced HCC. Unfortunately, even though it has been used for a long time, there are very few published data regarding the experience of sorafenib therapy in advanced HCC from India. MATERIALS AND METHODS: Patients diagnosed with advanced HCC from January 2012 to July 2017 at our center were reviewed retrospectively. Patients' profile, time to progression, survival, and toxicity of sorafenib therapy were evaluated. RESULTS: Of the 48 advanced patients with HCC, 35 (72.9%) were male. The median age at diagnosis was 52 years. The most common presenting symptom was abdominal pain (77%, n = 37), followed by abdominal distension (37.5%, n = 18), loss of appetite and/or weight (33.3%, n = 16), and jaundice (16.7%, n = 8). Hepatitis B virus infection was documented in 37 patients (77%), whereas 4 patients had hepatitis C virus infection. Patients were treated with standard dose sorafenib (n = 30), BSC alone (n = 14), or transarterial chemoembolization followed by sorafenib (n = 4). Sorafenib therapy was well-tolerated in most cases. The median progression-free survival with upfront sorafenib was 4.3 months. The median overall survival (OS) of the patients who received upfront sorafenib was significantly better than those treated with BSC alone (5.9 vs 3.0 months; log-rank P= 0.00). CONCLUSION: Sorafenib therapy was well-tolerated and provided about 3 months longer median OS in our patients with advanced HCC than those treated with BSC alone.

https://ift.tt/2LuIctE

Quality assessment and improvement of cancer registration system in Kamrup Urban District: A report

Arpita Sharma, Jagannath Dev Sharma, Amal Chandra Kataki, Debanjana Barman, Ranjan Lahon, Barsha Roy Deka, Chinmoy Misra, Manoj Kalita

Indian Journal of Cancer 2017 54(3):560-565

INTRODUCTION: The global burden of cancer incidence and mortality are rising continuously worldwide. As per the GLOBOCAN 2012 estimates, about 14.1 million cancer cases and 8.2 million cancer deaths occurred and 32.6 million people living with cancer (within 5 years of diagnosis) in 2012 worldwide. Reliable data on the magnitude and the pattern of cancer are essential for monitoring the health of the community, assessing the performance of the health care system. Cancer registries should pay great attention to quality of their data. The completeness of cancer registry data- the extent to which all of the incident cancers occurring in the population are included in the registry database- is an extremely important attribute of a cancer registry. There are mainly four aspects influencing the quality of data namely, comparability, completeness, validity and timeliness. MATERIALS AND METHODS: Data regarding incidence and mortality with methods of diagnosis for individual years were obtained from the National Cancer Registry Program database of the Indian Council of Medical Research for 2009 to 2014 periods and recalculated for combined years (2009-2014). RESULTS: In males in 2009-11, 77.1% were microscopically confirmed cases which are improved in the later years and for the year 2012-2014, it is 81.4%. In females also the percentage of microscopically confirmed cases were increased from 80.2% to 82.9%. An improvement in mortality to incidence ratio was observed over the years. MI ratio in males was improved to 32.9%. for the year 2012-14 as compared to 28.6% for the year 2009-11 while in female MI ratio is also increased from 18.8% to 21.8% over the period from 2009-11 to 2012-14. Whereas DCO was decreased from 12% to 10.7% in males and 7.3% to 6.6% in females respectively from the period 2009-11 to 2012-14. CONCLUSION: Although there is a slight improvement in data quality till date, there is an enormous scope for population based cancer registry Guwahati to improve the data quality.

https://ift.tt/2x8Ppwq

Nontrial, real-world outcomes in unresectable locally advanced pancreatic cancer: Chemotherapy and chemoradiation is the standard while surgery is uncommon

Anant Ramaswamy, Sunny Jandyal, Vikas Ostwal, Reena Engineer, Shirley Lewis, Subhadeep Bose, Nikhil Pande, Shailesh V Shrikhande

Indian Journal of Cancer 2017 54(3):530-534

BACKGROUND: Outcomes and survival of truly unresectable locally advanced pancreatic cancers (LAPC) is often reported along with borderline resectable pancreatic cancers especially from a real world cohort. METHODS: The audit of LAPC patients, diagnosed based on the NCCN criteria between February 2013 and January 2016 was used to identify patients starting and continuing treatment in our institution. Practice patterns, outcomes and prognostic factors for overall survival were evaluated. RESULTS: Of the 83 patients, 52 were available for inclusion in the analysis. Median age was 56 years (range 30- 77), with males constituting 75% of patients. Baseline comorbidities seen were diabetes mellitus, hypertension and cardiac dysfunction in 46.1%, 69.1% and 52% of patients respectively. 84.6% of patients had arterial vascular involvement as criteria for unresectable LAPC. 50% of patients received chemotherapy only, while the remainder received chemotherapy and concurrent chemoradiation. One patient was able to undergo curative R0 resection. FOLFIRINOX was the most commonly used chemotherapy regimen (53.8%). With a median follow up of 15.9 months, median progression free survival (mPFS) was 7.26 months (95% CI: 5.75-8.76) and median OS was 11.8 months (95% CI: 9.96 – 13.61). None of the potential prognostic factors evaluated, i.e., age, gender, nodal status, pre-treatment CA 19.9 levels, showed correlation with OS. CONCLUSION: This analysis shows outcomes in unresectable LAPC comparable to existing literature. Surgery in unresectable LAPC patients is less common than seen in previously published studies, more likely due to this cohort being truly 'unresectable' in terms of major arterial involvement.

https://ift.tt/2LqDFss

Prevalence of cytogenetic abnormalities in chronic lymphocytic leukemia in the southern part of Turkey

Emine Kilic Bagir, Arbil Acikalin, Perihan Alsancak, Semra Paydas, Emel Gurkan, Melek Ergin

Indian Journal of Cancer 2017 54(3):572-575

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia among adults in Western populations. CLL has a wide range of clinical presentations and varied outcomes. For CLL, cytogenetic assessment is essential for estimating prognoses and determining the treatment of choice. The fluorescence in situ hybridization (FISH) technique is widely used for genetic assessment due to its high sensitivity. AIM: This study aimed to evaluate the frequencies of deletions of 13q14.3, 17p13.1, 11q22.3, and 13q34 and of trisomy 12 and to observe their effects on survival in 226 Turkish CLL patients using FISH analysis. RESULT AND CONCLUSION: The frequencies of abnormalities were 65.4% for del 13q14.3, 39.8% for del 17p13.1, 19% for del 11q22.3 (del ATM), and 15.9% for trisomy 12. No patients had a 13q34.3 aberration. Our results are partially consistent with literature findings. However, certain conflicts with prior results were observed, particularly with respect to the high prevalence of 17p13.1 deletions and the enhanced survival of patients with such deletions. These inconsistencies may represent population-based differences in the genetic epidemiology of CLL.

https://ift.tt/2x8PlNc

Comparative pharmacokinetics, efficacy, and safety of bevacizumab biosimilar to reference bevacizumab in patients with metastatic colorectal cancer

Prasad Dattatray Apsangikar, Sunil Ramdev Chaudhry, Manoj Murlidhar Naik, Shashank Babarao Deoghare, Jamila Joseph

Indian Journal of Cancer 2017 54(3):535-538

OBJECTIVE: To establish clinical biosimilarity of BevaciRel™ bevacizumab biosimilar (study bevacizumab) with the reference innovator bevacizumab in terms of pharmacokinetics, efficacy, and safety in metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: A total of 119 patients with mCRC were enrolled across 20 centers and randomized to receive study and reference bevacizumab in this Phase III clinical study. Of these, 116 patients were administered bevacizumab 5 mg/kg intravenously every 2 weeks with folinic acid, fluorouracil, and irinotecan regimen. The primary endpoint of the study was objective response rate (ORR) at week 25, and the secondary endpoints assessed were progression-free survival (PFS), overall survival (OS), and assessment of pharmacokinetics and safety along with immunogenicity in both treatment arms. RESULTS: The ORR was 60.53% in study bevacizumab and 66.67% in reference arm. The proportions of subjects showing CR and PR were comparable in both the arms. The median PFS at 1 year was 3.83 months in test arm and 4.6 months in reference arm. The mean OS was 10.91 months in test arm and 14.68 months in reference arm. The difference in ORR, median PFS, and OS was not statistically significant (P > 0.05). The median Tmaxwas 6.00 h in both the arms. The median t½ was 330.63 h and 226.14 h, respectively, for test and reference bevacizumab. The adverse event profile of both products was in line with the known profile of bevacizumab. CONCLUSION: The study biosimilar bevacizumab was found to be noninferior and clinically biosimilar to the reference bevacizumab, thereby meeting an unmet medical alternative need in mCRC.

https://ift.tt/2LmGHOp

Prognostic significance of p16INK4a alteration in soft tissue sarcomas: A meta-analysis

Gang Lin, Yue Lou

Indian Journal of Cancer 2017 54(3):580-583

PURPOSE: Numerous studies have investigated the role of p16INK4a alteration in patients with soft tissue sarcomas (STSs) yielding inconsistent and inconclusive results. Hence, we conducted a meta-analysis to precisely assess its prognostic value. MATERIALS AND METHODS: Electronic literature databases such as PubMed, EMBASE, Web of Science were searched, and five studies with a total of 536 patients were eligible for this meta-analysis. Pooled hazard ratio (HR) with 95% confidence interval (95% CI) of overall survival (OS) was used to assess the prognostic role of p16INK4a alteration. RESULTS: Overall, the pooled HR for all five eligible studies evaluating decreased p16INK4a expression on OS was 1.47 (95% CI: 1.14–1.90); sensitivity analysis suggested that the pooled HR was stable and omitting a single study did not change the significance of the pooled HR. There is no evidence of publication bias in the meta-analysis. CONCLUSIONS: In conclusion, this meta-analysis showed that decreased p16INK4a expression is associated with lower OS rate in patients with STS, and it is an effective biomarker of prognosis.

https://ift.tt/2x8PhNs

T-lymphocyte profiles differ between keratoacanthomas and invasive squamous cell carcinomas of the human skin

Abstract

Background

T-lymphocytes are involved in tumor progression and regression. Actinic keratoses (AK) are atypical proliferations of keratinocytes of the skin. Some AK progress into invasive cutaneous squamous cell carcinomas (cSCC). Keratoacanthomas (KA) are either classified as a cSCC subtype or a benign tumor with histologic resemblance to well-differentiated cSCC as it is supposed to regress spontaneously. In contrast, cSCC represent malignant tumors that may metastasize.

Objectives

To compare the T-lymphocyte profiles of AK, KA and cSCC in relation to PD-L1 expression.

Methods

Tissue micro-arrays of 103 cases of AK, 43 cases of KA and 106 cases of cSCC were stained by immunohistochemistry for E-cadherin, CD3, CD4, CD8, FOXp3, and the receptor–ligand pair PD-1/PD-L1. Immunohistological scores were computationally determined to assess PD-L1 expression as well as the expression profiles of T-lymphocytes.

Results

AK had lower numbers of CD3+ and PD-1+ cells compared to KA and lower numbers of CD3+, CD8+ and PD-1+ cells in comparison with cSCC. KA showed significantly higher numbers of CD4+ and FOXp3+ cells as well as lower numbers of CD8+ cells in comparison with invasive cSCC. cSCC expressed significantly more PD-L1 in comparison with AK and KA. Among cSCC PD-L1 expression was higher in moderately and poorly-differentiated cSCC than in well-differentiated cSCC. Increased PD-L1 expression also correlated with increased numbers of CD4+, CD8+ and FOXp3+ cells in cSCC.

Conclusions

Tumor-associated T-lymphocyte infiltrates showed significant differences between AK, KA and invasive cSCC. PD-L1 expression correlated with invasion of T-cell infiltrates in invasive cSCC.

https://ift.tt/2J2ytwx

The adolescence of cancer immunotherapy: from a difficult childhood to a pillar of modern anticancer therapy

https://ift.tt/2x8yytE

Cutaneous toxicities of new treatments for melanoma

Abstract

New drugs against advanced melanoma have emerged during last decade. Target therapy and immunotherapy have changed the management of patients with metastatic disease. Along with its generalized use, drug toxicities have appeared and the skin is the target organ of a significant part of them. This revision summarizes the most common side effects and consensus management to improve the compliance of therapies and patients' quality of life. Among the BRAF inhibitors, main cutaneous side effects are photosensitivity, plantar hyperkeratosis, and the appearance of verrucal keratosis or squamous cell carcinoma. Special attention must be paid to the development of new primary melanomas or changes on nevi during BRAF inhibitor therapy. The most common cutaneous side effects of immunotherapy are rash, pruritus, and vitiligo. It remains controversial the possible role of these toxicities as markers of response to therapy.

https://ift.tt/2s9ZtzF

Can Immunotherapy Succeed in Glioblastoma?

Despite continued efforts to develop new therapies for glioblastoma, none have been able to improve how long patients live appreciably. Despite some setbacks, researchers are hopeful that immunotherapy might be able to succeed where other therapies have not.

https://ift.tt/2IYw1ar

Corrigendum to “Neoadjuvant 5-FU or Capecitabine Plus Radiation With or Without Oxaliplatin in Rectal Cancer Patients: A Phase III Randomized Clinical Trial”

Corrigendum to "Neoadjuvant 5-FU or Capecitabine Plus Radiation With or Without Oxaliplatin in Rectal Cancer Patients: A Phase III Randomized Clinical Trial" by Carmen J. Allegra et al. JNCI: J Natl Cancer Inst. 2015; 107(11): doi: 10.1093/jnci/djv248.

https://ift.tt/2sbFsd1

Correction to: Novel smac mimetic APG-1387 elicits ovarian cancer cell killing through TNF-alpha, Ripoptosome and autophagy mediated cell death pathway

In the publication of this article [1], there was an error in Figs. 2, 3 and 6.

https://ift.tt/2KQbzWh

Artesunate promotes G2/M cell cycle arrest in MCF7 breast cancer cells through ATM activation

Abstract

Background

Recent studies have revealed that artesunate (ART) has clear anti-tumor activity, suggesting that it could be a good candidate chemotherapeutic agent. In this study, we researched the inhibitory effect of ART on MCF7 cells and explored the possible mechanisms.

Methods

MTT assay was used to detect the effect of ART on the proliferation of MCF7 cells. Crystal violet staining was used to observe morphological and quantitative changes. Flow cytometry was used to detect the cell cycle of the drug-acting MCF7 cells. In addition, western blotting was used to detect the drug influence on expression of the ATM, phospho-ATM(S1981), H2AX, γH2AX(S139), CHK2 and phospho-CHK2(T68), cdc25C, and phospho-cdc25C(S216).

Results

In the experimental groups, the proliferation of MCF7 cells was inhibited in a dose-dependent manner and the original cell morphology was lost. The number of G2/M phase cells in the experimental groups increased significantly, and the expression of DNA damage response-associated proteins was significantly increased, such as phospho-ATM(S1981), γH2AX(S139), phospho-CHK2(T68), and phospho-cdc25C(S216).

Conclusions

ART can inhibit cell proliferation and promote G2/M arrest in MCF7 cells through ATM activation and the ensuing "ATM-Chk2-Cdc25C" pathway, thus implicating ART as a novel candidate for breast cancer chemotherapy.

https://ift.tt/2GNe49q

Cancers, Vol. 10, Pages 158: Beyond the Edge of Hypomethylating Agents: Novel Combination Strategies for Older Adults with Advanced MDS and AML

Cancers, Vol. 10, Pages 158: Beyond the Edge of Hypomethylating Agents: Novel Combination Strategies for Older Adults with Advanced MDS and AML

Cancers doi: 10.3390/cancers10060158

Authors: Anne Sophie Kubasch Uwe Platzbecker

Higher-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) of the elderly exhibit several commonalities, including first line treatment with hypomethylating agents (HMA) like azacitidine (AZA) or decitabine (DAC). Until today, response to treatment occurs in less than 50 percent of patients, and is often short-lived. Moreover, patients failing HMA have a dismal prognosis. Current developments include combinations of HMA with novel drugs targeting epigenetic or immunomodulatory pathways. Other efforts focus on the prevention of resistance to HMA using checkpoint inhibitors to enhance immune attack. This review focuses on recent advances in the field of HMA-based front-line therapies in elderly patients with myeloid diseases.

https://ift.tt/2J9NxIy

Cutaneous toxicities of new treatments for melanoma

Abstract

New drugs against advanced melanoma have emerged during last decade. Target therapy and immunotherapy have changed the management of patients with metastatic disease. Along with its generalized use, drug toxicities have appeared and the skin is the target organ of a significant part of them. This revision summarizes the most common side effects and consensus management to improve the compliance of therapies and patients' quality of life. Among the BRAF inhibitors, main cutaneous side effects are photosensitivity, plantar hyperkeratosis, and the appearance of verrucal keratosis or squamous cell carcinoma. Special attention must be paid to the development of new primary melanomas or changes on nevi during BRAF inhibitor therapy. The most common cutaneous side effects of immunotherapy are rash, pruritus, and vitiligo. It remains controversial the possible role of these toxicities as markers of response to therapy.

https://ift.tt/2s9ZtzF

Burnout in pediatric hematology/oncology—time to address the elephant by name

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2IJCYZm

Periocular Necrotizing Fasciitis with Toxic Shock Syndrome

Purpose: To report a case of periocular necrotizing fasciitis with toxic shock syndrome. Methods: This is a case report of a previously healthy 69-year-old woman with left preseptal eyelid infection that spread rapidly and deteriorated into necrosis of the eyelid with toxic shock syndrome. She was admitted to intensive care unit for hemodynamic stabilization. Results: Intravenous antibiotic and high-dose immunoglobulin were administered followed by surgical debridement. Rehabilitative eyelid reconstruction was performed after acute episode, resulting in patient satisfaction in relation to periocular function and appearance. Conclusion: We reported a case of periocular necrotizing fasciitis with toxic shock syndrome that necessitated early aggressive medical treatment and adequate surgical intervention to decrease morbidity and mortality. A high level of suspicion of periocular necrotizing fasciitis is necessary to make a prompt diagnosis.
Case Rep Ophthalmol 2018;9:299–303

https://ift.tt/2ILhSxN

Use of Ozone-Based Eye Drops: A Series of Cases in Veterinary and Human Spontaneous Ocular Pathologies

Conjunctivitis, keratoconjunctivitis, and corneal ulcers are common eye disorders frequently diagnosed in both humans and animals, and are currently treated by topical administration of eye drops containing anti-inflammatory and antibacterial agents. The current molecules often lack efficacy because infections in hypoxic tissue contain methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa; thus, new products for the treatment of ocular pain and inflammation are needed. The use of ozone, a molecule stabilized for topical use as an ozonide, could be providential due to its anti-inflammatory and bactericidal activity in certain anterior segment pathologies, in addition to promoting tissue repair properties. Ozonated oils have the same properties as gaseous ozone and are well tolerated by tissues. In the present study the repair and regeneration effect of ozonated oil in liposomes plus hypromellose (Ozodrop®, FB Vision, Ascoli Piceno, Italy) instilled 3–4 times a day in external ocular spontaneous pathologies both in animals and humans are reported.
Case Rep Ophthalmol 2018;9:287–298

https://ift.tt/2IJCdQ0

Retained Herrick Plug

A 79-year-old female with a history of keratoconjunctivitis sicca presented with several years of epiphora of both eyes. Thirteen years earlier, intracanalicular Herrick lacrimal plugs (Lacrimedics, Eastsound, WA, USA) had been placed in both eyes to treat her dry eye syndrome. After 13 years the patient felt the epiphora was intolerable and underwent endoscopic dacryocystorhinostomy (DCR) of the left, then the right side. Intraoperatively, during the right endoscopic DCR, a Herrick lacrimal plug was found in the common canaliculus into the lacrimal sac. Postoperatively, the patient did well with improved epiphora. The Herrick plug is designed to be intracanalicular, and this case illustrates that the plug can migrate and be retained for many years. Collared punctal plugs have a lower risk of this type of complication.
Case Rep Ophthalmol 2018;9:283–286

https://ift.tt/2Lrcyxe

Clinicopathologic Correlation of a Subretinal Proliferative Vitreoretinopathy Band in a Patient with Chronic Recurrent Retinal Detachment

Purpose: Proliferative vitreoretinopathy is a well-known cause of failure of retinal detachment surgery. The purpose of this case report is to illustrate the clinical occurrence and histopathology of a horizontal subretinal band ("clothesline" configuration) creating recurrent and persistent retinal detachment. Observations: A 67-year-old Hispanic female with diabetes type 2 and a history of retinal detachment surgery in the left eye (OS) presented with decreased vision OS. Best corrected visual acuity at this recent presentation was 20/80 OS. Clinical examination disclosed a recurrent inferior retinal detachment and a subretinal "clothesline" fibrotic band. Surgical removal of the subretinal band was performed. Histopathological evaluation of longitudinal and transverse sections of the band revealed a cable-like configuration composed predominantly of glial differentiation, RPE differentiation, and collagen, based on morphology and immunohistochemical staining. There was focal smooth muscle and neuroendocrine cell differentiation, as detected with smooth muscle actin (SMA) and S100 staining, respectively. Cross-sections demonstrated pigmented fibrocellular tissue with foci of cells staining positive for S100 and keratin peripherally around the tissue, suggestive of RPE differentiation. Scattered foci of SMA-positive cells suggested mild myoblastic differentiation. Conclusions and Importance: This case report presents further information on the structure and orientation of the cellular components of subretinal band proliferative vitreoretinopathy. Cells suggestive of Müller cell differentiation compose the central aspect of the band, alongside collagen fibers. RPE differentiation is variably present peripherally in the band, likely reflective of proliferating RPE encircling the subretinal fibrous tissue. A mild amount of myofibroblastic differentiation was present within the band of tissue, correlating with the clinical findings of subretinal tissue contraction and localized retinal detachment.
Case Rep Ophthalmol 2018;9:279–282

https://ift.tt/2IN5Xvv

Cerebral Functional Magnetic Resonance Imaging and Multifocal Visual Evoked Potentials in a Patient with Unexplained Impairment of Visual Function: A Case Report

We present a case of a young female with a slowly progressing visual impairment who was examined with multifocal visual evoked potentials and functional magnetic resonance imaging (fMRI) for underlying neuronal abnormality. The fMRI examination consisted of presenting black-and-white checkerboard stimuli, and her activation patterns were compared to the patterns from 4 normal-sighted subjects. The results showed clear differences in neuronal activation between the patient and the controls in the occipital and parietal lobes. Although we have shown neuronal correlates in a case of unexplained visual loss, it is still an open question as to whether this has an organic or functional cause, which should be the subject for future research.
Case Rep Ophthalmol 2018;9:269–278

https://ift.tt/2LpVtnq

Cataract Surgery following Sequential Myopic and Hyperopic LASIK

We report a case of patient dissatisfaction after sequential myopic and hyperopic LASIK in the same eye. We discuss the course of management for this patient involving eventual cataract extraction and intraocular lens (IOL) implantation with attention to the IOL power calculation method used.
Case Rep Ophthalmol 2018;9:264–268

https://ift.tt/2x6PII4

The change of health-related quality of life after minimally invasive esophagectomy for esophageal cancer: a meta-analysis

Abstract

Background

Short- and long-term health-related quality of life (HRQL) was severely affected after surgery. This study aimed to assess the direction and duration of HRQL from 3- to 24-month follow-ups after minimally invasive esophagectomy (MIE) for esophageal cancer.

Methods

A systematic literature search in MEDLINE, EMBASE, and the Cochrane database was performed for all potentially relevant studies published until February 2017. Studies were included if they addressed the question of HRQL with OERTC-QLQ-C30 and OES18. Primary outcomes were HRQL change at 3-month follow-up. Secondary outcomes were HRQL change from 3-, 6- (short-term) to 12- (mid-term), and/or 24-month (long-term) follow-ups.

Results

Six articles were included to estimate the change in 24 HRQL outcomes after MIE. Most of the patients' HRQL outcomes deteriorated at short-term follow-up and some lasted to mid- or long-term after MIE. Patients' physical function and global QOL deteriorated from short- to long-term follow-ups, and emotional function had no change. The directions of dyspnea, pain, fatigue, insomnia, constipation, diarrhea, cough, and speech problems were increased. The deterioration in global function lasted 6 months, the increase in constipation and speech problems lasted 12 months, and insomnia increased more than 12 months after MIE.

Conclusions

The emotional function had no change after MIE. The global QOL become worse during early postoperative period; the symptoms of constipation, speech problems, and insomnia increased for a long time after MIE.

https://ift.tt/2x9zRZq

Long noncoding RNA AFAP1-AS1 predicts a poor prognosis and regulates non–small cell lung cancer cell proliferation by epigenetically repressing p21 expression

Abstract

Background

Mounting evidence indicates that long noncoding RNAs (lncRNAs) could play a pivotal role in cancer biology. However, the role and molecular mechanism and global genes that were mediated by lncRNA AFAP1-AS1 in non–small cell lung cancer (NSCLC) remain largely unknown.

Methods

Expression of AFAP1-AS1 was analyzed in 92 NSCLC tissues and cell lines by Quantitative real time polymerase chain reaction (qRT-PCR). The effect of AFAP1-AS1 on proliferation was evaluated by function assays both in in vitro and in vivo. RNA-seq assays were performed after knockdown AFAP1-AS1. RNA immunoprecipitation (RIP) was performed to confirm the interaction between AFAP1-AS1 and EZH2. Chromatin immunoprecipitation (ChIP) was used to study the promoter region of p21.

Results

AFAP1-AS1 expression was increased in NSCLC tissues and was correlated with clinical outcomes of NSCLC. Further experiments revealed that inhibition of its expression in NSCLC cells resulted in diminished cell growth in vitro and in vivo. RNA-seq revealed that knockdown of AFAP1-AS1 could induce the expression of p21. Mechanistic investigations found that AFAP1-AS1 could interact with EZH2 and recruit EZH2 to the promoter regions of p21, thus epigenetically repressing p21 expression.

Conclusions

Together, these results suggest that lncRNA AFAP1-AS1 may serve as a candidate prognostic biomarker and target for new therapies in human NSCLC.

https://ift.tt/2s3Ii3y

Repurposing existing medications as cancer therapy: design and feasibility of a randomized pilot investigating propranolol administration in patients receiving hematopoietic cell transplantation

Abstract

Background

Repurposing existing medications for antineoplastic purposes can provide a safe, cost-effective, and efficacious means to further augment available cancer care. Clinical and preclinical studies suggest a role for the ß-adrenergic antagonist (ß-blocker) propranolol in reducing rates of tumor progression in both solid and hematologic malignancies. In patients undergoing hematopoietic cell transplantation (HCT), the peri-transplant period is a time of increased activity of the ß-adrenergically-mediated stress response.

Methods

We conducted a proof-of-concept randomized controlled pilot study assessing the feasibility of propranolol administration to patients between ages 18–75 who received an autologous HCT for multiple myeloma. Feasibility was assessed by enrollment rate, tolerability, adherence, and retention.

Results

One hundred fifty-four patients underwent screening; 31 (20%) enrolled in other oncology trials that precluded dual trial enrollment and 9 (6%) declined to enroll in the current trial. Eighty-nine (58%) did not meet eligibility requirements and 25 (16%) were eligible; of the remaining eligible patients, all were successfully enrolled and randomized. The most common reasons for ineligibility were current ß-blocker use, age, logistics, and medical contraindications. 92% of treatment arm patients tolerated and remained on propranolol for the study duration; 1 patient discontinued due to hypotension. Adherence rate in assessable patients (n = 10) was 94%. Study retention was 100%.

Conclusions

Findings show that it is feasible to recruit and treat multiple myeloma patients with propranolol during HCT, with the greatest obstacle being other competing oncology trials. These data support further studies examining propranolol and other potentially repurposed drugs in oncology populations.

Trial registration

This randomized controlled trial was registered at clinicaltrials.gov with the identifier NCT02420223 on April 17, 2015.

https://ift.tt/2GJTIOh

Endogenous H 2 S producing enzymes are involved in apoptosis induction in clear cell renal cell carcinoma

Abstract

Background

Knowledge about the expression and thus a role of enzymes that produce endogenous H₂S - cystathionine-β-synthase, cystathionine γ-lyase and mercaptopyruvate sulfurtransferase - in renal tumors is still controversial. In this study we aimed to determine the expression of these enzymes relatively to the expression in unaffected part of kidney from the same patient and to found relation of these changes to apoptosis. To evaluate patient's samples, microarray and immunohistochemistry was used.

Methods

To determine the physiological importance, we used RCC4 stable cell line derived from clear cell renal cell carcinoma, where apoptosis induction by a mixture of five chemotherapeutics with/without silencing of H₂S-producing enzymes was detected. Immunofluorescence was used to determine each enzyme in the cells.

Results

In clear cell renal cell carcinomas, expression of H₂S-producing enzymes was mostly decreased compared to a part of kidney that was distal from the tumor. To evaluate a potential role of H₂S-producing enzymes in the apoptosis induction, we used RCC4 stable cell line. We have found that silencing of cystathionine-β-synthase and cystathionine γ-lyase prevented induction of apoptosis. Immunofluorescence staining clearly showed that these enzymes were upregulated during apoptosis in RCC4 cells.

Conclusion

Based on these results we concluded that in clear cell renal cell carcinoma, reduced expression of the H₂S-producing enzymes, mainly cystathionine γ-lyase, might contribute to a resistance to the induction of apoptosis. Increased production of the endogenous H₂S, or donation from the external sources might be of a therapeutic importance in these tumors.

https://ift.tt/2LsXorq

B4GALT1 expression predicts prognosis and adjuvant chemotherapy benefits in muscle-invasive bladder cancer patients

Abstract

Background

The expression alterations of B4GALT1 have been noted in some types of cancer and they are related to cancer cell proliferation, invasiveness, metastasis, and drug resistance. We aimed to establish the expression of B4GALT1 in bladder cancer and its connection to patient outcomes, as well as forecasting the advantages of adjuvant chemotherapy (ACT) in patients with muscle-invasive bladder cancer (MIBC).

Methods

There were 142 and 112 MIBC patients who were consecutively recruited and treated via radical cystectomy from 2008 to 2012 in Shanghai Zhongshan Hospital and Fudan University Shanghai Cancer Center (FUSCC), respectively. Tissue microarrays (TMAs) were constructed in triplicate from specimens that had been fixed in formalin and embedded in paraffin samples. Immunohistochemistry was conducted to evaluate B4GALT1 expression in tumor cores, the connection between B4GALT1 expression and patients' clinical characteristics, and clinical results.

Results

B4GALT1 expression was not connected to clinical prognosis markers, but it was linked to overall survival (OS) (P = 0.013 and P = 0.010, respectively) in the two groups. Moreover, the high levels of B4GALT1 expression were independent indicators of poor OS (P = 0.026 and P = 0.046, respectively). Inclusion of B4GALT1 in the prognostic model revealed a greater predictive accuracy than the primary models. In addition, no differences were observed between B4GALT1 expression (low vs. high) and CD8+ T cell infiltration density (number/cm²) within tumor cores, but there was a positive Pearson correlation between B4GALT1 expression and expression of inhibitory receptor ligands, such as PD-L1 and CTLA4. Most significantly, the advantage of ACT noted in pT3/4 or N+ bladder cancer patients with low B4GALT1 expression was greater than in patients with a high B4GALT1 expression.

Conclusions

Our evaluation indicated that B4GALT1 may be a possible prognosticator of MIBC, and it may be a predictive marker for the choice of ACT in pT3/4 or N+ patients.

https://ift.tt/2GJZe3C

Using high throughput microtissue culture to study the difference in prostate cancer cell behavior and drug response in 2D and 3D co-cultures

Abstract

Background

There is increasing appreciation that non-cancer cells within the tumour microenvironment influence cancer progression and anti-cancer drug efficacy. For metastatic prostate cancer (PCa), the bone marrow microenvironment influences metastasis, drug response, and possibly drug resistance.

Methods

Using a novel microwell platform, the Microwell-mesh, we manufactured hundreds of 3D co-culture microtissues formed from PCa cells and bone marrow stromal cells. We used luciferase-expressing C42B PCa cells to enable quantification of the number of PCa cells in complex microtissue co-cultures. This strategy enabled us to quantify specific PCa cell growth and death in response to drug treatment, in different co-culture conditions. In parallel, we used Transwell migration assays to characterize PCa cell migration towards different 2D and 3D stromal cell populations.

Results

Our results reveal that PCa cell migration varied depending on the relative aggressiveness of the PCa cell lines, the stromal cell composition, and stromal cell 2D or 3D geometry. We found that C42B cell sensitivity to Docetaxel varied depending on culture geometry, and the presence or absence of different stromal cell populations. By contrast, the C42B cell response to Abiraterone Acetate was dependent on geometry, but not on the presence or absence of stromal cells.

Conclusion

In summary, stromal cell composition and geometry influences PCa cell migration, growth and drug response. The Microwell-mesh and microtissues are powerful tools to study these complex 3D interactions.

https://ift.tt/2J3priI

PROstate Multicentre External beam radioTHErapy Using a Stereotactic boost: the PROMETHEUS study protocol

Abstract

Background

High Dose Rate Brachytherapy (HDRB) boost is a well-established treatment for prostate cancer (PC). We describe the PROstate Multicentre External beam radioTHErapy Using Stereotactic boost (PROMETHEUS) study. Non-surgical stereotactic techniques are used to deliver similar doses to HDRB boost regimens with a dose escalation sub-study.

Methods

Eligible patients have intermediate or high risk PC. PROMETHEUS explores the safety, efficacy and feasibility of multiple Australian centres cooperating in the delivery of Prostate Stereotactic Body Radiotherapy (SBRT) technology. A SBRT boost component Target Dose (TD) of 19Gy in two fractions is to be delivered, followed by a subsequent EBRT component of 46Gy in 23 fractions. Once accrual triggers have been met, SBRT doses can be escalated in 1 Gy increments to a maximum of 22Gy in two fractions. Patient safety will also be measured with the rate of both acute and late moderate to severe Gastro-Intestinal (GI) and Genito-Urinary (GU) Common Terminology Criteria for Adverse Events (CTCAE) toxicities as well as patient reported quality of life. Efficacy will be assessed via biochemical control after 3 years.

Discussion

PROMETHEUS aims to generate evidence for a non-surgical possible future alternative to HDRB boost regimens, and introduce advanced radiotherapy techniques across multiple Australian cancer centres.

Trial registration

The study was retrospectively registered on the ANZCTR (Australian New Zealand Clinical Trials Registry) with trial ID: ACTRN12615000223538.

https://ift.tt/2KRvCnq

Role of PKM2 in directing the metabolic fate of glucose in cancer: a potential therapeutic target

Abstract

Background

Many of the hallmarks of cancer are not inherently unique to cancer, but rather represent a re-enactment of normal host responses and activities. A vivid example is aerobic glycolysis ('Warburg effect'), which is used not only by cancer cells but also by normal cells that undergo rapid proliferation. A common feature of this metabolic adaptation is a shift in the expression of pyruvate kinase (PK) isoform M1 to isoform M2. Here, we highlight the key role of PKM2 in shifting cancer metabolism between ATP production and biosynthetic processes. Since anabolic processes are highly energy dependent, the fate of glucose in energy production versus the contribution of carbon in biosynthetic processes needs to be finely synchronised. PKM2 acts to integrate cellular signalling and allosteric regulation of metabolites in order to align metabolic activities with the changing needs of the cell.

Conclusions

The central role of PKM2 in directing the flow of carbon between catabolic (ATP-producing) and anabolic processes provides unique opportunities for extending the therapeutic window of currently available and/or novel anti-neoplastic agents.

https://ift.tt/2knJBWV

Table of contents

Publication date: June 2018
Source:Cancer Epidemiology, Volume 54





https://ift.tt/2GNgMfb

Title page / Editorial Board

Publication date: June 2018
Source:Cancer Epidemiology, Volume 54





https://ift.tt/2LrOBWP

Cancers, Vol. 10, Pages 157: Reversal of Resistance in Targeted Therapy of Metastatic Melanoma: Lessons Learned from Vemurafenib (BRAFV600E-Specific Inhibitor)

Cancers, Vol. 10, Pages 157: Reversal of Resistance in Targeted Therapy of Metastatic Melanoma: Lessons Learned from Vemurafenib (BRAFV600E-Specific Inhibitor)

Cancers doi: 10.3390/cancers10060157

Authors: Antoni Xavier Torres-Collado Jeffrey Knott Ali R. Jazirehi

Malignant melanoma is the most aggressive form of skin cancer and has a very low survival rate. Over 50% of melanomas harbor various BRAF mutations with the most common being the V600E. BRAFV600E mutation that causes constitutive activation of the MAPK pathway leading to drug-, immune-resistance, apoptosis evasion, proliferation, survival, and metastasis of melanomas. The ATP competitive BRAFV600E selective inhibitor, vemurafenib, has shown dramatic success in clinical trials; promoting tumor regression and an increase in overall survival of patients with metastatic melanoma. Regrettably, vemurafenib-resistance develops over an average of six months, which renders melanomas resistant to other therapeutic strategies. Elucidation of the underlying mechanism(s) of acquisition of vemurafenib-resistance and design of novel approaches to override resistance is the subject of intense clinical and basic research. In this review, we summarize recent developments in therapeutic approaches and clinical investigations on melanomas with BRAFV600E mutation to establish a new platform for the treatment of melanoma.

https://ift.tt/2s7Rpzm

Predictive equation of metastasis in patients with malignant ovarian epithelial tumors with the Ca-125 marker

Abstract

Background

Cancer antigen (CA) 125 (CA-125) is used in ovarian cancer detection and monitoring, whose serum level has a positive correlation with tumor stage. The aim of this study was to obtain a prediction metastasis equation in a group of patients with ovarian cancer based on Ca-125.

Methods

A 2-group comparative observational study was conducted at a single oncologic institution (SOLCA) in Cuenca-Ecuador. All patients who were diagnosed with ovarian cancer between January 1996 and December 2016 were included in the current study. Group 1 (G1) patients with the I and II International Federation of Gynecology and Obstetrics (FIGO) stage and Metastasis Group (MG), with III and IV stage, were subdivided. A logistic regression equation was performed to predict metastasis based on Logarithm of serum Ca-125 levels.

Results

We included 85 cases in G1 and 64 patients in MG, with 47.8 ± 15 years (G1) and 57.5 ± 13.6 years (MG) of age (P < 0.001). Mortality in G1 was 2 cases (3.1%) and 53 cases (62.4%) in MG (P < 0.001). The CA-125 serum level was 163.5 ± 236 in G1 and 1220.9 ± 1940 u / ml in MG (P < 0.001). The equation to predict metastasis = (Age*0.053) + [(Logarithm Ca-125 value) * 1.078] − 8.163 with an OR 2.940 (CI 95% 2.046–4.223) P < 0.001. The sensitivity of the equation was 82.4% and the specificity was 79.7%.

Conclusions

It is possible to predict the presence of metastasis in a group of patients with ovarian cancer based on Ca-125.

https://ift.tt/2GIvfZT

KIBRA; a novel biomarker predicting recurrence free survival of breast cancer patients receiving adjuvant therapy

Abstract

Background

This study was carried out to evaluate the prognostic value of KIBRA in breast cancer.

Methods

This retrospective study included breast cancer patients who sought the services of the immunohistochemistry laboratory of our unit from 2006 to 2015. Tissue microarrays were constructed and immunohistochemical staining was done to assess the KIBRA expression. The Kaplan-Meier model for univariate and Cox-regression model with backward stepwise factor retention method for multivariate analyses were used. Chi square test was used to find out the associations with the established prognostic features.

Results

A total of 1124 patients were included in the study and KIBRA staining of 909 breast cancers were available for analysis. Cytoplasmic KIBRA expression was seen in 39.5% and nuclear expression in 44.8%. Overall KIBRA–low breast cancers accounted for 41.5%. KIBRA nuclear expression was significantly associated with positive ER and PR expression. Luminal breast cancer patients who had endocrine therapy and KIBRA-low expression had a RFS disadvantage over those who were positive for KIBRA (p = 0.02). Similarly, patients who received chemotherapy and had overall KIBRA-low expression also demonstrated a RFS disadvantage compared to those who had overall positive KIBRA expression (p = 0.018). This effect of KIBRA was independent of the other factors considered for the model.

Conclusion

Overall low-KIBRA expression has an independent effect on the RFS and predicts the RFS outcome of luminal breast cancer patients who received endocrine therapy and breast cancer patients who received chemotherapy.

https://ift.tt/2LrzzA5

Unusual Breast Neoplasm with Diagnostic and Management Challenges

Abstract

With the growing awareness and availability of proper screening methods, detection of breast lump is increasing globally and is now a very sensitive issue for females. The treatment of these lumps ranges from lumpectomy to wide local excision to mastectomy; hence, a proper diagnosis is very important to prevent under- or overtreatment in patients. Breast lesions are the heterogeneous diseases encompassing several distinct entities with remarkably different characteristics. While the more common forms of breast cancers are well recognized and understood better, there are many important unusual lesions and malignancies that are less known and less appreciated and can be challenging to diagnose. In such cases, due to rarity of the disease and lack of adequate treatment protocol, managing the patients can be a challenging task for surgeons and oncologist as well. In this article, we have shared our institutional experience in unusual breast lesions with emphasis on diagnostic as well as management challenges faced.

https://ift.tt/2x94GNR

The challenge of drug resistance in cancer treatment: a current overview

Abstract

It is generally accepted that recent advances in anticancer agents have contributed significantly to the improvement of both the disease-free survival and quality of life in cancer patients. However, in many instances, a favorable initial response to treatment changes afterwards, thereby leading to cancer relapse and recurrence. This phenomenon of acquired resistance to therapy, it is a major problem for totally efficient anticancer therapy. The failure to obtain an initial response reflects a form of intrinsic resistance. Specific cell membrane transporter proteins are implicated in intrinsic drug resistance by altering drug transport and pumping drugs out of the tumor cells. Moreover, the gradual acquisition of specific genetic and epigenetic abnormalities in cancer cells could contribute greatly to acquired drug resistance. A critical issue in the clinical setting, is that the problem of drug resistance appears to have a negative effect on also the new molecularly-targeted anticancer drugs. Several ongoing efforts are being made by the medical community aimed to the identification of such resistance mechanisms and the development of novel drugs that could overcome them. In this review, the major drug resistance mechanisms and strategies to overcome them are critically discussed, and also possible future directions are suggested.

https://ift.tt/2GN8CDo

Functional heterogeneity of circulating T regulatory cell subsets in breast cancer patients

Abstract

Background

Regulatory T cells (Tregs) play a major role in tumor escape from immunosurveillance by suppressing effector cells. The number of Tregs is increased in tumor sites and peripheral blood of breast cancer patients. However, the data regarding phenotypic and functional heterogeneity of Treg subpopulations in breast cancer are limited. The present study aimed to investigate the number and suppressive potential of Tregs that possess natural naïve-(N nTregs), effector/memory-like (EM nTregs), and Tr1-like phenotypes in breast cancer patients and healthy women.

Methods

The study included 10 HW and 17 primary breast cancer patients. Numbers of CD4⁺CD25⁺FoxP3⁺CD45RA⁺ N nTregs, CD4⁺CD25⁺FoxP3⁺CD45RA⁻ EM nTregs, and CD4⁺IL-4⁻IL-10⁺ Tr1 subsets and the expression of CTLA-4, CD39, GITR, LAP, and IL-35 by these Treg subsets were measured in freshly obtained peripheral blood by flow cytometry.

Results

Herein, we demonstrate that the percentages of N nTregs, EM nTregs, CD25⁺ and FoxP3⁺ Tr1 cells are elevated in the peripheral blood of breast cancer patients, but do not correlate with cancer stages. Nevertheless, the frequency of CD25⁺ Tr1 cells was associated with nodal involvement, while the number of EM nTregs correlated with clinical outcome. The expression of CTLA-4 and IL-35 by all assessed Treg subsets was increased throughout all tumor stages (I–III).

Conclusions

Collectively, the current study shows phenotypic alterations in suppressive receptors of Treg subsets, suggesting that breast cancer patients have increased activity of N nTregs, EM nTregs and Tr1 cells; and EM nTregs and CD25⁺ Tr1 cells represent prospective markers for assessing disease prognosis.

https://ift.tt/2GIplrH

Intra-arterial chemotherapy improved survival of stage 2–3 gallbladder cancer after curative resection

https://ift.tt/2IKUr3G

Expression of HSP90AA1/HSPA8 in hepatocellular carcinoma patients with depression

https://ift.tt/2s77rub

The role of HIF-1α in chemo-/radioresistant tumors

https://ift.tt/2IKUaOc

Resveratrol inhibits the proliferation of A549 cells by inhibiting the expression of COX-2

https://ift.tt/2s2xkeM

Ovol2 induces mesenchymal–epithelial transition via targeting ZEB1 in osteosarcoma

https://ift.tt/2IK0421

The methylation profiles of PRDM promoters in non–small cell lung cancer

https://ift.tt/2s3gUCM

LGR6 promotes the progression of gastric cancer through PI3K/AKT/mTOR pathway

https://ift.tt/2IKWl4m

Cancers, Vol. 10, Pages 156: Multidisciplinary Approach for Bone Metastasis: A Review

Cancers, Vol. 10, Pages 156: Multidisciplinary Approach for Bone Metastasis: A Review

Cancers doi: 10.3390/cancers10060156

Authors: Takahiro Kimura

Progress in cancer treatment has improved the survival of patients with advanced-stage cancers. Consequently, the clinical courses of patients are prolonged and often accompanied by morbidity due to bone metastases. Skeletal-related events (SREs), such as pathological fractures and spinal paralysis, cause impairment in activities of daily life and quality of life (QOL). To avoid serious SREs causing impairment in QOL and survival, early diagnosis and a prophylactic approach are required. It is necessary to initiate a bone management program concurrently with the initiation of cancer treatment to prevent complications of bone metastasis. In addition, the requirement of a multidisciplinary approach through a cancer board focusing on the management of bone metastases and involving a team of specialists in oncology, palliative care, radiotherapy, orthopedics, nuclear medicine, radiology, and physiatrists has been emphasized. In the cancer board, a strong focus is placed on the prevention of complications due to bone metastases and on reductions in the high morbidity, hospitalization rate, and overall costs associated with advanced-stage cancers. Recent reports suggest the usefulness of such approaches. The multidisciplinary approach through a cancer board would improve QOL and prognosis of patients, leading to new or continued systemic therapy for primary cancers.

https://ift.tt/2LrN9Ur

Cancers, Vol. 10, Pages 155: Targeted Tumor Therapy Remixed—An Update on the Use of Small-Molecule Drugs in Combination Therapies

Cancers, Vol. 10, Pages 155: Targeted Tumor Therapy Remixed—An Update on the Use of Small-Molecule Drugs in Combination Therapies

Cancers doi: 10.3390/cancers10060155

Authors: Martina V. Gatzka

Over the last decade, the treatment of tumor patients has been revolutionized by the highly successful introduction of novel targeted therapies, in particular small-molecule kinase inhibitors and monoclonal antibodies, as well as by immunotherapies. Depending on the mutational status, BRAF and MEK inhibitor combinations or immune checkpoint inhibitors are current first-line treatments for metastatic melanoma. However, despite great improvements of survival rates limitations due to tumor heterogeneity, primary and acquired therapy resistance, immune evasion, and economical considerations will need to be overcome. Accordingly, ongoing clinical trials explore the individualized use of small-molecule drugs in new targeted therapy combinations based on patient parameters and tumor biopsies. With focus on melanoma therapy this review aims at providing a comprehensive overview of such novel alternative and combinational therapy strategies currently emerging from basic research. The molecular principles and drug classes that may hold promise for improved tumor therapy combination regimens including kinase inhibition, induction of apoptosis, DNA-damage response inhibition, epigenetic reprogramming, telomerase inhibition, redox modulation, metabolic reprogramming, proteasome inhibition, cancer stem cell transdifferentiation, immune cell signaling modulation, and others, are explained in brief. In addition, relevant targeted therapy combinations in current clinical trials and individualized treatment strategies are highlighted.

https://ift.tt/2KSOLFF

Factors predicting intolerance to definitive conventional radiotherapy in geriatric patients

Abstract

Purpose

Although radiotherapy can be administered with a relatively low therapeutic burden, many elderly patients do not complete radiotherapy. In order to predict intolerance during radiotherapy, this study retrospectively analyzed the frequency of and risk factors for radiotherapy interruption among geriatric patients.

Methods

From September 2009 to December 2016, 353 patients aged ≥70 years received definitive radiotherapy with a conventionally fractionated schedule. "Total interruption" included completion of ≤90% of a planned radiotherapy, temporary discontinuation, and treatment-related mortality within 2 months. "Early-phase incompletion" and "mid-phase incompletion" represented completion of ≤50 and ≤80% of a planned radiotherapy, respectively.

Results

The median age of patients was 74 years. Early- and mid-phase incompletions and total interruption occurred in 4.2, 9.3, and 19.3% of patients, respectively. Total interruption occurred frequently in cancers involving the thorax (27.4%), head and neck (23.1%), abdomen (20.0%), pelvis (17.4%), and breast/extremity (8.1%). The Eastern Cooperative Oncology Group (ECOG) performance score (P = 0.004 and 0.002), serum albumin level (P = 0.016 and 0.002), and the expected 5‑year survival (P = 0.033 and 0.034) were significant factors for mid-phase incompletion and total interruption. Age ≥ 75 years (P = 0.008), concurrent chemotherapy (P = 0.017), and the extent of radiation field (P = 0.027) were factors associated with total interruption.

Conclusion

Overall, 19.3% of the elderly patients showed treatment intolerance during conventional radiotherapy. Serum albumin level and ECOG performance score should be considered as surrogate markers for radiotherapy interruption prior to the decision regarding definite conventional radiotherapy.

https://ift.tt/2IDSNEW

The hypoxic peri-arteriolar glioma stem cell niche, an integrated concept of five types of niches in human glioblastoma

Publication date: April 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1869, Issue 2
Author(s): Diana A. Aderetti, Vashendriya V.V. Hira, Remco J. Molenaar, Cornelis J.F. van Noorden
Glioblastoma is the most lethal primary brain tumor and poor survival of glioblastoma patients is attributed to the presence of glioma stem cells (GSCs). These therapy-resistant, quiescent and pluripotent cells reside in GSC niches, which are specific microenvironments that protect GSCs against radiotherapy and chemotherapy. We previously showed the existence of hypoxic peri-arteriolar GSC niches in glioblastoma tumor samples. However, other studies have described peri-vascular niches, peri-hypoxic niches, peri-immune niches and extracellular matrix niches of GSCs. The aim of this review was to critically evaluate the literature on these five different types of GSC niches. In the present review, we describe that the five niche types are not distinct from one another, but should be considered to be parts of one integral GSC niche model, the hypoxic peri-arteriolar GSC niche. Moreover, hypoxic peri-arteriolar GSC niches are structural and functional look-alikes of hematopoietic stem cell (HSC) niches in the bone marrow. GSCs are maintained in peri-arteriolar niches by the same receptor-ligand interactions as HSCs in bone marrow. Our concept should be rigidly tested in the near future and applied to develop therapies to expel and keep GSCs out of their protective niches to render them more vulnerable to standard therapies.



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