Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Diana Oelofse, Ilse Truter
BackgroundThe incidence of haematological malignancies in Africa's rapidly urbanising populations is insufficiently explored. Reliable population-based cancer statistics, however, continues to be a scarce resource in Africa and tends to be urban biased with limited rural coverage. In addition, many haematological malignancies are regarded as rare cancers, a sub-group that often affects the young disproportionately and require advanced diagnostic services and facilities able to deliver costly sophisticated treatments. This study provides a first attempt to estimate the incidence of haematological malignancies among the Eastern Cape Province population of South Africa.MethodMultiple public- and private sector data archives and resources were utilised to optimise the identification of incident cases, including clinical records; bone marrow; cytology; histology; flow cytometry and cytogenetic records. Crude incidence, age-and gender-standardised rates are presented and comparison made with existing national data and select data from other economically developed countries and global institutions.ResultsA total of 3603 incident cases were identified between 2004 and 2013. Mature lymphoid malignancies accounted for approximately 60% (n = 2153), myeloma/plasma cell neoplasms 13% (n = 465), acute leukaemia 17% (n = 596), chronic myeloid leukaemia 4% (n = 155) and other myeloproliferative neoplasms 6% (n = 234) when stratified according to conventional groups. Most subtypes increase with age, with male excess.ConclusionHaematological malignancies in the Eastern Cape Province show disparities in gender and pathology-specific incidence patterns. The present study suggest that haematological malignancies are not uncommon in this region and the incidence rate of at least one rare subtype, APL, is comparable with some European populations.
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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Σάββατο 17 Φεβρουαρίου 2018
Incidence of haematological malignancies, Eastern Cape Province; South Africa, 2004–2013
Incidence of haematological malignancies, Eastern Cape Province; South Africa, 2004–2013
Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Diana Oelofse, Ilse Truter
BackgroundThe incidence of haematological malignancies in Africa's rapidly urbanising populations is insufficiently explored. Reliable population-based cancer statistics, however, continues to be a scarce resource in Africa and tends to be urban biased with limited rural coverage. In addition, many haematological malignancies are regarded as rare cancers, a sub-group that often affects the young disproportionately and require advanced diagnostic services and facilities able to deliver costly sophisticated treatments. This study provides a first attempt to estimate the incidence of haematological malignancies among the Eastern Cape Province population of South Africa.MethodMultiple public- and private sector data archives and resources were utilised to optimise the identification of incident cases, including clinical records; bone marrow; cytology; histology; flow cytometry and cytogenetic records. Crude incidence, age-and gender-standardised rates are presented and comparison made with existing national data and select data from other economically developed countries and global institutions.ResultsA total of 3603 incident cases were identified between 2004 and 2013. Mature lymphoid malignancies accounted for approximately 60% (n = 2153), myeloma/plasma cell neoplasms 13% (n = 465), acute leukaemia 17% (n = 596), chronic myeloid leukaemia 4% (n = 155) and other myeloproliferative neoplasms 6% (n = 234) when stratified according to conventional groups. Most subtypes increase with age, with male excess.ConclusionHaematological malignancies in the Eastern Cape Province show disparities in gender and pathology-specific incidence patterns. The present study suggest that haematological malignancies are not uncommon in this region and the incidence rate of at least one rare subtype, APL, is comparable with some European populations.
http://ift.tt/2CsXbyw
Insulin-like growth factor 2: a poor prognostic biomarker linked to racial disparity in women with uterine carcinosarcoma
Abstract
The objective of this study was to investigate the relationship of insulin-like growth factor 2 (IGF2) expression and survival in women with uterine carcinosarcoma (UCS). Insulin-like growth factor 2 protein expression was determined by immunohistochemical staining of tumor tissues from 103 patients with UCS. The H-score (product of staining intensity and percentage positive cells) was quantified for the epithelial cytoplasmic (EC), epithelial nuclear (EN), and malignant stromal compartments. Multivariable Cox proportional hazard regression models were used to examine the relationship of IGF2 levels with progression-free survival (PFS) and overall survival (OS). Adjusting for stage, race, and adjuvant therapy, PFS and OS were reduced in patients with high IGF2 (H-score ≥ median) in the EC and EN compartments. Black race was independently associated with reduced PFS and OS in patients with early-stage disease, and IGF2 levels in the EC were higher in black than in white patients (P = 0.02, Wilcoxon test). In a race-stratified multivariable analysis, high IGF2 in the epithelial compartments more than doubled the risk of death in black women; HR = 2.43 (95% CI: 1.18–5.01, P = 0.02) for high IGF2 in the EC; and HR = 2.34 (95% CI: 1.25–4.39, P = 0.008) for high IGF2 in the EN. In conclusion, high tumor IGF2 expression is an independent risk factor for reduced PFS and OS in UCS. Black women have elevated tumor IGF2 compared with white women, and decreased survival associated with high IGF2. These findings identify IGF2 as a candidate biomarker for survival linked to racial disparity in women with UCS.
This study shows that IGF2 protein expression is an independent poor prognostic biomarker in uterine carcinosarcoma, a lethal uterine cancer that disproportionately impacts black women. These novel findings suggest that IGF2 is a biological mediator of an aggressive cancer phenotype and a potential therapeutic target in this disease. Moreover, we have uncovered an intriguing association of IGF2 with racial disparity in uterine carcinosarcoma survival.
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Insulin-like growth factor 2: a poor prognostic biomarker linked to racial disparity in women with uterine carcinosarcoma
Abstract
The objective of this study was to investigate the relationship of insulin-like growth factor 2 (IGF2) expression and survival in women with uterine carcinosarcoma (UCS). Insulin-like growth factor 2 protein expression was determined by immunohistochemical staining of tumor tissues from 103 patients with UCS. The H-score (product of staining intensity and percentage positive cells) was quantified for the epithelial cytoplasmic (EC), epithelial nuclear (EN), and malignant stromal compartments. Multivariable Cox proportional hazard regression models were used to examine the relationship of IGF2 levels with progression-free survival (PFS) and overall survival (OS). Adjusting for stage, race, and adjuvant therapy, PFS and OS were reduced in patients with high IGF2 (H-score ≥ median) in the EC and EN compartments. Black race was independently associated with reduced PFS and OS in patients with early-stage disease, and IGF2 levels in the EC were higher in black than in white patients (P = 0.02, Wilcoxon test). In a race-stratified multivariable analysis, high IGF2 in the epithelial compartments more than doubled the risk of death in black women; HR = 2.43 (95% CI: 1.18–5.01, P = 0.02) for high IGF2 in the EC; and HR = 2.34 (95% CI: 1.25–4.39, P = 0.008) for high IGF2 in the EN. In conclusion, high tumor IGF2 expression is an independent risk factor for reduced PFS and OS in UCS. Black women have elevated tumor IGF2 compared with white women, and decreased survival associated with high IGF2. These findings identify IGF2 as a candidate biomarker for survival linked to racial disparity in women with UCS.
This study shows that IGF2 protein expression is an independent poor prognostic biomarker in uterine carcinosarcoma, a lethal uterine cancer that disproportionately impacts black women. These novel findings suggest that IGF2 is a biological mediator of an aggressive cancer phenotype and a potential therapeutic target in this disease. Moreover, we have uncovered an intriguing association of IGF2 with racial disparity in uterine carcinosarcoma survival.
http://ift.tt/2o9BgrW
Comparative Study of Different Classification Models in Renal-Cell Carcinoma
Abstract
The aim of this study was to compare the Memorial Sloan-Kettering Cancer Center (MSKCC) and the Cleveland Clinic Foundation (CCF) models of classification of aRCC patients. In addition, the model developed from the pivotal trial of temsirolimus and those proposed by Motzer et al. in 2004, Escudier et al., Heng et al., Choueiri et al. and Bamias et al. were examined. An observational, retrospective study of patients starting first-line systemic therapy was conducted between 2008 and 2011. The variables used to evaluate the classification models were median overall survival (mOS) and median progression-free survival (mPFS). The comparison of different classification models was performed by comparing the area under the ROC (Receiver Operating Characteristic) curve (AUC) for time-dependent variables proposed by Heagerty. Eighty-eight patients were included. When the different models were compared, it was found that although based on the mOS, the Escudier model had better short-term (1-year) prognostic value, followed by the Heng model; in the long term, the models that presented a higher prognosis capacity were the Hudes and CCF models, closely followed by the Heng model. In addition, the Heng model had a slightly higher predictive ability than the other models. Based on the results, and in line with the European society for medical oncology (ESMO) guidelines, it appears that the model of Heng could be the best model to classify patients with aRCC and combines good short- and long-term prognostics while possessing better predictive ability and a more equal distribution of patients.
http://ift.tt/2FbnwEh
Age-Related Hearing Impairment Associated NAT2 , GRM7 , GRHL2 Susceptibility Gene Polymorphisms and Haplotypes in Roma and Hungarian Populations
Abstract
Age-related hearing impairment (ARHI) is the most frequent sensory disease in the elderly, which is caused by an interaction between genetic and environmental factors. Here we examined the ethnic differences, allele and genotype frequencies of the NAT2, GRM7, and GRHL2 genes pooled samples of healthy Hungarian and healthy and hearing impaired Roma people. Study populations of healthy Hungarian and Roma subjects were characterized for the rs1799930 NAT2, rs11928865 GRM7, rs10955255, rs13263539, and rs1981361 GRHL2 polymorphisms and deaf Roma subjects were characterized for the rs1799930 NAT2, rs13263539, and rs1981361 GRHL2 using a PCR-RFLP method. We found significant differences in minor allele frequencies for GRHL2 rs13263539 and rs1981361 polymorphism between healthy Roma and Hungarian samples (37.9% vs. 51.0% and 43.6% vs. 56.2%, respectively; p < 0.05). The differences of homozygous genotype of GRHL2 rs13263539 and rs1981361 variants, values were also significantly different (13.0% vs. 25.3% and 16.5 vs. 32.3%; p < 0.05). The NAT2 rs1799930 homozygous genotype was 14.0% in healthy Romas and 7.7% in Hungarians, while the minor A allele frequency was 38.0% and 26.7% in Roma and Hungarian population, respectively (p < 0.05). Furthermore, the frequency of GGT, GAC and GAT haplotypes was significantly higher in the Hungarian population than in healthy Roma (1.87 vs. 4.47%, 0.91 vs. 2.07% and 1.15 vs. 5.51%, respectively; p < 0.008). Present study revealed significant interethnic differences in allele polymorphisms of NAT2, GRM7 and GRHL2 exhibit quite marked ethnic differences in Roma populations that might have important implications for the preventive and therapeutic treatments in this population.
http://ift.tt/2C3BV6Y
Dual-Stained Cervical Cytology and Histology with Claudin-1 and Ki67
Abstract
Several biomarkers are in use to improve the sensitivity and specificity of cervical cancer screening. Previously, increased expression of tight junction protein claudin-1 (CLDN1) was detected in premalignant and malignant cervical lesions and applied for cytology screening. To improve the specificity, a double immunoreaction with CLDN1/Ki67 was developed in the recent study. Parallel p16/Ki67 (CINtec® PLUS) and CLDN1/Ki67 dual-stained cytology and histology were performed and compared. p16/Ki67 immunoreaction showed positivity in 317 out of 1596 smears with negativity in 1072 and unacceptable reactions in 207 samples. CLDN1/Ki67 dual staining was positive in 200 of 1358 samples, negative in 962, whereas 196 smears could not be evaluated due to technical reasons. Considering the high-grade squamous intraepithelial lesion cytology as gold standard, sensitivity of CLDN1/Ki67 reaction was 76%, specificity was 85.67%, while for p16/Ki67 sensitivity was 74% and specificity was 81.38%. Comparison of CLDN1/Ki67 and p16/Ki67 dual stainings showed the results of the two tests not to be significantly different. Analysing histological slides from 63 cases, the results of the two tests agreed perfectly. As conclusion the sensitivity and specificity proved to be similar using p16/Ki67 and CLDN1/Ki67 double immunoreactions both on LBC samples and on histological slides.
http://ift.tt/2BtmpQP
Miki (Mitotic Kinetics Regulator) Immunoexpression in Normal Liver, Cirrhotic Areas and Hepatocellular Carcinomas: a Preliminary Study with Clinical Relevance
Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary malignant tumor in the liver. One of the main features of cancer survival is the generalized loss of growth control exhibited by cancer cells, and Miki is a protein related to the immunoglobulin superfamily that plays an important role in mitosis. We aim to study protein expression levels of Miki in non-tumoral liver and 20 HCCs recruited from a Pathology Department. Clinical information was also obtained. A tissue microarray was performed, and immunohistochemical techniques applied to study protein expression levels of Miki. In normal liver, Miki was weakly expressed, showing nuclear staining in the hepatocytes. Cirrhotic areas and HCCs showed a variety of staining patterns. Most HCC samples showed positive expression, with three different staining patterns being discernible: nuclear, cytoplasmic and mixed. Statistical analysis showed a significant association between grade of differentiation, Ki-67 proliferative index, survival rates and staining patterns. This study has revealed the positive expression of Miki in normal liver, cirrhotic areas and HCCs. Three different staining patterns of Miki expression with clinical relevance were noted in HCCs.
http://ift.tt/2EZveBi
Comparative Study of Different Classification Models in Renal-Cell Carcinoma
Abstract
The aim of this study was to compare the Memorial Sloan-Kettering Cancer Center (MSKCC) and the Cleveland Clinic Foundation (CCF) models of classification of aRCC patients. In addition, the model developed from the pivotal trial of temsirolimus and those proposed by Motzer et al. in 2004, Escudier et al., Heng et al., Choueiri et al. and Bamias et al. were examined. An observational, retrospective study of patients starting first-line systemic therapy was conducted between 2008 and 2011. The variables used to evaluate the classification models were median overall survival (mOS) and median progression-free survival (mPFS). The comparison of different classification models was performed by comparing the area under the ROC (Receiver Operating Characteristic) curve (AUC) for time-dependent variables proposed by Heagerty. Eighty-eight patients were included. When the different models were compared, it was found that although based on the mOS, the Escudier model had better short-term (1-year) prognostic value, followed by the Heng model; in the long term, the models that presented a higher prognosis capacity were the Hudes and CCF models, closely followed by the Heng model. In addition, the Heng model had a slightly higher predictive ability than the other models. Based on the results, and in line with the European society for medical oncology (ESMO) guidelines, it appears that the model of Heng could be the best model to classify patients with aRCC and combines good short- and long-term prognostics while possessing better predictive ability and a more equal distribution of patients.
http://ift.tt/2FbnwEh
ESMO 2017—my personal highlights
Summary
This article is not intended to be a comprehensive review of all highlights presented at the recent ESMO Annual Meeting, but rather a summary from a personal point of view in three very different fields of oncology. Breast cancer and lung cancer are traditionally in the focus of interest, and again, relevant new data were presented. The third part of this overview is focused on novel treatment strategies in malignant lymphoma, a field that is also quickly evolving and traditionally underrepresented at meetings dealing with solid cancers.
http://ift.tt/2C8Q030
Anti-angiogenic therapies in brain metastases
Summary
Brain metastases are a major challenge in modern oncology, as treatment options upon the diagnosis of symptomatic brain metastases are limited. Neo-angiogenesis was identified as a hallmark of brain metastasis development and inhibition using anti-angiogenic therapy might therefore be an experimental promising preventive as well as therapeutic approach. The current review will summarize the current available data on the efficacy of neo-angiogenic therapies in patients with brain metastases.
http://ift.tt/2BAutit
ESMO 2017—my personal highlights
Summary
This article is not intended to be a comprehensive review of all highlights presented at the recent ESMO Annual Meeting, but rather a summary from a personal point of view in three very different fields of oncology. Breast cancer and lung cancer are traditionally in the focus of interest, and again, relevant new data were presented. The third part of this overview is focused on novel treatment strategies in malignant lymphoma, a field that is also quickly evolving and traditionally underrepresented at meetings dealing with solid cancers.
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Anti-angiogenic therapies in brain metastases
Summary
Brain metastases are a major challenge in modern oncology, as treatment options upon the diagnosis of symptomatic brain metastases are limited. Neo-angiogenesis was identified as a hallmark of brain metastasis development and inhibition using anti-angiogenic therapy might therefore be an experimental promising preventive as well as therapeutic approach. The current review will summarize the current available data on the efficacy of neo-angiogenic therapies in patients with brain metastases.
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The Infection Returns: A Case of Pulmonary Sporotrichosis Relapse after Chemotherapy
Background. Pulmonary sporotrichosis is a rare disease caused by a dimorphic fungus, Sporothrix schenckii. It is rarely found in association with malignancy. We present a case of pulmonary sporotrichosis recurrence after chemotherapy. Case Presentation. A 44-year-old man, treated for pulmonary sporotrichosis in the past, presented with dysphagia and was found to have squamous cell carcinoma of the esophagus. After undergoing chemotherapy, extensive cavitary lesions were observed on thoracic computed tomography scan. A bronchoalveolar lavage revealed the presence of Sporothrix schenckii sensu lato. Despite treatment with itraconazole, he eventually required a left pneumonectomy for progressive destructive cavitary lesions involving the left lung. Conclusion. This case highlights the importance of considering past fungal infections, albeit cured, in patients initiating immunosuppressive therapy.
http://ift.tt/2EQqAIu
Carbon-ion radiotherapy for locoregional recurrence after primary surgery for pancreatic cancer
The efficacy and safety of carbon ion radiotherapy (C-ion RT) for locoregional recurrence after surgery for pancreatic cancer were retrospectively evaluated. The results for 30 patients showed that C-ion RT was performed safely with relatively long overall survival, good local control, and minimal toxicity.
http://ift.tt/2C5wapp
Erratum
Publication date: Available online 17 February 2018
Source:Practical Radiation Oncology
http://ift.tt/2ExKYPf
Age-Related Hearing Impairment Associated NAT2 , GRM7 , GRHL2 Susceptibility Gene Polymorphisms and Haplotypes in Roma and Hungarian Populations
Abstract
Age-related hearing impairment (ARHI) is the most frequent sensory disease in the elderly, which is caused by an interaction between genetic and environmental factors. Here we examined the ethnic differences, allele and genotype frequencies of the NAT2, GRM7, and GRHL2 genes pooled samples of healthy Hungarian and healthy and hearing impaired Roma people. Study populations of healthy Hungarian and Roma subjects were characterized for the rs1799930 NAT2, rs11928865 GRM7, rs10955255, rs13263539, and rs1981361 GRHL2 polymorphisms and deaf Roma subjects were characterized for the rs1799930 NAT2, rs13263539, and rs1981361 GRHL2 using a PCR-RFLP method. We found significant differences in minor allele frequencies for GRHL2 rs13263539 and rs1981361 polymorphism between healthy Roma and Hungarian samples (37.9% vs. 51.0% and 43.6% vs. 56.2%, respectively; p < 0.05). The differences of homozygous genotype of GRHL2 rs13263539 and rs1981361 variants, values were also significantly different (13.0% vs. 25.3% and 16.5 vs. 32.3%; p < 0.05). The NAT2 rs1799930 homozygous genotype was 14.0% in healthy Romas and 7.7% in Hungarians, while the minor A allele frequency was 38.0% and 26.7% in Roma and Hungarian population, respectively (p < 0.05). Furthermore, the frequency of GGT, GAC and GAT haplotypes was significantly higher in the Hungarian population than in healthy Roma (1.87 vs. 4.47%, 0.91 vs. 2.07% and 1.15 vs. 5.51%, respectively; p < 0.008). Present study revealed significant interethnic differences in allele polymorphisms of NAT2, GRM7 and GRHL2 exhibit quite marked ethnic differences in Roma populations that might have important implications for the preventive and therapeutic treatments in this population.
http://ift.tt/2C3BV6Y
Editorial Board
Publication date: February 2018
Source:Critical Reviews in Oncology/Hematology, Volume 122
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Editorial Board
Publication date: February 2018
Source:Critical Reviews in Oncology/Hematology, Volume 122
http://ift.tt/2Gp97E9
The anti-malarial mefloquine inhibits NF-κB signaling and induces apoptosis in colorectal cancer cells
Abstract
The NF-κB signaling pathway is activated in many colorectal cancer (CRC) cells and in the tumor microenvironment, which plays a critical role in cancer initiation, development, and response to therapies. We found in the present study that the widely used antimalarial drug mefloquine was a NF-κB inhibitor that blocked the activation of IκBα kinase, leading to the reduction of IκBα degradation, decrease of p65 phosphorylation, and suppressed expression of NF-κB target genes in colorectal cancer cells. We also found that mefloquine induced growth arrest and apoptosis of colorectal cancer cells harboring phosphorylated p65 in culture and mice. Furthermore, expression of constitutive active IKKβ kinase significantly attenuated the cytotoxic effect of the compound. These results demonstrated that mefloquine could exert anti-tumor action through inhibiting the NF-κB signaling pathway, and indicated that the antimalaria drug might be re-purposed for anti-CRC therapy in clinic as a single agent or in combination with other anti-cancer drugs.
This article is protected by copyright. All rights reserved.
http://ift.tt/2sAL4Ql
Downregulation of reticulocalbin-1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells
Abstract
Reticulocalbin 1 (RCN1), an endoplasmic reticulum (ER)-resident Ca2+-binding protein, is dysregulated in cancers, but its pathophysiological roles are largely unclear. Here, we demonstrate that RCN1 is overexpressed in clinical prostate cancer (PCa) samples, associated with Cyclin B, not Cyclin D1 expression, compared to that of benign tissues in a Chinese Han population. Downregulation of endogenous RCN1 significantly suppresses PCa cell viability and arrests the cell cycles of DU145 and LNCaP cells at the S and G2/M phases, respectively. RCN1 depletion causes ER stress, which is evidenced by induction of GRP78, activation of PERK, and phosphorylation of eIF2α in PCa cells. Remarkably, RCN1 loss triggers DU145 cell apoptosis in a caspase-dependent manner but mainly causes necroptosis in LNCaP cells. An animal based analysis confirms that RCN1 depletion suppresses cell proliferation and promotes cell death. Further investigations reveal that RCN1 depletion leads to elevation of PTEN and inactivation of AKT in DU145 cells. Silencing of PTEN partially restores apoptotic cells upon RCN1 loss. In LNCaP cells, predominant activation of CaMKII is important for necroptosis in response to RCN1 depletion. Thus, RCN1 may promote cell survival and serve as a useful target for cancer therapy.
This article is protected by copyright. All rights reserved.
http://ift.tt/2C4a5Yd
The anti-malarial mefloquine inhibits NF-κB signaling and induces apoptosis in colorectal cancer cells
Abstract
The NF-κB signaling pathway is activated in many colorectal cancer (CRC) cells and in the tumor microenvironment, which plays a critical role in cancer initiation, development, and response to therapies. We found in the present study that the widely used antimalarial drug mefloquine was a NF-κB inhibitor that blocked the activation of IκBα kinase, leading to the reduction of IκBα degradation, decrease of p65 phosphorylation, and suppressed expression of NF-κB target genes in colorectal cancer cells. We also found that mefloquine induced growth arrest and apoptosis of colorectal cancer cells harboring phosphorylated p65 in culture and mice. Furthermore, expression of constitutive active IKKβ kinase significantly attenuated the cytotoxic effect of the compound. These results demonstrated that mefloquine could exert anti-tumor action through inhibiting the NF-κB signaling pathway, and indicated that the antimalaria drug might be re-purposed for anti-CRC therapy in clinic as a single agent or in combination with other anti-cancer drugs.
This article is protected by copyright. All rights reserved.
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Downregulation of reticulocalbin-1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells
Abstract
Reticulocalbin 1 (RCN1), an endoplasmic reticulum (ER)-resident Ca2+-binding protein, is dysregulated in cancers, but its pathophysiological roles are largely unclear. Here, we demonstrate that RCN1 is overexpressed in clinical prostate cancer (PCa) samples, associated with Cyclin B, not Cyclin D1 expression, compared to that of benign tissues in a Chinese Han population. Downregulation of endogenous RCN1 significantly suppresses PCa cell viability and arrests the cell cycles of DU145 and LNCaP cells at the S and G2/M phases, respectively. RCN1 depletion causes ER stress, which is evidenced by induction of GRP78, activation of PERK, and phosphorylation of eIF2α in PCa cells. Remarkably, RCN1 loss triggers DU145 cell apoptosis in a caspase-dependent manner but mainly causes necroptosis in LNCaP cells. An animal based analysis confirms that RCN1 depletion suppresses cell proliferation and promotes cell death. Further investigations reveal that RCN1 depletion leads to elevation of PTEN and inactivation of AKT in DU145 cells. Silencing of PTEN partially restores apoptotic cells upon RCN1 loss. In LNCaP cells, predominant activation of CaMKII is important for necroptosis in response to RCN1 depletion. Thus, RCN1 may promote cell survival and serve as a useful target for cancer therapy.
This article is protected by copyright. All rights reserved.
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Erratum
http://ift.tt/2odu1yF
Alachlor Use and Cancer Incidence in the Agricultural Health Study: An Updated Analysis
http://ift.tt/2o6igul
Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) for Prevention of Breast Cancer-Related Lymphedema—a Preliminary Report
Abstract
Lymphatic microsurgical preventing healing approach (LYMPHA) for prevention of breast cancer-related lymphedema (BCRL)—a preliminary report BCRL—is a chronic debilitating condition which impairs quality of life of breast cancer survivors. The aim is to study the feasibility of preventing lymphedema by performing "Lymphatic Microsurgical Preventive Healing Approach (LYMPHA)." Patients undergoing breast cancer surgery with complete nodal dissection were taken up for the study. After the standard axillary nodal dissection, lymphatics were identified by the help of blue dye and were anastomosed with a tributary to the axillary vein. Post-operatively, patients were followed up clinically for development of lymphedema and lymphoscintigraphy was performed after treatment completion. A total of 35 patients were enrolled for the study. The average BMI was 29.5. LYMPHA was feasible in all cases. The number of lymphatics identified was 1 to 5 per axilla. Two patients developed transient lymphedema which resolved with conservative therapy and patients were able to discontinue the compression garment. Follow-up lymphoscintigraphy is performed in two patients, which showed normal lymphatic flow. LYMPHA is a feasible technique, not difficult to perform, takes a short time, is accomplished in same general anesthesia as for axillary dissection, and gives no extra scar. The early results are promising and long-term follow-up may make the procedure as a routine.
http://ift.tt/2GjGM1K
Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) for Prevention of Breast Cancer-Related Lymphedema—a Preliminary Report
Abstract
Lymphatic microsurgical preventing healing approach (LYMPHA) for prevention of breast cancer-related lymphedema (BCRL)—a preliminary report BCRL—is a chronic debilitating condition which impairs quality of life of breast cancer survivors. The aim is to study the feasibility of preventing lymphedema by performing "Lymphatic Microsurgical Preventive Healing Approach (LYMPHA)." Patients undergoing breast cancer surgery with complete nodal dissection were taken up for the study. After the standard axillary nodal dissection, lymphatics were identified by the help of blue dye and were anastomosed with a tributary to the axillary vein. Post-operatively, patients were followed up clinically for development of lymphedema and lymphoscintigraphy was performed after treatment completion. A total of 35 patients were enrolled for the study. The average BMI was 29.5. LYMPHA was feasible in all cases. The number of lymphatics identified was 1 to 5 per axilla. Two patients developed transient lymphedema which resolved with conservative therapy and patients were able to discontinue the compression garment. Follow-up lymphoscintigraphy is performed in two patients, which showed normal lymphatic flow. LYMPHA is a feasible technique, not difficult to perform, takes a short time, is accomplished in same general anesthesia as for axillary dissection, and gives no extra scar. The early results are promising and long-term follow-up may make the procedure as a routine.
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Cancers, Vol. 10, Pages 54: Advanced EUS Guided Tissue Acquisition Methods for Pancreatic Cancer
Cancers, Vol. 10, Pages 54: Advanced EUS Guided Tissue Acquisition Methods for Pancreatic Cancer
Cancers doi: 10.3390/cancers10020054
Authors: Pujan Kandel Michael B. Wallace
Pancreas cancer is a lethal cancer as the majority patients are diagnosed at an advanced incurable stage. Despite improvements in diagnostic modalities and management strategies, including surgery and chemotherapies, the outcome of pancreas cancer remains poor. Endoscopic ultrasound (EUS) is an important imaging tool for pancreas cancer. For decades, resected pancreas cancer and other cancer specimens have been used to identify tissue biomarkers or genomics for precision therapy; however, only 20% of patients undergo surgery, and thus, this framework is not useful for unresectable pancreas cancer. With advancements in needle technologies, tumor specimens can be obtained at the time of tissue diagnosis. Tumor tissue can be used for development of personalized cancer treatment, such as performing whole exome sequencing and global genomic profiling of pancreas cancer, development of tissue biomarkers, and targeted mutational assays for precise chemotherapy treatment. In this review, we discuss the recent advances in tissue acquisition of pancreas cancer.
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Cancers, Vol. 10, Pages 54: Advanced EUS Guided Tissue Acquisition Methods for Pancreatic Cancer
Cancers, Vol. 10, Pages 54: Advanced EUS Guided Tissue Acquisition Methods for Pancreatic Cancer
Cancers doi: 10.3390/cancers10020054
Authors: Pujan Kandel Michael B. Wallace
Pancreas cancer is a lethal cancer as the majority patients are diagnosed at an advanced incurable stage. Despite improvements in diagnostic modalities and management strategies, including surgery and chemotherapies, the outcome of pancreas cancer remains poor. Endoscopic ultrasound (EUS) is an important imaging tool for pancreas cancer. For decades, resected pancreas cancer and other cancer specimens have been used to identify tissue biomarkers or genomics for precision therapy; however, only 20% of patients undergo surgery, and thus, this framework is not useful for unresectable pancreas cancer. With advancements in needle technologies, tumor specimens can be obtained at the time of tissue diagnosis. Tumor tissue can be used for development of personalized cancer treatment, such as performing whole exome sequencing and global genomic profiling of pancreas cancer, development of tissue biomarkers, and targeted mutational assays for precise chemotherapy treatment. In this review, we discuss the recent advances in tissue acquisition of pancreas cancer.
http://ift.tt/2GoWIjh
Takotsubo syndrome in a premenopausal patient
Takotsubo syndrome is a rare clinical condition, with a pathophysiology that is not fully understood. Characterised by an acute and usually reversible heart failure, the condition is often preceded by a stressful event. For the diagnosis of Takotsubo syndrome to be possible, the absence of coronary artery disease as a cause is required. We report a case of Takotsubo syndrome in a 47-year-old woman of fertile age. Electrical and echocardiographic presentations were classical in the patient. However, abnormally elevated cardiac biomarkers were registered. The patient showed signs of clinical improvement, with a follow-up angiography excluding coronary artery disease and therefore leading to a diagnosis of Takotsubo syndrome.
http://ift.tt/2EyjngW
Bladder necrosis: 'A man without a bladder
Since the use of antibiotics, bladder necrosis has become a rare condition. We report a case of bladder necrosis in a 90-year-old man following urinary retention. After insertion of a transurethral catheter (TUC), 2 L of urine was evacuated. In the following days, the TUC became intermittently blocked. Adequate bladder drainage could not be obtained despite intensive rinsing and placement of a suprapubic catheter. On surgical exploration necrosis of almost the entire bladder wall, except for the trigone, was encountered. Surgical debridement of the non-viable bladder wall without opening the abdominal cavity was conducted, and a TUC was placed in the Retzius cavity to ensure evacuation of urine. Since the patient was haemodynamically unstable, construction of a urinary diversion was waived and urinary drainage of the Retzius cavity by the TUC was accepted, resulting in adequate urinary drainage without compromising renal function.
http://ift.tt/2BzEFb4
Disabling pansclerotic morphoea of childhood
Disabling pansclerotic morphoea (DPM) of childhood is a severe and often fatal variant of deep morphoea. It usually starts in childhood and rarely seen in adults. The course of the disease is progressive with lifelong morbidity in the form of joint contractures and immobility. The causes of mortality include complications such as sepsis, gangrene and cardiopulmonary involvement. Herein, we discuss the case of a 15-year-old girl with limb deformity and finger contractures, that is, bone involvement. The diagnosis of DPM of childhood was fortuitously made after the correction of limb deformity, when the patient was seen in the dermatology department for evaluation of skin discolouration on the thighs.
http://ift.tt/2EyjiKa
When a polyp is not a polyp: incidental finding of a sigmoid schwannoma at first colonoscopic screening
Schwannomas, peripheral nerve sheath tumours arising from Schwann cells, are often associated with inherited disorders such as neurofibromatosis. Gastrointestinal schwannomas, while rare, have been reported in those without personal or family history of neurofibromatosis. Diagnoses of these lesions, however, typically follow evaluations prompted by symptomatic presentations associated with abdominal pain, rectal bleeding, change in bowel habits or positive results on faecal occult blood tests performed for colorectal cancer screening. Further, management of these predominantly benign lesions commonly incorporates surgical resection. We present the case of a sigmoid schwannoma found in an asymptomatic individual on first screening colonoscopy and treated with complete endoscopic polypectomy with anticipated surveillance colonoscopy.
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Pulmonary inflammatory myofibroblastic tumour misdiagnosed as a round pneumonia
Description
A 9-year-old male patient, previously healthy, presented with acute-onset chest pain. The pain was on the right lateral chest, 10/10 in severity and non-reproducible. The patient had 1-week history of cough that had been improving; no fever, weight loss, dyspnoea, palpitations or night sweats were reported. He had positive sick contacts. Examination was remarkable for slight decrease in breath sounds at the right lower lung field posteriorly. Initial chest radiograph showed a well-circumscribed opacity in the right lower lobe posteriorly with adjacent consolidation seen on the lateral view. The lesion appeared to be distinct from the cardiomediastinal silhouette (figure 1). Sonography was performed to characterise the nature of the lesion; however, it was difficult to visualise and only revealed mixed echotexture (figure 2). Contrast-enhanced CT scan of the thorax was then obtained. CT showed a right posterior basal segment consolidation with hypo-enhancing components...
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Late diagnosis: a case of rapidly progressive extranodal NK/T cell lymphoma, nasal type
Extranodal natural killer (NK)/T cell lymphoma, nasal type is a condition that has poor prognosis. Accurate diagnosis of lymphoma is made by pathological findings. We report a case of extranodal NK/T cell lymphoma, nasal type affecting the lung and liver and which was difficult to diagnose because of negative biopsy results from multiple sites. A 39-year-old man who had dry cough and fever for 1 month was referred to our hospital. He had pancytopenia and elevated serum levels of lactate dehydrogenase and soluble interleukin-2 receptor. Hepatosplenomegaly and multiple lung nodules were found on imaging study. Specimens of bronchoscopic lung, percutaneous liver, bone marrow and random skin biopsies were all negative. Open lung biopsy was not definitive. Unfortunately, disease progression was rapid and fatal before results of pleural fluid cytology and a second liver biopsy showed extranodal NK/T cell lymphoma, nasal type. This report focused on diagnostic planning for rapidly progressive extranodal NK/T-cell lymphoma, nasal type.
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A quintessential syndrome with a rare marvelling aetiology: Rosai-Dorfman disease presenting as Conus-Cauda syndrome
A 19-year-old woman presented with a history of severe lower backache and asymmetric proximal lower limb weakness during the past 3 months. In addition, she also suffered from lower motor neuron-type bladder and bowel symptoms. On examination, paraparesis was noted. Further, sensory examination suggested patchy asymmetric sensory loss in both lower limbs with saddle anaesthesia and areflexia. A clinical diagnosis of Conus-Cauda syndrome was made and contrast-enhanced MRI of the lumbar and sacral spine was done, which confirmed the presence of a mass lesion within the spinal canal involving the cauda equina extending up to the sacral level. She underwent partial resection of the lesion following which the neurological deficits and lower backache resolved. Histopathological evaluation and immunohistochemical analyses uncovered Rosai-Dorfman disease. There was no evidence of disease elsewhere in the body. Since the patient improved significantly following surgery and exhibited no further neurological worsening, she remains under close follow-up.
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NMDAR (N-methyl-D-aspartate receptor) encephalitis in a patient with MS (multiple sclerosis): a rare and challenging case
We present a rare case of N-methyl-D-aspartate receptor (NMDAR) encephalitis in a 41-year-old Caucasian woman, who initially presented with prominent neuropsychiatric symptoms on the background of pre-existing multiple sclerosis. Here, the authors navigate the muddy water between neurology and psychiatry, describing the caveats of antibody testing with a misdiagnosed case of acute and transient psychotic episode. NMDAR encephalitis in MS is a rare condition, which can be easily confused with a new onset psychotic episode. This case report can be helpful in recognition and diagnosis of this rare condition. Making the right diagnosis is important since it can prevent an unnecessary radical treatment and long-term neuropsychiatric complications.
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2017 Thank you to our reviewers
The Editor would like to publicly acknowledge the people listed below who served as reviewers on the journal during 2017. Without their efforts, the quality of the journal could not be sustained.
A-Cienfuegos, Javier
A.C, Jyothi
Aaronson, Nicole
Abba-Aji, Adam
Abbas, Ossama
Abbas, Syed Hussain
Abbey-Mensah, Geraldine
Abbott, Iain
Abd El-Latif, Amani N
Abdalla, Ahmed
Abdallah, Hassane
Abdel Hay, Sameh
Abdel Razek, Ahmed
Abdeldayem, Hussein
Abdelgadir, Ibtihal
Abdul Haium, Abdul Alim
Abduljabbar, Fahad
Abdullah, Ibrahim
Abdullah, Nurul
Abdussalam, Abdullah
Abe, Kazuo
Abe, Tomomi
Abegunde, Ayokunle
Abeygunasekara, Anuruddha
Abid, Noina
Abou Dargham, Hanadi
Abourazzak, Sana
Abreo, Kenneth
Abreo, Mohini
Abu Amna, Fatima
Abu Bakar, Mohd Zulkiflee
Abu Freha, Naim
Abu Saadeh, Feras
Abu-Arafeh, I
Abu-Zaid, Ahmed
Abuomara, Hossamaldin
Acar, Fahrettin
Aceto, P
Acheampong, Derrick
Acien, Pedro
Adachi, Masanori
Adam, D.N
Adam, Ervin
Adam, Ishag
Adams, Daniel
Adams, Derick
Adams, G. G. W
Adams, Nicholas
Adams, Phil
Adamski, Jill
Adebajo, Ade
...http://ift.tt/2EAGB63
A child with tubulointerstitial nephritis and uveitis (TINU) syndrome
Tubulointerstitial nephritis and uveitis syndrome is an uncommon disease, probably underdiagnosed in clinical practice. Its aetiology and pathogenesis remain unknown. This syndrome is defined by an association of uveitis and tubulointerstitial nephritis, with no evidence of systemic disease or infection that might cause both ocular and renal inflammation. Renal and ocular manifestations may not occur simultaneously, making the diagnosis even more challenging. Treatment includes topical and oral corticosteroids. Renal involvement usually resolves spontaneously with full recovery of kidney function, however uveitis can persist or recur years after its initial presentation. We report a case of a 13-year-old girl with tubulointerstitial nephritis and uveitis syndrome.
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PD1 protein expression in tumor infiltrated lymphocytes rather than PDL1 in tumor cells predicts survival in triple-negative breast cancer
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Body mass index in HER2-negative metastatic breast cancer treated with first-line paclitaxel and bevacizumab
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Expression analysis of liver-specific circulating microRNAs in HCV-induced hepatocellular Carcinoma in Egyptian patients
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Prostate-specific membrane antigen in breast cancer: a comprehensive evaluation of expression and a case report of radionuclide therapy
Abstract
Purpose
Prostate-specific membrane antigen (PSMA), a protein product of the folate hydrolase 1 (FOLH1) gene, is gaining increasing acceptance as a target for positron emission tomography/computer tomography (PET/CT) imaging in patients with several cancer types, including breast cancer. So far, PSMA expression in breast cancer endothelia has not been sufficiently characterized.
Methods
This study comprised 315 cases of invasive carcinoma of no special type (NST) and lobular breast cancer (median follow-up time 9.0 years). PSMA expression on tumor endothelia was detected by immunohistochemistry. Further, vascular mRNA expression of the FOLH1 gene (PSMA) was investigated in a cohort of patients with invasive breast cancer provided by The Cancer Genome Atlas (TCGA).
Results
Sixty percent of breast cancer cases exhibited PSMA-positive endothelia with higher expression rates in tumors of higher grade, NST subtype with Her2-positivity, and lack of hormone receptors. These findings were confirmed on mRNA expression levels. The highest PSMA rates were observed in triple-negative carcinomas (4.5 × higher than in other tumors). Further, a case of a patient with metastatic breast cancer showing PSMA expression in PET/CT imaging and undergoing PSMA radionuclide therapy is discussed in detail.
Conclusions
This study provides a rationale for the further development of PSMA-targeted imaging in breast cancer, especially in triple-negative tumors.
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Extraordinary disease-free survival in a rare malignant extrarenal rhabdoid tumor: a case report and review of the literature
Malignant extrarenal rhabdoid tumor of the gastrointestinal tract is rarely reported in the literature. It is characterized by poor prognosis and aggressive metastatic features.
http://ift.tt/2CrfkNp
HPV genotyping for the cross-sectional and longitudinal probability of developing CIN2+
Abstract
HPV testing is more sensitive but less specific than cytology. We evaluated stand-alone genotyping as a possible triage method.
During a multicentre randomised controlled trial comparing HPV testing to conventional cytology, HPV positive women were referred to colposcopy and followed up if no high-grade lesion was detected. HPV positive samples were genotyped by GP5+/GP6+ primed PCR followed by reverse line blot. Genotypes were hierarchically ordered by positive predictive value (PPV) for CIN grade 2 or more (CIN2+), and grouped by cluster analysis into 3 groups (A, B and C in decreasing order). Receiver Operating Characteristic (ROC) curves were computed.
Among 2255 HPV positive women with genotyping, 239 CIN2+ (including 113 CIN3+) were detected at baseline or during a 3-year follow-up. HPV33 had the highest PPV with CIN2+ and CIN3+ as the endpoint and when considering lesions detected at baseline or also during follow-up. HPV16 and HPV35 were the second and third, respectively. Cross-sectional sensitivity for CIN2+ at baseline was 67.3% (95% CI 59.7-74.2), 91.8% (95% CI 86.6-95.5) and 94.7% (95% CI 90.2-97.6) respectively when considering as "positive" any of the HPV types in group A (33, 16, 35), A or B (31, 52, 18, 59, 58) and A or B or C (39, 51, 56, 45, 68). The corresponding cross sectional PPVs for CIN2+ were 15.8% 95% CI 13.2-18.7), 12.0% (95% CI 10.3-13.9) and 9.6% (95% CI 8.2-11.1), respectively.
HPV33, 16 and 35 confer a high probability of CIN2+ but this rapidly decreases when adding other genotypes. This article is protected by copyright. All rights reserved.
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Patient-reported predictors of early treatment discontinuation: treatment-related symptoms and health-related quality of life among postmenopausal women with primary breast cancer randomized to anastrozole or exemestane on NCIC Clinical Trials Group (CCTG) MA.27 (E1Z03)
Abstract
Purpose
Aromatase inhibitors are the most commonly prescribed adjuvant endocrine therapy for hormone-dependent early breast cancer in postmenopausal women. Among Canadian Cancer Trials Group MA.27 participants, anastrozole and exemestane had comparable 5-year event-free survival. This companion study examined differences in patient-reported treatment-related symptoms (TRS) and health-related quality of life (HRQL) among postmenopausal women randomized to anastrozole or exemestane.
Methods
MA.27 participants (N = 686, of 7576) randomized to 5 years of anastrozole (1 mg/day, n = 371, Arm A) or exemestane (25 mg/day, n = 315, Arm E) completed the 56-item Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES) questionnaire to assess TRS and HRQL. The FACT-ES was completed at baseline, 3, 6, 12, and 24 months.
Results
No significant differences in FACT-ES median scores measuring TRS and HRQL were observed between treatment arms at any time point. Change in TRS from baseline was statistically significant at 3, 6, 12, and 24 months. HRQL was stable over time in both arms. Greater TRS burden was associated with poorer HRQL (coefficient = 0.57, p < 0.001). Twenty percent of patients discontinued AI therapy by month 24 and 32% discontinued AIs at 4 years. In both arms, patients reporting more side effect bother prior to initiating study treatment had a higher risk of discontinuing treatment before completing protocol therapy (hazard ratio [HR] 1.29, 95% CI 1.08–1.55, p = 0.01).
Conclusions
TRS and HRQL were comparable between anastrozole and exemestane. TRS negatively affect HRQL. Women who report being bothered by treatment side effects prior to initiating an AI are at increased risk for early treatment discontinuation.
http://ift.tt/2o7wrzv
HPV genotyping for the cross-sectional and longitudinal probability of developing CIN2+
Abstract
HPV testing is more sensitive but less specific than cytology. We evaluated stand-alone genotyping as a possible triage method.
During a multicentre randomised controlled trial comparing HPV testing to conventional cytology, HPV positive women were referred to colposcopy and followed up if no high-grade lesion was detected. HPV positive samples were genotyped by GP5+/GP6+ primed PCR followed by reverse line blot. Genotypes were hierarchically ordered by positive predictive value (PPV) for CIN grade 2 or more (CIN2+), and grouped by cluster analysis into 3 groups (A, B and C in decreasing order). Receiver Operating Characteristic (ROC) curves were computed.
Among 2255 HPV positive women with genotyping, 239 CIN2+ (including 113 CIN3+) were detected at baseline or during a 3-year follow-up. HPV33 had the highest PPV with CIN2+ and CIN3+ as the endpoint and when considering lesions detected at baseline or also during follow-up. HPV16 and HPV35 were the second and third, respectively. Cross-sectional sensitivity for CIN2+ at baseline was 67.3% (95% CI 59.7-74.2), 91.8% (95% CI 86.6-95.5) and 94.7% (95% CI 90.2-97.6) respectively when considering as "positive" any of the HPV types in group A (33, 16, 35), A or B (31, 52, 18, 59, 58) and A or B or C (39, 51, 56, 45, 68). The corresponding cross sectional PPVs for CIN2+ were 15.8% 95% CI 13.2-18.7), 12.0% (95% CI 10.3-13.9) and 9.6% (95% CI 8.2-11.1), respectively.
HPV33, 16 and 35 confer a high probability of CIN2+ but this rapidly decreases when adding other genotypes. This article is protected by copyright. All rights reserved.
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