Pancreatic cancer adjuvant radiotherapy target volume design: based on the postoperative local recurrence spatial location

Abstract

Objectives

To explore the areas at highest risk for postoperative pancreatic cancer local recurrence according to the spatial location of local failures, with the aim to provide a precise target volume for pancreatic cancer adjuvant radiotherapy.

Methods

Patients with pancreatic cancer who had undergone surgery for the primary tumor in pancreas at our institution from January 2010 to August 2015 were retrospectively analyzed. All local recurrences were plotted on the computed tomography (CT) image of a representative patient according to their relative coordinates to superior mesenteric artery (SMA) or celiac axis (CA). Adjuvant radiation clinical target volume (CTV)-90 and CTV-80 were created to cover 90 % and 80 % plotted recurrences. This planning approach was applied in four simulated cases with comparison to the plan according to RTOG 0848 contouring consensus guidelines. Raystation v4.5.1.14 was used for analyzing high throughput physics data.

Results

Eighty-three patients with local recurrence were included from 305 postoperative pancreatic cancer patients who did not receive adjuvant radiotherapy. Thirty-one (37 %) patients did not have adjuvant therapy at all, 52 (63 %) patients undergone adjuvant chemotherapy alone. Spatial location of local failure was created. Most recurrences occurred near CA or SMA. CTV-90 was generated through expanding the combined SMA and CA contours by 30 mm right-lateral, 21 mm left-lateral, 20 mm anterior, 13 mm posterior, 10 mm superior, and 20 mm inferior. CTV-80, smaller in volume, was also created for simultaneous integrated boost. Through comparison and analysis of the simulated cases, the radiation volumes proposed were much smaller than those with RTOG 0848 contouring consensus guidelines (average volume: PTV-80 = 120 ml, PTV-90 = 220 ml, RTOG PTV = 490 ml). Accordingly, the organs at risk received less irradiation dose with the proposed CTV-90 and CTV-80.

Conclusions

Smaller adjuvant radiotherapy CTVs targeting the high-risk local failure areas of postoperative pancreatic cancer were proposed, according to the three-dimensional spatial location of local recurrences. This may help to minimize radiation-related toxicities, achieve dose escalation, and finally reduce local recurrence.

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Effectiveness of postoperative elemental diet (Elental®) in elderly patients after gastrectomy

Abstract

Background

We aimed to investigate the efficacy of postoperative early intervention with an elemental diet to reduce weight loss and enhance recovery after gastrectomy. Nutritional status and gastrointestinal immune function tend to worsen, and postoperative weight loss is inevitable in these patients; therefore, improvement in their postoperative condition is important, especially in gastric cancer patients aged ≥80 years.

Methods

Clinical outcomes and postoperative nutritional status were compared between 21 and 22 consecutive elderly patients aged ≥80 years who underwent distal gastrectomy before and after the introduction of postoperative oral elemental diet (Elental®, 300 kcal/day), respectively, between October 2011 and June 2016.

Results

A significant reduction in postoperative complications was noted in the nutrition support group (N-group) as compared with the control group (C-group). In particular, the prevalence of systemic complications was significantly lower in the N-group (33.3 vs. 4.5 %, p = 0.015), whereas no significant difference was observed in the prevalence of locoregional complications. The percentage of weight loss and reduction in BMI from 1 month to 1 year after surgery was significantly lower in the N-group (p = 0.012 each). The nutrition status (albumin, total protein, hemoglobin, and C-reactive protein levels) at 1 month after surgery showed improvements (p = 0.005, p = 0.048), and hospital stay was decreased in the N-group as compared to the C-group (16.0 vs. 12.5 days, p = 0.041).

Conclusions

Early intervention with an elemental diet after distal gastrectomy is valuable for reducing perioperative weight loss and improving nutritional management and may be associated with enhanced postoperative recovery in elderly patients.

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Depletion of thymopoietin inhibits proliferation and induces cell cycle arrest/apoptosis in glioblastoma cells

Abstract

Background

Glioblastoma (GBM) is the most malignant nervous system tumor with an almost 100 % recurrence rate. Thymopoietin (TMPO) has been demonstrated to be upregulated in various tumors, including lung cancer, breast cancer, and so on, but its role in GBM has not been reported. This study was aimed to determine the role of TMPO in GBM.

Methods

Publicly available Oncomine dataset analysis was used to explore the expression level of TMPO in GBM specimens. Then the expression of TMPO was knocked down in GBM cells using lentiviral system, and the knockdown efficacy was further validated by real-time quantitative PCR and western blot analysis. Furthermore, the effects of TMPO silencing on GBM cell proliferation and apoptosis were examined by MTT, colony formation, and flow cytometry analysis. Meanwhile, the expression of apoptotic markers caspase-3 and poly(ADP-ribose) polymerase (PARP) were investigated by western blot analysis.

Results

This study observed that the expression of TMPO in GBM specimens was remarkably higher than that in normal brain specimens. Moreover, knockdown of TMPO could significantly inhibit cell proliferation and arrest cell cycle progression at the G2/M phase. It also found that TMPO knockdown promoted cell apoptosis by upregulation of the cleavage of caspase-3 and PARP protein levels which are the markers of apoptosis.

Conclusions

The results suggested TMPO might be a novel therapeutic target for GBM.

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Safety and efficacy of the keystone and rhomboid flaps for immediate reconstruction after wide local excision of non-head and neck melanomas

Abstract

Background

After wide local excision of cutaneous melanoma, large defects not amenable to simple primary closure are often covered with skin grafts. We report our experience using the rhomboid and keystone flaps to immediately close large axial and extremity wounds after potentially curative surgery for non-head and neck melanomas.

Methods

Between January 2011 and September 2016, demographic, operative, pathologic, and outcome data were prospectively collected on 60 patients who underwent wide local excision of melanoma followed by immediate flap reconstruction. Flaps were of either rhomboid or keystone type. Chi-square analysis was used to compare relationships between factors.

Results

All procedures were done by the senior author and as outpatient surgery. No patient required a surgical drain unless they were undergoing concomitant radical regional node dissection. Flap separation (arbitrarily defined as a >5-mm dehiscence of the suture line) occurred in 16/61 patients (26 %). No patient had flap loss. The risk of flap morbidity was significantly higher if the primary tumor was on the distal extremity—10 of 24 patients (42 %), all with keystone flaps—than if it was on the trunk or the proximal extremity (6/37 patients, 16 %), p = 0.04. There were no margins positive for either invasive or in situ melanoma in the entire cohort.

Conclusions

Simple transposition flaps can successfully cover large defects after melanoma excision without the need for skin grafting. Keystone flaps in the distal extremity are more prone to separation, but this is minor and does not result in flap loss. There is minimal risk of a positive margin requiring flap takedown and a second re-excision.

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Depletion of thymopoietin inhibits proliferation and induces cell cycle arrest/apoptosis in glioblastoma cells

Abstract

Background

Glioblastoma (GBM) is the most malignant nervous system tumor with an almost 100 % recurrence rate. Thymopoietin (TMPO) has been demonstrated to be upregulated in various tumors, including lung cancer, breast cancer, and so on, but its role in GBM has not been reported. This study was aimed to determine the role of TMPO in GBM.

Methods

Publicly available Oncomine dataset analysis was used to explore the expression level of TMPO in GBM specimens. Then the expression of TMPO was knocked down in GBM cells using lentiviral system, and the knockdown efficacy was further validated by real-time quantitative PCR and western blot analysis. Furthermore, the effects of TMPO silencing on GBM cell proliferation and apoptosis were examined by MTT, colony formation, and flow cytometry analysis. Meanwhile, the expression of apoptotic markers caspase-3 and poly(ADP-ribose) polymerase (PARP) were investigated by western blot analysis.

Results

This study observed that the expression of TMPO in GBM specimens was remarkably higher than that in normal brain specimens. Moreover, knockdown of TMPO could significantly inhibit cell proliferation and arrest cell cycle progression at the G2/M phase. It also found that TMPO knockdown promoted cell apoptosis by upregulation of the cleavage of caspase-3 and PARP protein levels which are the markers of apoptosis.

Conclusions

The results suggested TMPO might be a novel therapeutic target for GBM.

http://ift.tt/2dn7895

Safety and efficacy of the keystone and rhomboid flaps for immediate reconstruction after wide local excision of non-head and neck melanomas

Abstract

Background

After wide local excision of cutaneous melanoma, large defects not amenable to simple primary closure are often covered with skin grafts. We report our experience using the rhomboid and keystone flaps to immediately close large axial and extremity wounds after potentially curative surgery for non-head and neck melanomas.

Methods

Between January 2011 and September 2016, demographic, operative, pathologic, and outcome data were prospectively collected on 60 patients who underwent wide local excision of melanoma followed by immediate flap reconstruction. Flaps were of either rhomboid or keystone type. Chi-square analysis was used to compare relationships between factors.

Results

All procedures were done by the senior author and as outpatient surgery. No patient required a surgical drain unless they were undergoing concomitant radical regional node dissection. Flap separation (arbitrarily defined as a >5-mm dehiscence of the suture line) occurred in 16/61 patients (26 %). No patient had flap loss. The risk of flap morbidity was significantly higher if the primary tumor was on the distal extremity—10 of 24 patients (42 %), all with keystone flaps—than if it was on the trunk or the proximal extremity (6/37 patients, 16 %), p = 0.04. There were no margins positive for either invasive or in situ melanoma in the entire cohort.

Conclusions

Simple transposition flaps can successfully cover large defects after melanoma excision without the need for skin grafting. Keystone flaps in the distal extremity are more prone to separation, but this is minor and does not result in flap loss. There is minimal risk of a positive margin requiring flap takedown and a second re-excision.

http://ift.tt/2e10pjc

Effectiveness of postoperative elemental diet (Elental®) in elderly patients after gastrectomy

Abstract

Background

We aimed to investigate the efficacy of postoperative early intervention with an elemental diet to reduce weight loss and enhance recovery after gastrectomy. Nutritional status and gastrointestinal immune function tend to worsen, and postoperative weight loss is inevitable in these patients; therefore, improvement in their postoperative condition is important, especially in gastric cancer patients aged ≥80 years.

Methods

Clinical outcomes and postoperative nutritional status were compared between 21 and 22 consecutive elderly patients aged ≥80 years who underwent distal gastrectomy before and after the introduction of postoperative oral elemental diet (Elental®, 300 kcal/day), respectively, between October 2011 and June 2016.

Results

A significant reduction in postoperative complications was noted in the nutrition support group (N-group) as compared with the control group (C-group). In particular, the prevalence of systemic complications was significantly lower in the N-group (33.3 vs. 4.5 %, p = 0.015), whereas no significant difference was observed in the prevalence of locoregional complications. The percentage of weight loss and reduction in BMI from 1 month to 1 year after surgery was significantly lower in the N-group (p = 0.012 each). The nutrition status (albumin, total protein, hemoglobin, and C-reactive protein levels) at 1 month after surgery showed improvements (p = 0.005, p = 0.048), and hospital stay was decreased in the N-group as compared to the C-group (16.0 vs. 12.5 days, p = 0.041).

Conclusions

Early intervention with an elemental diet after distal gastrectomy is valuable for reducing perioperative weight loss and improving nutritional management and may be associated with enhanced postoperative recovery in elderly patients.

http://ift.tt/2dn8wsC

Outcome and the effect of age and socioeconomic status in 1318 patients with synovial sarcoma in the English National Cancer Registry: 1985–2009

Abstract

Background

The role of age as a prognostic factor has been examined in single institutional studies and in larger data sets from the SEER database, showing a survival advantage for younger versus adult patients with synovial sarcoma (SS). To further assess the role of age, socioeconomic status and other prognostic factors on outcome for SS, we analysed a contemporary all-age population-based cohort of patients with SS registered in England.

Methods

The data on 1318 synovial sarcomas diagnosed in England between 1985 and 2009 were retrospectively analysed for incidence, and the effect of age, patient characteristics and deprivation on outcome using both univariate and multivariate analysis.

Results

The incidence of SS increased to 1.4 per million over the time period, the numbers diagnosed in patients under 10 years of age were small. The site or incidence of metastases did not vary between age groups. There were, however, significant differences (p < 0.05) in the 5-year relative survival rates between patients aged 0–19 years and those ≥20 years of age, 76 % and 53 % respectively. Survival was better in localised tumours at an extremity site. In multivariate analysis higher mortality occurred in older patients, non-extremity site, presence of metastases, female adults and a higher deprivation score.

Conclusions

Synovial sarcoma in children/teenagers compared with adults, have a similar clinical presentation in this population-based series, but a superior outcome. The finding of socioeconomic deprivation affecting outcome in SS needs further exploration in a complete and contemporary dataset, where all prognostic variables are present.

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Outcome and the effect of age and socioeconomic status in 1318 patients with synovial sarcoma in the English National Cancer Registry: 1985–2009

Abstract

Background

The role of age as a prognostic factor has been examined in single institutional studies and in larger data sets from the SEER database, showing a survival advantage for younger versus adult patients with synovial sarcoma (SS). To further assess the role of age, socioeconomic status and other prognostic factors on outcome for SS, we analysed a contemporary all-age population-based cohort of patients with SS registered in England.

Methods

The data on 1318 synovial sarcomas diagnosed in England between 1985 and 2009 were retrospectively analysed for incidence, and the effect of age, patient characteristics and deprivation on outcome using both univariate and multivariate analysis.

Results

The incidence of SS increased to 1.4 per million over the time period, the numbers diagnosed in patients under 10 years of age were small. The site or incidence of metastases did not vary between age groups. There were, however, significant differences (p < 0.05) in the 5-year relative survival rates between patients aged 0–19 years and those ≥20 years of age, 76 % and 53 % respectively. Survival was better in localised tumours at an extremity site. In multivariate analysis higher mortality occurred in older patients, non-extremity site, presence of metastases, female adults and a higher deprivation score.

Conclusions

Synovial sarcoma in children/teenagers compared with adults, have a similar clinical presentation in this population-based series, but a superior outcome. The finding of socioeconomic deprivation affecting outcome in SS needs further exploration in a complete and contemporary dataset, where all prognostic variables are present.

http://ift.tt/2eQYe4n

18F-fludrodeoxyglucose maximal standardized uptake value and metabolic tumor burden are associated with major chemotherapy-related tumor markers in NSCLC patients

http://ift.tt/2dqegNl

Comparison of the efficacy and tolerability of gefitinib with pemetrexed maintenance after first-line platinum-based doublet chemotherapy in advanced lung adenocarcinoma: single-center experience

http://ift.tt/2ekl59m

Prognostic value of fever grade combined with neutrophil percentage in hepatocellular carcinoma patients presenting fever as the initial manifestation

http://ift.tt/2dqdCzi

Identification of two distinct mesenchymal stromal cell populations in human malignant glioma

Abstract

Gene profiling has revealed that malignant gliomas can be divided into four distinct molecular subtypes, where tumors with a mesenchymal gene expression are correlated with short survival. The present investigation was undertaken to clarify whether human malignant gliomas contain endogenous mesenchymal stromal cells (MSC), fulfilling consensus criteria defined by The International Society for Cellular Therapy, recruited from the host. We found that MSC-like cells can be isolated from primary human malignant gliomas. Two distinct MSC-like cell populations, differing in their expression of the CD90 surface marker, were discovered after cell sorting. RNA sequencing revealed further genetic differences between these two cell populations and MSC-like cells lacking CD90 produced higher amounts of VEGF and PGE₂ compared to cells with the true MSC phenotype, implying that the CD90⁻ MSC-like cells most probably are more active in tumor vascularization and immunosuppression than their CD90⁺ counterpart. The results highlight the CD90⁻ subpopulation as an important tumor component, however, its functional effects in glioma remains to be resolved. Using the protocols presented here, it will be possible to isolate, characterize and analyze brain tumor-derived MSC-like cells in more detail and to further test their functions in vitro and in in vivo xenograft models of glioma.

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Outcome of patients affected by newly diagnosed glioblastoma undergoing surgery assisted by 5-aminolevulinic acid guided resection followed by BCNU wafers implantation: a 3-year follow-up

Abstract

The purpose of the study was to evaluate the clinical outcome of the association of BCNU wafers implantation and 5-aminolevulinic acid (5-ALA) fluorescence in the treatment of patients with newly diagnosed glioblastoma (ndGBM). Clinical and surgical data from patients who underwent 5-ALA surgery followed by BCNU wafers implantation were retrospectively evaluated (20 patients, Group I) and compared with data of patients undergoing surgery with BCNU wafers alone (42 patients, Group II) and 5-ALA alone (59 patients, Group III). Patients undergoing 5-ALA assisted resection followed by BCNU wafers implantation (Group I) resulted long survivors (>3 years) in 15 % of cases and showed a median PFS and MS of 11 and 22 months, respectively. Patients treated with BCNU wafers presented a significantly higher survival when tumor was removed with the assistance of 5-ALA (22 months with vs 18 months without 5-ALA, p < 0.0001); these data could be partially explained by the significantly higher CRET achieved in patients operated with 5-ALA assistance (80 % with vs 47 %% without 5-ALA). Moreover, patients of Group I showed a significant increased survival compared with Group III (5-ALA without BCNU) (22 months with vs 21 months without BCNU wafers, p = 0.0025) even with a comparable CRET (80 % vs 76 %, respectively). The occurrence of adverse events related to wafers did not significantly increase with 5-ALA (20 % with and 19 % without 5-ALA) and did not impact in survival outcome. In conclusion, our experience shows that on selected ndGBM patients 5-ALA technology and BCNU wafers implantation show a synergic action on patients' outcome without increasing adverse events occurrence.

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Anticancer potential of diarylidenyl piperidone derivatives, HO-4200 and H-4318, in cisplatin resistant primary ovarian cancer

Volume 17, Issue 10, October 2016, Page 1107-1115
.


http://ift.tt/2dqdgIV

Identification of two distinct mesenchymal stromal cell populations in human malignant glioma

Abstract

Gene profiling has revealed that malignant gliomas can be divided into four distinct molecular subtypes, where tumors with a mesenchymal gene expression are correlated with short survival. The present investigation was undertaken to clarify whether human malignant gliomas contain endogenous mesenchymal stromal cells (MSC), fulfilling consensus criteria defined by The International Society for Cellular Therapy, recruited from the host. We found that MSC-like cells can be isolated from primary human malignant gliomas. Two distinct MSC-like cell populations, differing in their expression of the CD90 surface marker, were discovered after cell sorting. RNA sequencing revealed further genetic differences between these two cell populations and MSC-like cells lacking CD90 produced higher amounts of VEGF and PGE₂ compared to cells with the true MSC phenotype, implying that the CD90⁻ MSC-like cells most probably are more active in tumor vascularization and immunosuppression than their CD90⁺ counterpart. The results highlight the CD90⁻ subpopulation as an important tumor component, however, its functional effects in glioma remains to be resolved. Using the protocols presented here, it will be possible to isolate, characterize and analyze brain tumor-derived MSC-like cells in more detail and to further test their functions in vitro and in in vivo xenograft models of glioma.

http://ift.tt/2eP0E3j

Outcome of patients affected by newly diagnosed glioblastoma undergoing surgery assisted by 5-aminolevulinic acid guided resection followed by BCNU wafers implantation: a 3-year follow-up

Abstract

The purpose of the study was to evaluate the clinical outcome of the association of BCNU wafers implantation and 5-aminolevulinic acid (5-ALA) fluorescence in the treatment of patients with newly diagnosed glioblastoma (ndGBM). Clinical and surgical data from patients who underwent 5-ALA surgery followed by BCNU wafers implantation were retrospectively evaluated (20 patients, Group I) and compared with data of patients undergoing surgery with BCNU wafers alone (42 patients, Group II) and 5-ALA alone (59 patients, Group III). Patients undergoing 5-ALA assisted resection followed by BCNU wafers implantation (Group I) resulted long survivors (>3 years) in 15 % of cases and showed a median PFS and MS of 11 and 22 months, respectively. Patients treated with BCNU wafers presented a significantly higher survival when tumor was removed with the assistance of 5-ALA (22 months with vs 18 months without 5-ALA, p < 0.0001); these data could be partially explained by the significantly higher CRET achieved in patients operated with 5-ALA assistance (80 % with vs 47 %% without 5-ALA). Moreover, patients of Group I showed a significant increased survival compared with Group III (5-ALA without BCNU) (22 months with vs 21 months without BCNU wafers, p = 0.0025) even with a comparable CRET (80 % vs 76 %, respectively). The occurrence of adverse events related to wafers did not significantly increase with 5-ALA (20 % with and 19 % without 5-ALA) and did not impact in survival outcome. In conclusion, our experience shows that on selected ndGBM patients 5-ALA technology and BCNU wafers implantation show a synergic action on patients' outcome without increasing adverse events occurrence.

http://ift.tt/2eq32JC

Association of the germline BRCA2 missense variation Glu2663Lys with high sensitivity to trabectedin-based treatment in soft tissue sarcoma

Volume 17, Issue 10, October 2016, Page 1017-1021
.


http://ift.tt/2ekiqfP

Association of the germline BRCA2 missense variation Glu2663Lys with high sensitivity to trabectedin-based treatment in soft tissue sarcoma

Volume 17, Issue 10, October 2016, Page 1017-1021
.


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Anticancer potential of diarylidenyl piperidone derivatives, HO-4200 and H-4318, in cisplatin resistant primary ovarian cancer

Volume 17, Issue 10, October 2016, Page 1107-1115
.


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RARγ-induced E-cadherin downregulation promotes hepatocellular carcinoma invasion and metastasis

Abstract

Background

Aberrant expression of Retinoic acid receptor γ (RARγ) is implicated in cancer development. Our previous study identified that RARγ functions as a tumor promoter to drive hepatocellular carcinoma (HCC) growth. However, its contribution to HCC invasion and metastasis remains unclear.

Methods

RARγ expression in clinical HCC samples was detected by western blot and immunohistochemistry. The relationship between RARγ expression levels and the clinical characteristics were evaluated. HCC cell line MHCC-97H were stably knocked down RARγ using a lentivirus vector-based shRNA technique. The cells were analyzed by migration and invasion assays, and injected into nude mice to assess tumor metastasis. E-cadherin expression regulated by RARγ was examined by qPCR, western blot and immunofluorescence staining.

Results

The expression of RARγ is significantly upregulated in human HCC tissues. Moreover, its expression positively correlates with tumor size, distant metastasis and TNM stage, and negatively correlates with length of survival of HCC patients. Knockdown of RARγ markedly inhibits HCC cell invasion and metastasis both in vitro and in vivo. Mechanistic investigations reveal that RARγ functions through regulation of NF-κB-mediated E-cadherin downregulation to promote HCC invasion and metastasis. Notably, RARγ expression status negatively correlates with E-cadherin expression in HCC cell lines and clinical HCC samples.

Conclusions

These findings demonstrate that RARγ could promote HCC invasion and metastasis by regulating E-cadherin reduction, and implicate new strategies to aggressively treat HCC through targeting RARγ/E-cadherin signaling axis.

http://ift.tt/2e0NE8l

RARγ-induced E-cadherin downregulation promotes hepatocellular carcinoma invasion and metastasis

Abstract

Background

Aberrant expression of Retinoic acid receptor γ (RARγ) is implicated in cancer development. Our previous study identified that RARγ functions as a tumor promoter to drive hepatocellular carcinoma (HCC) growth. However, its contribution to HCC invasion and metastasis remains unclear.

Methods

RARγ expression in clinical HCC samples was detected by western blot and immunohistochemistry. The relationship between RARγ expression levels and the clinical characteristics were evaluated. HCC cell line MHCC-97H were stably knocked down RARγ using a lentivirus vector-based shRNA technique. The cells were analyzed by migration and invasion assays, and injected into nude mice to assess tumor metastasis. E-cadherin expression regulated by RARγ was examined by qPCR, western blot and immunofluorescence staining.

Results

The expression of RARγ is significantly upregulated in human HCC tissues. Moreover, its expression positively correlates with tumor size, distant metastasis and TNM stage, and negatively correlates with length of survival of HCC patients. Knockdown of RARγ markedly inhibits HCC cell invasion and metastasis both in vitro and in vivo. Mechanistic investigations reveal that RARγ functions through regulation of NF-κB-mediated E-cadherin downregulation to promote HCC invasion and metastasis. Notably, RARγ expression status negatively correlates with E-cadherin expression in HCC cell lines and clinical HCC samples.

Conclusions

These findings demonstrate that RARγ could promote HCC invasion and metastasis by regulating E-cadherin reduction, and implicate new strategies to aggressively treat HCC through targeting RARγ/E-cadherin signaling axis.

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Cancers, Vol. 8, Pages 95: Functional Roles of E6 and E7 Oncoproteins in HPV-Induced Malignancies at Diverse Anatomical Sites

Approximately 200 human papillomaviruses (HPVs) infect human epithelial cells, of which the alpha and beta types have been the most extensively studied. Alpha HPV types mainly infect mucosal epithelia and a small group of these causes over 600,000 cancers per year worldwide at various anatomical sites, especially anogenital and head-and-neck cancers. Of these the most important is cervical cancer, which is the leading cause of cancer-related death in women in many parts of the world. Beta HPV types infect cutaneous epithelia and may contribute towards the initiation of non-melanoma skin cancers. HPVs encode two oncoproteins, E6 and E7, which are directly responsible for the development of HPV-induced carcinogenesis. They do this cooperatively by targeting diverse cellular pathways involved in the regulation of cell cycle control, of apoptosis and of cell polarity control networks. In this review, the biological consequences of papillomavirus targeting of various cellular substrates at diverse anatomical sites in the development of HPV-induced malignancies are highlighted.

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Cancers, Vol. 8, Pages 95: Functional Roles of E6 and E7 Oncoproteins in HPV-Induced Malignancies at Diverse Anatomical Sites

Approximately 200 human papillomaviruses (HPVs) infect human epithelial cells, of which the alpha and beta types have been the most extensively studied. Alpha HPV types mainly infect mucosal epithelia and a small group of these causes over 600,000 cancers per year worldwide at various anatomical sites, especially anogenital and head-and-neck cancers. Of these the most important is cervical cancer, which is the leading cause of cancer-related death in women in many parts of the world. Beta HPV types infect cutaneous epithelia and may contribute towards the initiation of non-melanoma skin cancers. HPVs encode two oncoproteins, E6 and E7, which are directly responsible for the development of HPV-induced carcinogenesis. They do this cooperatively by targeting diverse cellular pathways involved in the regulation of cell cycle control, of apoptosis and of cell polarity control networks. In this review, the biological consequences of papillomavirus targeting of various cellular substrates at diverse anatomical sites in the development of HPV-induced malignancies are highlighted.

http://ift.tt/2dNDne4

Means to the ends: The role of telomeres and telomere processing machinery in metastasis

Publication date: Available online 18 October 2016
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Nathaniel J. Robinson, William P. Schiemann
Despite significant clinical advancements, cancer remains a leading cause of mortality throughout the world due largely to the process of metastasis and the dissemination of cancer cells from their primary tumor of origin to distant secondary sites. The clinical burden imposed by metastasis is further compounded by a paucity of information regarding the factors that mediate metastatic progression. Linear chromosomes are capped by structures known as telomeres, which dictate cellular lifespan in humans by shortening progressively during successive cell divisions. Although telomere shortening occurs in nearly all somatic cells, telomeres may be elongated via two seemingly disjoint pathways: (i) telomerase-mediated extension, and (ii) homologous recombination-based alternative lengthening of telomeres (ALT). Both telomerase and ALT are activated in various human cancers, with more recent evidence implicating both pathways as potential mediators of metastasis. Here we review the known roles of telomere homeostasis in metastasis and posit a mechanism whereby metastatic activity is determined by a dynamic fluctuation between ALT and telomerase, as opposed to the mere activation of a generic telomere elongation program. Additionally, the pleiotropic nature of the telomere processing machinery makes it an attractive therapeutic target for metastasis, and as such, we also explore the therapeutic implications of our proposed mechanism.



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The importance of stress management among postresection breast cancer patients

Future Oncology Ahead of Print.


http://ift.tt/2dmDErX

The importance of stress management among postresection breast cancer patients

Future Oncology Ahead of Print.


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Moving Toward Improved Teamwork in Cancer Care: The Role of Psychological Safety in Team Communication [Original Contribution]

Effective communication is a requirement in the teamwork necessary for improved coordination to deliver patient-centered, value-based cancer care. Communication is particularly important when care providers are geographically distributed or work across organizations. We review organizational and teams research on communication to highlight psychological safety as a key determinant of high-quality communication within teams. We first present the concept of psychological safety, findings about its communication effects for teamwork, and factors that affect it. We focus on five factors applicable to cancer care delivery: familiarity, clinical hierarchy–related status differences, geographic dispersion, boundary spanning, and leader behavior. To illustrate how these factors facilitate or hinder psychologically safe communication and teamwork in cancer care, we review the case of a patient as she experiences the treatment-planning process for early-stage breast cancer in a community setting. Our analysis is summarized in a key principle: Teamwork in cancer care requires high-quality communication, which depends on psychological safety for all team members, clinicians and patients alike. We conclude with a discussion of the implications of psychological safety in clinical care and suggestions for future research.

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Team Science in Cancer Care: Questions, an Observation, and a Caution [Editorial]

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Transforming Prior Authorization to Decision Support [Business of Oncology]

Purpose:

To evaluate a computer-based prior authorization system that was designed to include and test two new concepts for physician review: (1) the tool would minimize denials by providing real-time decision support with alternative options if the original request was noncompliant, and (2) the tool would collect sufficient information to create a patient registry.

Methods:

A new prior authorization tool incorporating real-time decision support was tested with a large national payer. The tool used the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology as the content for decision making. Physicians were asked to submit the minimal amount of clinical data necessary to reach a treatment-decision node within the National Comprehensive Cancer Network Guidelines. To minimize denials, all available recommended treatments were displayed for physician consideration and immediate authorization was granted for any compliant selection.

Results:

During a 1-year pilot in a Florida commercial health plan, 4,272 eligible cases were reviewed with only 42 denials. Chemotherapy drug costs for the prior authorization pilot were compared with a similar time period in the previous year for the state of Florida, as well as for the Southeast region and for the nation, which served as controls. The percentage change between the time periods was –9% in Florida, 10% for the national costs, and 11% for the Southeast region costs. The difference between the regional increase and the Florida decrease represented a savings of $5.3 million dollars for the state of Florida in 1 year.

Conclusion:

There is significant opportunity to reduce the costs of therapy while being compliant with nationally accepted guidelines for cancer chemotherapy.

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National Cancer Institute-American Society of Clinical Oncology Teams in Cancer Care Project [Introduction]

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Moving Toward Improved Teamwork in Cancer Care: The Role of Psychological Safety in Team Communication [Original Contribution]

Effective communication is a requirement in the teamwork necessary for improved coordination to deliver patient-centered, value-based cancer care. Communication is particularly important when care providers are geographically distributed or work across organizations. We review organizational and teams research on communication to highlight psychological safety as a key determinant of high-quality communication within teams. We first present the concept of psychological safety, findings about its communication effects for teamwork, and factors that affect it. We focus on five factors applicable to cancer care delivery: familiarity, clinical hierarchy–related status differences, geographic dispersion, boundary spanning, and leader behavior. To illustrate how these factors facilitate or hinder psychologically safe communication and teamwork in cancer care, we review the case of a patient as she experiences the treatment-planning process for early-stage breast cancer in a community setting. Our analysis is summarized in a key principle: Teamwork in cancer care requires high-quality communication, which depends on psychological safety for all team members, clinicians and patients alike. We conclude with a discussion of the implications of psychological safety in clinical care and suggestions for future research.

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Team Science in Cancer Care: Questions, an Observation, and a Caution [Editorial]

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Transforming Prior Authorization to Decision Support [Business of Oncology]

Purpose:

To evaluate a computer-based prior authorization system that was designed to include and test two new concepts for physician review: (1) the tool would minimize denials by providing real-time decision support with alternative options if the original request was noncompliant, and (2) the tool would collect sufficient information to create a patient registry.

Methods:

A new prior authorization tool incorporating real-time decision support was tested with a large national payer. The tool used the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology as the content for decision making. Physicians were asked to submit the minimal amount of clinical data necessary to reach a treatment-decision node within the National Comprehensive Cancer Network Guidelines. To minimize denials, all available recommended treatments were displayed for physician consideration and immediate authorization was granted for any compliant selection.

Results:

During a 1-year pilot in a Florida commercial health plan, 4,272 eligible cases were reviewed with only 42 denials. Chemotherapy drug costs for the prior authorization pilot were compared with a similar time period in the previous year for the state of Florida, as well as for the Southeast region and for the nation, which served as controls. The percentage change between the time periods was –9% in Florida, 10% for the national costs, and 11% for the Southeast region costs. The difference between the regional increase and the Florida decrease represented a savings of $5.3 million dollars for the state of Florida in 1 year.

Conclusion:

There is significant opportunity to reduce the costs of therapy while being compliant with nationally accepted guidelines for cancer chemotherapy.

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National Cancer Institute-American Society of Clinical Oncology Teams in Cancer Care Project [Introduction]

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RARγ-induced E-cadherin downregulation promotes hepatocellular carcinoma invasion and metastasis

Aberrant expression of Retinoic acid receptor γ (RARγ) is implicated in cancer development. Our previous study identified that RARγ functions as a tumor promoter to drive hepatocellular carcinoma (HCC) growth....

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Spheres derived from the human SN12C renal cell carcinoma cell line are enriched in tumor initiating cells

Recently, tumor initiating cells (TICs), which possess self-renewal and other stem cell properties, are regarded as the cause of tumor initiation, recurrence and metastasis. The isolation and identification of...

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hERG1 positivity and Glut-1 negativity identifies high-risk TNM stage I and II colorectal cancer patients, regardless of adjuvant chemotherapy

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Rare frequency of gene variation and survival analysis in thymic epithelial tumors

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Sensitivity value of hematological markers in patients receiving chemoradiotherapy for esophageal squamous cell carcinoma

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The importance of stress management among postresection breast cancer patients

Future Oncology Ahead of Print.


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The Role of CD90 in the Differential Diagnosis of Pleural Malignant Mesothelioma, Pulmonary Carcinoma and Comparison with Calretının

Abstract

Pleural Malignant Mesothelioma (MM) is a fatal disease that has been associated with asbestos exposure. Differential diagnosis between the pleural infiltration of pulmonary carcinomas and MM is rather difficult particularly for epitheloid type mesothelioma.We aimed to investigate the utility of CD90, a cancer stem cell marker, in the differential diagnosis of MM and lung carcinoma, its prognostic significance and compare its value with that of Calretinin. Ninety pathology specimens including MM (n:30), pulmonary adenocarcinoma (n:30) and pulmonary squamous cell carcinoma (n:30) were used in this study. Immunohistochemical comparision of CD 90 and Calretinin was made in all groups. Calretinin was positive in 20 cases with MM (64.5 %), and was negative in 10 (32.3 %). CD 90 was positive in 25 of these cases (80 %) and negative in 5 (16 %). On the other hand pulmonary adenocarcinomas and squamous cell carcinomas showed positivity with CD90, 63,6 % and 73 %, respectively. We think that CD 90 has no place in the differential diagnosis between mesothelioma and pulmonary carcinoma because of the low specificity in spite of the high sensitivity.

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The Role of CD90 in the Differential Diagnosis of Pleural Malignant Mesothelioma, Pulmonary Carcinoma and Comparison with Calretının

Abstract

Pleural Malignant Mesothelioma (MM) is a fatal disease that has been associated with asbestos exposure. Differential diagnosis between the pleural infiltration of pulmonary carcinomas and MM is rather difficult particularly for epitheloid type mesothelioma.We aimed to investigate the utility of CD90, a cancer stem cell marker, in the differential diagnosis of MM and lung carcinoma, its prognostic significance and compare its value with that of Calretinin. Ninety pathology specimens including MM (n:30), pulmonary adenocarcinoma (n:30) and pulmonary squamous cell carcinoma (n:30) were used in this study. Immunohistochemical comparision of CD 90 and Calretinin was made in all groups. Calretinin was positive in 20 cases with MM (64.5 %), and was negative in 10 (32.3 %). CD 90 was positive in 25 of these cases (80 %) and negative in 5 (16 %). On the other hand pulmonary adenocarcinomas and squamous cell carcinomas showed positivity with CD90, 63,6 % and 73 %, respectively. We think that CD 90 has no place in the differential diagnosis between mesothelioma and pulmonary carcinoma because of the low specificity in spite of the high sensitivity.

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Hyperfractionated Accelerated Reirradiation for Patients With Recurrent Anal Cancer Previously Treated With Definitive Chemoradiation.

Objectives: Although chemoradiation is the standard of care for anal cancer, limited data exist regarding pelvic reirradiation (re-RT) for recurrent disease. We investigated toxicity and outcomes in patients who received prior pelvic radiation therapy (RT), and subsequently underwent hyperfractionated accelerated re-RT to the pelvis for recurrent anal cancer. Materials and Methods: We reviewed records of 10 patients with recurrent anal squamous cell carcinoma who previously received pelvic RT to at least 30 Gy as a component of their chemoradiation and underwent re-RT in 1.5 Gy twice daily fractions to the pelvis, with either preoperative (N=7) or definitive (N=3) intent. Results: The 3-year disease-free survival and 3-year overall survival rates were 40% and 60%. Four patients recurred within the reirradiated field, with a 3-year freedom from local progression rate of 56%. Of the 7 patients treated with preoperative intent, 5 proceeded to surgery, of whom 3 are alive and disease-free at a median duration of 43 months. Of the 3 patients treated definitively with no surgery, all are alive and disease-free at a median duration of 84 months. Re-RT resulted in one grade 3 acute toxicity and no grade 3 or higher late complications. Conclusions: Hyperfractionated accelerated re-RT was well-tolerated in patients with previously irradiated anal cancer. Patients treated with either definitive re-RT or re-RT followed by surgical resection had excellent rates of overall survival and freedom from local progression. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Intraoperative Radiotherapy in the Era of Intensive Neoadjuvant Chemotherapy and Chemoradiotherapy for Pancreatic Adenocarcinoma.

Objectives: Improved outcomes with FOLFIRINOX or gemcitabine with nab-paclitaxel in the treatment of metastatic pancreatic adenocarcinoma (PDAC) have prompted incorporation of these regimens into neoadjuvant treatment of locally advanced unresectable PDAC. Whereas some patients remain unresectable on surgical exploration, others are able to undergo resection after intensive neoadjuvant treatment. We evaluated outcomes and toxicity associated with use of intensive neoadjuvant treatment followed by intraoperative radiotherapy (IORT) in combination with resection or exploratory laparotomy. Methods: We retrospectively analyzed patients with locally advanced unresectable or borderline-resectable PDAC who received intensive neoadjuvant treatment with induction chemotherapy and chemoradiotherapy followed by exploratory laparotomy in an IORT-equipped operating suite between 2010 and 2015. Surgical outcomes and overall survival (OS) were compared. Results: Of 68 patients, 41 (60.3%) underwent resection, 18 (26.5%) had unresectable disease, and 9 (13.2%) had distant metastases. Of 41 resectable patients, 22 received IORT for close/positive resection margins on intraoperative frozen section. There was no significant difference in operative times or morbidity with addition of IORT to resection. Median OS was 26.6 months for all patients who underwent resection, 35.1 months for patients who underwent resection and IORT, and 24.5 months for patients who underwent resection alone (P=NS). Of 18 patients with unresectable disease, all but 1 received IORT, with median OS of 24.8 months. IORT was associated with increased hospital stay (4 vs. 3.5 d), but no significant difference in operative times or morbidity. Conclusions: IORT in addition to intensive neoadjuvant chemotherapy and chemoradiotherapy was not associated with increased toxicity when used with resection or exploratory laparotomy, and was associated with encouraging survival rates in patients with close/positive margins and patients with unresectable disease. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Clinical and Economic Evaluation of Treatment Strategies for T1N0 Anal Canal Cancer.

Objective: A comparative assessment of treatment alternatives for T1N0 anal canal cancer has never been conducted. We compared the outcomes associated with the treatment alternatives-chemoradiotherapy (CRT), radiotherapy (RT), and surgery or ablation techniques (surgery/ablation)-for T1N0 anal canal cancer. Materials and Methods: This retrospective cohort study was conducted using the Surveillance, Epidemiology and End Results (SEER) registries linked with Medicare longitudinal data (SEER-Medicare database). Analysis included 190 patients who were treated for T1N0 anal canal cancer using surgery/ablation (n=44), RT (n=50), or CRT (n=96). The outcomes were reported in terms of survival and hazards ratios using Kaplan-Meier and Cox proportional hazards modeling, respectively; lifetime costs; and cost-effectiveness measured in terms of incremental cost-effectiveness ratio, that is, the ratio of the difference in costs between the 2 alternatives to the difference in effectiveness between the same 2 alternatives. Results: There was no significant difference in the survival duration between the treatment groups as predicted by the Kaplan-Meier curves. After adjusting for patient characteristics and propensity score, the hazard ratio of death for the patients who received CRT compared with surgery/ablation was 1.742 (95% confidence interval, 0.793-3.829) and RT was 2.170 (95% confidence interval, 0.923-5.101); however, the relationship did not reach statistical significance. Surgery/ablation resulted in lower lifetime cost than RT or CRT. The incremental cost-effectiveness ratio associated with CRT compared with surgery/ablation was $142,883 per life year gained. Conclusions: There was no statistically significant difference in survival among the treatment alternatives for T1N0 anal canal cancer. Given that surgery/ablation costs less than RT or CRT and might be cost-effective compared with RT and CRT, it is crucial to explore this finding further in this era of limited health care resources. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Hyperfractionated Accelerated Reirradiation for Patients With Recurrent Anal Cancer Previously Treated With Definitive Chemoradiation.

Objectives: Although chemoradiation is the standard of care for anal cancer, limited data exist regarding pelvic reirradiation (re-RT) for recurrent disease. We investigated toxicity and outcomes in patients who received prior pelvic radiation therapy (RT), and subsequently underwent hyperfractionated accelerated re-RT to the pelvis for recurrent anal cancer. Materials and Methods: We reviewed records of 10 patients with recurrent anal squamous cell carcinoma who previously received pelvic RT to at least 30 Gy as a component of their chemoradiation and underwent re-RT in 1.5 Gy twice daily fractions to the pelvis, with either preoperative (N=7) or definitive (N=3) intent. Results: The 3-year disease-free survival and 3-year overall survival rates were 40% and 60%. Four patients recurred within the reirradiated field, with a 3-year freedom from local progression rate of 56%. Of the 7 patients treated with preoperative intent, 5 proceeded to surgery, of whom 3 are alive and disease-free at a median duration of 43 months. Of the 3 patients treated definitively with no surgery, all are alive and disease-free at a median duration of 84 months. Re-RT resulted in one grade 3 acute toxicity and no grade 3 or higher late complications. Conclusions: Hyperfractionated accelerated re-RT was well-tolerated in patients with previously irradiated anal cancer. Patients treated with either definitive re-RT or re-RT followed by surgical resection had excellent rates of overall survival and freedom from local progression. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Intraoperative Radiotherapy in the Era of Intensive Neoadjuvant Chemotherapy and Chemoradiotherapy for Pancreatic Adenocarcinoma.

Objectives: Improved outcomes with FOLFIRINOX or gemcitabine with nab-paclitaxel in the treatment of metastatic pancreatic adenocarcinoma (PDAC) have prompted incorporation of these regimens into neoadjuvant treatment of locally advanced unresectable PDAC. Whereas some patients remain unresectable on surgical exploration, others are able to undergo resection after intensive neoadjuvant treatment. We evaluated outcomes and toxicity associated with use of intensive neoadjuvant treatment followed by intraoperative radiotherapy (IORT) in combination with resection or exploratory laparotomy. Methods: We retrospectively analyzed patients with locally advanced unresectable or borderline-resectable PDAC who received intensive neoadjuvant treatment with induction chemotherapy and chemoradiotherapy followed by exploratory laparotomy in an IORT-equipped operating suite between 2010 and 2015. Surgical outcomes and overall survival (OS) were compared. Results: Of 68 patients, 41 (60.3%) underwent resection, 18 (26.5%) had unresectable disease, and 9 (13.2%) had distant metastases. Of 41 resectable patients, 22 received IORT for close/positive resection margins on intraoperative frozen section. There was no significant difference in operative times or morbidity with addition of IORT to resection. Median OS was 26.6 months for all patients who underwent resection, 35.1 months for patients who underwent resection and IORT, and 24.5 months for patients who underwent resection alone (P=NS). Of 18 patients with unresectable disease, all but 1 received IORT, with median OS of 24.8 months. IORT was associated with increased hospital stay (4 vs. 3.5 d), but no significant difference in operative times or morbidity. Conclusions: IORT in addition to intensive neoadjuvant chemotherapy and chemoradiotherapy was not associated with increased toxicity when used with resection or exploratory laparotomy, and was associated with encouraging survival rates in patients with close/positive margins and patients with unresectable disease. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Clinical and Economic Evaluation of Treatment Strategies for T1N0 Anal Canal Cancer.

Objective: A comparative assessment of treatment alternatives for T1N0 anal canal cancer has never been conducted. We compared the outcomes associated with the treatment alternatives-chemoradiotherapy (CRT), radiotherapy (RT), and surgery or ablation techniques (surgery/ablation)-for T1N0 anal canal cancer. Materials and Methods: This retrospective cohort study was conducted using the Surveillance, Epidemiology and End Results (SEER) registries linked with Medicare longitudinal data (SEER-Medicare database). Analysis included 190 patients who were treated for T1N0 anal canal cancer using surgery/ablation (n=44), RT (n=50), or CRT (n=96). The outcomes were reported in terms of survival and hazards ratios using Kaplan-Meier and Cox proportional hazards modeling, respectively; lifetime costs; and cost-effectiveness measured in terms of incremental cost-effectiveness ratio, that is, the ratio of the difference in costs between the 2 alternatives to the difference in effectiveness between the same 2 alternatives. Results: There was no significant difference in the survival duration between the treatment groups as predicted by the Kaplan-Meier curves. After adjusting for patient characteristics and propensity score, the hazard ratio of death for the patients who received CRT compared with surgery/ablation was 1.742 (95% confidence interval, 0.793-3.829) and RT was 2.170 (95% confidence interval, 0.923-5.101); however, the relationship did not reach statistical significance. Surgery/ablation resulted in lower lifetime cost than RT or CRT. The incremental cost-effectiveness ratio associated with CRT compared with surgery/ablation was $142,883 per life year gained. Conclusions: There was no statistically significant difference in survival among the treatment alternatives for T1N0 anal canal cancer. Given that surgery/ablation costs less than RT or CRT and might be cost-effective compared with RT and CRT, it is crucial to explore this finding further in this era of limited health care resources. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Secondary OSCC Chemoprevention via Multiple Agents

Abstract. Over 1/3 of patients who have undergone oral squamous cell carcinoma (OSCC) surgical resections develop life-threatening and often untreatable recurrences. A variety of drugs, intended for management of recurrent or disseminated cancers, were designed to exploit cancer cells' reliance upon overexpressed receptors and gratuitous signaling. Despite their conceptual promise, clinical trials showed these agents lacked efficacy and were often toxic. These findings are consistent with evasion of pathway-targeted treatments via extensive signaling redundancies and compensatory mechanisms common to cancers. Optimal secondary OSCC chemoprevention requires long term efficacy with multifaceted, nontoxic agents. Accordingly, this study evaluated the abilities of three complementary chemopreventives i.e. the vitamin A derivative fenretinide (4-HPR, induces apoptosis and differentiation, inhibits signaling proteins and invasion), the estrogen metabolite 2-methoxyestradiol (2-ME, apoptosis-inducing, antiangiogenic) and the humanized monoclonal antibody to the IL-6R receptor tocilizumab (TOC, reduces IL-6 signaling) to suppress OSCC gratuitous signaling and tumorigenesis. Modeling studies demonstrated 4-HPR's high affinity binding at STAT3's dimerization site and c-Abl and c-Src ATP-binding kinase sites. Although individual agents suppressed cancer-promoting pathways including STAT3 phosphorylation, STAT3-DNA binding, and production of the trans-signaling enabling sIL-6R, maximal chemopreventive effects were observed with agent combinations. OSCC tumor xenograft studies showed that locally-delivered TOC, TOC+4-HPR and TOC+4-HPR+2-ME treatments all prevented significant tumor growth. Notably, the TOC+4-HPR+2-ME treatment resulted in the smallest overall increase in tumor volume. The selected agents employ diverse mechanisms to disrupt tumorigenesis at multiple venues i.e. intracellular, tumor cell-ECM and tumor microenvironment; beneficial qualities for secondary chemopreventives.

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