Identification of hereditary cancer in the general population: development and validation of a screening questionnaire for obtaining the family history of cancer

Abstract

One of the challenges for Latin American countries is to include in their healthcare systems technologies that can be applied to hereditary cancer detection and management. The aim of the study is to create and validate a questionnaire to identify individuals with possible risk for hereditary cancer predisposition syndromes (HCPS), using different strategies in a Cancer Prevention Service in Brazil. The primary screening questionnaire (PSQ) was developed to identify families at-risk for HCPS. The PSQ was validated using discrimination measures, and the reproducibility was estimated through kappa coefficient. Patients with at least one affirmative answer had the pedigree drawn using three alternative interview approaches: in-person, by telephone, or letter. Validation of these approaches was done. Kappa and intraclass correlation coefficients were used to analyze data's reproducibility considering the presence of clinical criteria for HCPS. The PSQ was applied to a convenience sample of 20,000 women of which 3121 (15.6%) answered at least one affirmative question and 1938 had their pedigrees drawn. The PSQ showed sensitivity and specificity scores of 94.4% and 75%, respectively, and a kappa of 0.64. The strategies for pedigree drawing had reproducibility coefficients of 0.976 and 0.850 for the telephone and letter approaches, respectively. Pedigree analysis allowed us to identify 465 individuals (24.0%) fulfilling at least one clinical criterion for HCPS. The PSQ fulfills its function, allowing the identification of HCPS at-risk families. The use of alternative screening methods may reduce the number of excluded at-risk individuals/families who live in locations where oncogenetic services are not established.

This manuscript describes the creation and validation of a questionnaire to identify individuals with possible risk for hereditary cancer predisposition syndromes (HCPS), using different strategies in a Cancer Prevention Service in Brazil. The questionnaire was applied to a convenience sample of 20,000 women of which 3121 (15.6%) reported the presence of cancer cases in the family and 1938 had their pedigrees drawn. The use of alternative screening methods may reduce the number of excluded at-risk individuals/families who live in locations where oncogenetic services are not established.

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Identification of hereditary cancer in the general population: development and validation of a screening questionnaire for obtaining the family history of cancer

Abstract

One of the challenges for Latin American countries is to include in their healthcare systems technologies that can be applied to hereditary cancer detection and management. The aim of the study is to create and validate a questionnaire to identify individuals with possible risk for hereditary cancer predisposition syndromes (HCPS), using different strategies in a Cancer Prevention Service in Brazil. The primary screening questionnaire (PSQ) was developed to identify families at-risk for HCPS. The PSQ was validated using discrimination measures, and the reproducibility was estimated through kappa coefficient. Patients with at least one affirmative answer had the pedigree drawn using three alternative interview approaches: in-person, by telephone, or letter. Validation of these approaches was done. Kappa and intraclass correlation coefficients were used to analyze data's reproducibility considering the presence of clinical criteria for HCPS. The PSQ was applied to a convenience sample of 20,000 women of which 3121 (15.6%) answered at least one affirmative question and 1938 had their pedigrees drawn. The PSQ showed sensitivity and specificity scores of 94.4% and 75%, respectively, and a kappa of 0.64. The strategies for pedigree drawing had reproducibility coefficients of 0.976 and 0.850 for the telephone and letter approaches, respectively. Pedigree analysis allowed us to identify 465 individuals (24.0%) fulfilling at least one clinical criterion for HCPS. The PSQ fulfills its function, allowing the identification of HCPS at-risk families. The use of alternative screening methods may reduce the number of excluded at-risk individuals/families who live in locations where oncogenetic services are not established.

This manuscript describes the creation and validation of a questionnaire to identify individuals with possible risk for hereditary cancer predisposition syndromes (HCPS), using different strategies in a Cancer Prevention Service in Brazil. The questionnaire was applied to a convenience sample of 20,000 women of which 3121 (15.6%) reported the presence of cancer cases in the family and 1938 had their pedigrees drawn. The use of alternative screening methods may reduce the number of excluded at-risk individuals/families who live in locations where oncogenetic services are not established.

http://ift.tt/2zt1JnN

Procaspase-activating compound-1 induces apoptosis in Trypanosoma cruzi

Abstract

Some therapeutics for parasitic, cardiac and neurological diseases activate apoptosis. Therefore, the study of apoptotic proteins in pathogenic organisms is relevant. However, the molecular mechanism of apoptosis in unicellular organisms remain elusive, despite morphological evidence of its occurrence. In Trypanosoma cruzi, the causative agent of Chagas disease, metacaspase 3 (TcMCA3), seems to have a key role in parasite apoptosis. Accordingly, this work provides data concerning TcMCA3 regulation through its interaction with procaspase-activating compound 1 (PAC-1), a procaspase 3 activator. Indeed, PAC-1 reduced T. cruzi epimastigote viability with an IC₅₀ of 14.12 µM and induced loss of mitochondrial potential and exposure of phosphatidylserine, features of the apoptotic process. Notwithstanding, those PAC-1-inducible effects were not conserved in metacyclic trypomastigotes. Moreover, PAC-1 reduced the viability of mammalian cells with a greater IC₅₀ (25.70 µM) compared to T. cruzi epimastigotes, indicating distinct modes of binding between caspases and metacaspases. To shed light on the selectivity of metacaspases and caspases, we determined the structural features related to the PAC-1 binding sites in both types of proteins. These data are important for improving the understanding of the apoptosis pathway in T. cruzi so that TcMCA3 could be better targeted with future pharmaceuticals.

http://ift.tt/2xWJ8Ef

The Impact of Sentinel Node-Mapping in Staging High-Risk Endometrial Cancer

Abstract

Background

This study aimed to determine the impact of sentinel lymph node (SLN)-mapping on the staging of high-risk endometrial cancer (endometrioid grade 3, serous, clear cell, carcinosarcoma, deep myometrial invasion, or angiolymphatic invasion).

Methods

The study analyzed a series of 236 patients treated at AC Camargo Cancer Center from June 2007 to February 2017. The compared 75 patients who underwent SLN-mapping (SLN group) with 161 patients who received pelvic ± para-aortic lymphadenectomy (N-SLN group). Patients with adnexal, peritoneal, or suspicious node metastases were excluded from the study.

Results

The groups did not differ in terms of age, histologic type, or presence of deep myometrial invasion. The overall detection rate for SLNs was 85.3%, and bilateral SLNs were observed in 60% of the patients. Of 20 positive SLNs, 8 (40%) were detected only after immunohistochemistry (IHC). The findings showed an overall sensitivity of 90%, a negative predictive value of 95.7%, and a false-negative predictive value of 4.3%. The SLN group had more pelvic node metastases detected than the N-SLN group (26.7 vs 14.3%; p = 0.02). However, the rate of para-aortic node metastases did not differ between the two groups (13.5 vs 5.6%; p = 0.12). Five patients (3.5%) in the N-SLN group had isolated para-aortic node metastases versus none in the patients with SLN mapped. Additionally, the SLN group received more adjuvant chemotherapy (48 vs 33.5%; p = 0.03).

Conclusions

The data suggest that SLN-mapping identifies more pelvic node metastases than lymph node dissection alone and increases the node detection rate by 12.5% after IHC. Furthermore, no isolated para-aortic node metastases are observed when SLN is detected.

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Vitamin Status and the Development of Postoperative Cognitive Decline in Elderly Surgical Oncologic Patients

Abstract

Background

This study aimed to evaluate the influence that serum levels of vitamin B12, folate, and homocysteine have on the development of short-term postoperative cognitive decline in the elderly surgical oncology patient.

Methods

This study was part of a prospective cohort study focused on postoperative cognitive outcomes for patients 65 years of age or older undergoing surgery for a solid malignancy. Postoperative cognitive decline was defined as the change in the combined results of the Ruff Figural Fluency Test and the Trail-Making Test Parts A and B. Patients with the highest change in scores 2 weeks postoperatively compared with baseline were considered to be patients with cognitive decline. Patients with the lowest change were considered to be patients without cognitive decline. To analyze the effect of vitamin levels on the changes in postoperative cognitive scores, uni- and multivariate logistic regression analysis were performed.

Results

The study enrolled 61 patients with and 59 patients without postoperative cognitive decline. Hyperhomocysteinemia was present in 14.2% of the patients. Patients with postoperative cognitive decline more often had hyperhomocysteinemia (27.9 vs 10.2%). Hyperhomocysteinemia was associated with a higher chance for the development of postoperative cognitive decline (odds ratio_adjusted, 11.9; 95% confidence interval, 2.4–59.4). Preoperative vitamin B12 or folate deficiency were not associated with the development of postoperative cognitive decline.

Conclusion

Preoperative hyperhomocysteinemia is associated with the development of postoperative cognitive decline. The presence of preoperative hyperhomocysteinemia could be an indicator for an increased risk of postoperative cognitive decline developing in the elderly.

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Performance Analysis of the American Joint Committee on Cancer 8th Edition Staging System for Retroperitoneal Sarcoma and Development of a New Staging Algorithm for Sarcoma-Specific Survival

Abstract

Background

The American Joint Committee on Cancer (AJCC) recently published the 8th edition of the AJCC Cancer Staging Manual. Major changes were made to the staging algorithm for retroperitoneal sarcoma; however, whether these changes improve staging system performance is questionable.

Methods

This retrospective cohort analysis of 3703 adult patients with retroperitoneal sarcoma in the Surveillance, Epidemiology, and End Results (SEER) database compares a novel staging system incorporating histologic subtype of sarcoma with current and prior AJCC soft tissue sarcoma staging systems using multiple statistical techniques. The effect of tumor size on sarcoma-specific survival was also assessed by flexible, non-linear Cox proportional hazard regression using restricted cubic splines and fractional polynomials.

Results

The relationship between the covariate-adjusted log hazard for disease-specific survival and tumor size is non-linear. Although the new AJCC T classification approximates this hazard fairly well, the overall prognostic impact of tumor size is limited after accounting for other predictive factors. Predictive accuracy and concordance indices of the AJCC 8th edition staging system for retroperitoneal sarcoma are significantly lower than the prior 7th edition. A proposed staging system incorporating histologic grade, tumor size, and histologic subtype is superior to both the AJCC 7th and 8th editions in predicting sarcoma-specific survival.

Conclusion

AJCC committees should not revise tumor staging algorithms unless the changes actually improve the staging system. A proposed staging scheme incorporating data regarding histologic subtype of sarcoma performs significantly better than both the 7th and 8th AJCC staging systems.

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Rectal Gastrointestinal Stromal Tumor (GIST) in the Era of Imatinib: Organ Preservation and Improved Oncologic Outcome

Abstract

Background

Approximately 5% of gastrointestinal stromal tumors (GISTs) originate in the rectum, and historically, radical resection was commonly performed. Little is known about the outcome for rectal GIST in the era of imatinib.

Methods

Using a prospectively maintained database, this study retrospectively analyzed 47 localized primary rectal GISTs treated at our center from 1982 to 2016, stratified by when imatinib became available in 2000. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were analyzed by the Kaplan–Meier method.

Results

Rectal GISTs represented 7.1% of 663 primary GISTs. The findings showed 17 patients in the pre-imatinib era and 30 patients in the imatinib era. The two groups had similar follow-up evaluation, age, gender, Miettinen risk, and distance to the anal verge. In the imatinib era, tumors were smaller at diagnosis (median 4 vs. 5 cm; p = 0.029), and 24 of the 30 patients received perioperative imatinib. In the high-risk patients, organ preservation and negative margins were more common among the 13 patients treated with neoadjuvant imatinib than among the 21 patients treated directly with surgery. High-risk patients who received perioperative imatinib (n = 15) had greater (or nearly significantly greater) 5-year OS, DSS, local RFS, and distant RFS than those who did not (n = 19) (91, 100, 100, and 71% vs. 47, 65, 74, and 41%; p = 0.049, 0.052, 0.077, 0.051, respectively). In the imatinib era, no patient has had a local recurrence or death due to GIST.

Conclusions

The use of imatinib is associated with organ preservation and improved oncologic outcome for patients with rectal GIST.

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Similar Significance of Lymphovascular Invasion with Different Treatment Modalities Among Esophageal Squamous Cell Carcinoma

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The Impact of Sentinel Node-Mapping in Staging High-Risk Endometrial Cancer

Abstract

Background

This study aimed to determine the impact of sentinel lymph node (SLN)-mapping on the staging of high-risk endometrial cancer (endometrioid grade 3, serous, clear cell, carcinosarcoma, deep myometrial invasion, or angiolymphatic invasion).

Methods

The study analyzed a series of 236 patients treated at AC Camargo Cancer Center from June 2007 to February 2017. The compared 75 patients who underwent SLN-mapping (SLN group) with 161 patients who received pelvic ± para-aortic lymphadenectomy (N-SLN group). Patients with adnexal, peritoneal, or suspicious node metastases were excluded from the study.

Results

The groups did not differ in terms of age, histologic type, or presence of deep myometrial invasion. The overall detection rate for SLNs was 85.3%, and bilateral SLNs were observed in 60% of the patients. Of 20 positive SLNs, 8 (40%) were detected only after immunohistochemistry (IHC). The findings showed an overall sensitivity of 90%, a negative predictive value of 95.7%, and a false-negative predictive value of 4.3%. The SLN group had more pelvic node metastases detected than the N-SLN group (26.7 vs 14.3%; p = 0.02). However, the rate of para-aortic node metastases did not differ between the two groups (13.5 vs 5.6%; p = 0.12). Five patients (3.5%) in the N-SLN group had isolated para-aortic node metastases versus none in the patients with SLN mapped. Additionally, the SLN group received more adjuvant chemotherapy (48 vs 33.5%; p = 0.03).

Conclusions

The data suggest that SLN-mapping identifies more pelvic node metastases than lymph node dissection alone and increases the node detection rate by 12.5% after IHC. Furthermore, no isolated para-aortic node metastases are observed when SLN is detected.

http://ift.tt/2xeHF7T

Vitamin Status and the Development of Postoperative Cognitive Decline in Elderly Surgical Oncologic Patients

Abstract

Background

This study aimed to evaluate the influence that serum levels of vitamin B12, folate, and homocysteine have on the development of short-term postoperative cognitive decline in the elderly surgical oncology patient.

Methods

This study was part of a prospective cohort study focused on postoperative cognitive outcomes for patients 65 years of age or older undergoing surgery for a solid malignancy. Postoperative cognitive decline was defined as the change in the combined results of the Ruff Figural Fluency Test and the Trail-Making Test Parts A and B. Patients with the highest change in scores 2 weeks postoperatively compared with baseline were considered to be patients with cognitive decline. Patients with the lowest change were considered to be patients without cognitive decline. To analyze the effect of vitamin levels on the changes in postoperative cognitive scores, uni- and multivariate logistic regression analysis were performed.

Results

The study enrolled 61 patients with and 59 patients without postoperative cognitive decline. Hyperhomocysteinemia was present in 14.2% of the patients. Patients with postoperative cognitive decline more often had hyperhomocysteinemia (27.9 vs 10.2%). Hyperhomocysteinemia was associated with a higher chance for the development of postoperative cognitive decline (odds ratio_adjusted, 11.9; 95% confidence interval, 2.4–59.4). Preoperative vitamin B12 or folate deficiency were not associated with the development of postoperative cognitive decline.

Conclusion

Preoperative hyperhomocysteinemia is associated with the development of postoperative cognitive decline. The presence of preoperative hyperhomocysteinemia could be an indicator for an increased risk of postoperative cognitive decline developing in the elderly.

http://ift.tt/2zFJWKY

Performance Analysis of the American Joint Committee on Cancer 8th Edition Staging System for Retroperitoneal Sarcoma and Development of a New Staging Algorithm for Sarcoma-Specific Survival

Abstract

Background

The American Joint Committee on Cancer (AJCC) recently published the 8th edition of the AJCC Cancer Staging Manual. Major changes were made to the staging algorithm for retroperitoneal sarcoma; however, whether these changes improve staging system performance is questionable.

Methods

This retrospective cohort analysis of 3703 adult patients with retroperitoneal sarcoma in the Surveillance, Epidemiology, and End Results (SEER) database compares a novel staging system incorporating histologic subtype of sarcoma with current and prior AJCC soft tissue sarcoma staging systems using multiple statistical techniques. The effect of tumor size on sarcoma-specific survival was also assessed by flexible, non-linear Cox proportional hazard regression using restricted cubic splines and fractional polynomials.

Results

The relationship between the covariate-adjusted log hazard for disease-specific survival and tumor size is non-linear. Although the new AJCC T classification approximates this hazard fairly well, the overall prognostic impact of tumor size is limited after accounting for other predictive factors. Predictive accuracy and concordance indices of the AJCC 8th edition staging system for retroperitoneal sarcoma are significantly lower than the prior 7th edition. A proposed staging system incorporating histologic grade, tumor size, and histologic subtype is superior to both the AJCC 7th and 8th editions in predicting sarcoma-specific survival.

Conclusion

AJCC committees should not revise tumor staging algorithms unless the changes actually improve the staging system. A proposed staging scheme incorporating data regarding histologic subtype of sarcoma performs significantly better than both the 7th and 8th AJCC staging systems.

http://ift.tt/2xdczgX

Rectal Gastrointestinal Stromal Tumor (GIST) in the Era of Imatinib: Organ Preservation and Improved Oncologic Outcome

Abstract

Background

Approximately 5% of gastrointestinal stromal tumors (GISTs) originate in the rectum, and historically, radical resection was commonly performed. Little is known about the outcome for rectal GIST in the era of imatinib.

Methods

Using a prospectively maintained database, this study retrospectively analyzed 47 localized primary rectal GISTs treated at our center from 1982 to 2016, stratified by when imatinib became available in 2000. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were analyzed by the Kaplan–Meier method.

Results

Rectal GISTs represented 7.1% of 663 primary GISTs. The findings showed 17 patients in the pre-imatinib era and 30 patients in the imatinib era. The two groups had similar follow-up evaluation, age, gender, Miettinen risk, and distance to the anal verge. In the imatinib era, tumors were smaller at diagnosis (median 4 vs. 5 cm; p = 0.029), and 24 of the 30 patients received perioperative imatinib. In the high-risk patients, organ preservation and negative margins were more common among the 13 patients treated with neoadjuvant imatinib than among the 21 patients treated directly with surgery. High-risk patients who received perioperative imatinib (n = 15) had greater (or nearly significantly greater) 5-year OS, DSS, local RFS, and distant RFS than those who did not (n = 19) (91, 100, 100, and 71% vs. 47, 65, 74, and 41%; p = 0.049, 0.052, 0.077, 0.051, respectively). In the imatinib era, no patient has had a local recurrence or death due to GIST.

Conclusions

The use of imatinib is associated with organ preservation and improved oncologic outcome for patients with rectal GIST.

http://ift.tt/2zHSUHA

Similar Significance of Lymphovascular Invasion with Different Treatment Modalities Among Esophageal Squamous Cell Carcinoma

http://ift.tt/2xe9OvE

A qualitative meta-synthesis examining the role of women in African American men's prostate cancer screening and treatment decision-making

Abstract

Objective

Being an African American man is a risk factor for prostate cancer and there is little consensus about the utility of screening, early detection, and the efficacy of treatment for the disease. In this context, this systematic review examines the roles women, particularly wives, play in African American men's prostate cancer screening and treatment decision-making.

Methods

We searched OVID Medline (R), CINAHL (EBSCO), PsychInfo (EBSCO), PubMED, Cochrane Library, ERIC (Firstsearch) and Web of Science to identify peer-review articles published between 1980-2016 that reported qualitative data about prostate cancer screening, diagnosis, or treatment in African American men. We conducted a systematic review of the literature using study appraisal and narrative synthesis.

Results

Following PRISMA guidelines for identifying and screening 1,425 abstracts and papers, we identified ten papers that met our criteria. From our thematic meta-synthesis of the findings from these publications, we found that women played three key roles in African American men's decision-making regarding prostate cancer screening, diagnosis, or treatment: Counselor (i.e., offering advice or information), Coordinator (i.e., promoting healthy behaviors and arranging or facilitating appointments), and Confidant (i.e., providing emotional support and reassurance).

Conclusions

Women are often important confidants to whom men express their struggles, fears and concerns, particularly those related to health, and they help men make appointments, understand medical advice. Better understanding women's supportive roles in promoting positive mental and physical outcomes may be a key to developing effective interventions to improve African American men's decision-making and satisfaction regarding prostate cancer screening and treatment.

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A qualitative meta-synthesis examining the role of women in African American men's prostate cancer screening and treatment decision-making

Abstract

Objective

Being an African American man is a risk factor for prostate cancer and there is little consensus about the utility of screening, early detection, and the efficacy of treatment for the disease. In this context, this systematic review examines the roles women, particularly wives, play in African American men's prostate cancer screening and treatment decision-making.

Methods

We searched OVID Medline (R), CINAHL (EBSCO), PsychInfo (EBSCO), PubMED, Cochrane Library, ERIC (Firstsearch) and Web of Science to identify peer-review articles published between 1980-2016 that reported qualitative data about prostate cancer screening, diagnosis, or treatment in African American men. We conducted a systematic review of the literature using study appraisal and narrative synthesis.

Results

Following PRISMA guidelines for identifying and screening 1,425 abstracts and papers, we identified ten papers that met our criteria. From our thematic meta-synthesis of the findings from these publications, we found that women played three key roles in African American men's decision-making regarding prostate cancer screening, diagnosis, or treatment: Counselor (i.e., offering advice or information), Coordinator (i.e., promoting healthy behaviors and arranging or facilitating appointments), and Confidant (i.e., providing emotional support and reassurance).

Conclusions

Women are often important confidants to whom men express their struggles, fears and concerns, particularly those related to health, and they help men make appointments, understand medical advice. Better understanding women's supportive roles in promoting positive mental and physical outcomes may be a key to developing effective interventions to improve African American men's decision-making and satisfaction regarding prostate cancer screening and treatment.

http://ift.tt/2zt6Cgj

Trends in incidence and associated risk factors of suicide mortality among breast cancer patients

Abstract

Objective

Breast cancer patients are associated with an increased risk for committing suicide. The purpose of this study is to study the trends in the incidence of suicide mortality and identify pertinent risk factors among patients with breast cancer.

Methods

A retrospective examination of the Surveillance Epidemiology and End Results (SEER) database between years 1973 and 2013 was performed.

Results

Overall, 474,128 patients were identified of which 773 had committed suicide. There were no significant differences in the incidence of suicide mortality over the last three decades (1984-1993: 0.14%, 1994-2003: 0.16%, 2004-2013: 0.17%, p=0.173). On logistic regression, younger age (<30 y: OR 6.34, 95% CI: 1.98-20.33, p=0.002, 30-49 y: OR 10.64, 95% CI: 7.97-14.2, p<0.001, 50-69 y: OR 4.7, 95% CI: 3.64-6.07, p<0.001), male sex (OR 4.34, 95% CI: 2.57-7.31, p<0.001), non-white-non-black race (OR 1.39, 95% CI: 1.01-1.91, p=0.046), marital status (single: OR 1.35, 95% CI: 1.04-1.76, p=0.024, separated/divorced/widowed: OR 1.25, 95% CI: 1.01-1.55, p=0.043), undergoing surgery (OR 2.13, 95% CI: 1.23-3.67, p=0.007) and short time elapsed from diagnosis (1^st year: OR 4.67, 95% CI: 3.39-6.42, p<0.001, 2^nd year: OR 2.35, 95% CI: 1.69-3.27, p<0.001) were independent risk factors of suicide mortality.

Conclusions

There have been no identifiable improvements in preventing suicide mortality in the United States. Younger age, male sex, race, marital status and undergoing surgery are independent risk factors for committing suicide, especially in the first year after diagnosis.

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Pelvic re-irradiation using stereotactic ablative radiotherapy (SABR): A systematic review

To perform a systematic review regarding the use of stereotactic ablative radiotherapy (SABR) for the re-irradiation of recurrent malignant disease within the pelvis, to guide the clinical implementation of this technique.

http://ift.tt/2zspsVd

Trends in incidence and associated risk factors of suicide mortality among breast cancer patients

Abstract

Objective

Breast cancer patients are associated with an increased risk for committing suicide. The purpose of this study is to study the trends in the incidence of suicide mortality and identify pertinent risk factors among patients with breast cancer.

Methods

A retrospective examination of the Surveillance Epidemiology and End Results (SEER) database between years 1973 and 2013 was performed.

Results

Overall, 474,128 patients were identified of which 773 had committed suicide. There were no significant differences in the incidence of suicide mortality over the last three decades (1984-1993: 0.14%, 1994-2003: 0.16%, 2004-2013: 0.17%, p=0.173). On logistic regression, younger age (<30 y: OR 6.34, 95% CI: 1.98-20.33, p=0.002, 30-49 y: OR 10.64, 95% CI: 7.97-14.2, p<0.001, 50-69 y: OR 4.7, 95% CI: 3.64-6.07, p<0.001), male sex (OR 4.34, 95% CI: 2.57-7.31, p<0.001), non-white-non-black race (OR 1.39, 95% CI: 1.01-1.91, p=0.046), marital status (single: OR 1.35, 95% CI: 1.04-1.76, p=0.024, separated/divorced/widowed: OR 1.25, 95% CI: 1.01-1.55, p=0.043), undergoing surgery (OR 2.13, 95% CI: 1.23-3.67, p=0.007) and short time elapsed from diagnosis (1^st year: OR 4.67, 95% CI: 3.39-6.42, p<0.001, 2^nd year: OR 2.35, 95% CI: 1.69-3.27, p<0.001) were independent risk factors of suicide mortality.

Conclusions

There have been no identifiable improvements in preventing suicide mortality in the United States. Younger age, male sex, race, marital status and undergoing surgery are independent risk factors for committing suicide, especially in the first year after diagnosis.

http://ift.tt/2l6Ggi6

Erratum to ‘Limitations and opportunities for immune checkpoint inhibitors in pediatric malignancies’ [Cancer Treat. Rev. 58C (2017) 22–33]

Publication date: Available online 21 October 2017
Source:Cancer Treatment Reviews
Author(s): Jeong A Park, Nai-Kong V. Cheung




http://ift.tt/2xWftWG

Validation of Dosimetric Leaf Gap (DLG) prior to its implementation in Treatment Planning System (TPS): TrueBeam™ millennium 120 leaf MLC

Publication date: November–December 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 6
Author(s): Ravindra Shende, Ganesh Patel
AimObjective of present study is to determine optimum value of DLG and its validation prior to being incorporated in TPS for Varian TrueBeam™ millennium 120 leaves MLC.BackgroundPartial transmission through the rounded leaf ends of the Multi Leaf Collimator (MLC) causes a conflict between the edges of the light field and radiation field. Parameter account for this partial transmission is called Dosimetric Leaf Gap (DLG). The complex high precession technique, such as Intensity Modulated Radiation Therapy (IMRT), entails the modeling of optimum value of DLG inside Eclipse Treatment Planning System (TPS) for precise dose calculation.Materials and methodsDistinct synchronized uniformed extension of sweeping dynamic MLC leaf gap fields created by Varian MLC shaper software were use to determine DLG. DLG measurements performed with both 0.13cc semi-flex ionization chamber and 2D-Array I-Matrix were used to validate the DLG; similarly, values of DLG from TPS were estimated from predicted dose. Similar mathematical approaches were employed to determine DLG from delivered and TPS predicted dose. DLG determined from delivered dose measured with both ionization chamber (DLGIon) and I-Matrix (DLGI-Matrix) compared with DLG estimate from TPS predicted dose (DLGTPS). Measurements were carried out for all available 6MV, 10MV, 15MV, 6MVFFF and 10MVFFF beam energies.ResultsMaximum and minimum DLG deviation between measured and TPS calculated DLG was found to be 0.2mm and 0.1mm, respectively. Both of the measured DLGs (DLGIon and DLGI-Matrix) were found to be in a very good agreement with estimated DLG from TPS (DLGTPS).ConclusionsProposed method proved to be helpful in verifying and validating the DLG value prior to its clinical implementation in TPS.



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Sedation After Cardiac Surgery With Propofol or Dexmedetomidine: Between Scylla and Charybdis?

No abstract available

http://ift.tt/2yGrpjC

Descriptive Statistics: Reporting the Answers to the 5 Basic Questions of Who, What, Why, When, Where, and a Sixth, So What?

Descriptive statistics are specific methods basically used to calculate, describe, and summarize collected research data in a logical, meaningful, and efficient way. Descriptive statistics are reported numerically in the manuscript text and/or in its tables, or graphically in its figures. This basic statistical tutorial discusses a series of fundamental concepts about descriptive statistics and their reporting. The mean, median, and mode are 3 measures of the center or central tendency of a set of data. In addition to a measure of its central tendency (mean, median, or mode), another important characteristic of a research data set is its variability or dispersion (ie, spread). In simplest terms, variability is how much the individual recorded scores or observed values differ from one another. The range, standard deviation, and interquartile range are 3 measures of variability or dispersion. The standard deviation is typically reported for a mean, and the interquartile range for a median. Testing for statistical significance, along with calculating the observed treatment effect (or the strength of the association between an exposure and an outcome), and generating a corresponding confidence interval are 3 tools commonly used by researchers (and their collaborating biostatistician or epidemiologist) to validly make inferences and more generalized conclusions from their collected data and descriptive statistics. A number of journals, including Anesthesia & Analgesia, strongly encourage or require the reporting of pertinent confidence intervals. A confidence interval can be calculated for virtually any variable or outcome measure in an experimental, quasi-experimental, or observational research study design. Generally speaking, in a clinical trial, the confidence interval is the range of values within which the true treatment effect in the population likely resides. In an observational study, the confidence interval is the range of values within which the true strength of the association between the exposure and the outcome (eg, the risk ratio or odds ratio) in the population likely resides. There are many possible ways to graphically display or illustrate different types of data. While there is often latitude as to the choice of format, ultimately, the simplest and most comprehensible format is preferred. Common examples include a histogram, bar chart, line chart or line graph, pie chart, scatterplot, and box-and-whisker plot. Valid and reliable descriptive statistics can answer basic yet important questions about a research data set, namely: "Who, What, Why, When, Where, How, How Much?"

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“Houston, We Have a Problem!”: The Role of the Anesthesiologist in the Current Opioid Epidemic

No abstract available

http://ift.tt/2gyjyhs

Chronic Opioid Use After Surgery: Implications for Perioperative Management in the Face of the Opioid Epidemic

Physicians, policymakers, and researchers are increasingly focused on finding ways to decrease opioid use and overdose in the United States both of which have sharply increased over the past decade. While many efforts are focused on the management of chronic pain, the use of opioids in surgical patients presents a particularly challenging problem requiring clinicians to balance 2 competing interests: managing acute pain in the immediate postoperative period and minimizing the risks of persistent opioid use after the surgery. Finding ways to minimize this risk is particularly salient in light of a growing literature suggesting that postsurgical patients are at increased risk for chronic opioid use. The perioperative care team, including surgeons and anesthesiologists, is poised to develop clinical- and systems-based interventions aimed at providing pain relief in the immediate postoperative period while also reducing the risks of opioid use longer term. In this paper, we discuss the consequences of chronic opioid use after surgery and present an analysis of the extent to which surgery has been associated with chronic opioid use. We follow with a discussion of the risk factors that are associated with chronic opioid use after surgery and proceed with an analysis of the extent to which opioid-sparing perioperative interventions (eg, nerve blockade) have been shown to reduce the risk of chronic opioid use after surgery. We then conclude with a discussion of future research directions.

http://ift.tt/2gyBKar

The Opioid Crisis in the United States: Chronic Pain Physicians Are the Answer, Not the Cause

No abstract available

http://ift.tt/2yxgQ2C

Neurosurgical Intensive Care

No abstract available

http://ift.tt/2yGrfJ2

Do Not Resuscitate and the Surgical Patient: Not a Contradiction in Terms

No abstract available

http://ift.tt/2ywbHYF

Opioids for the Treatment of Chronic Pain: Mistakes Made, Lessons Learned, and Future Directions

An overreliance on opioids has impacted all types of pain management, making it undoubtedly a root cause of the "epidemic" of prescription opioid abuse in the United States. Yet, an examination of the statistics that led the US Centers for Disease Control and Prevention to declare that prescription opioid abuse had reached epidemic levels shows that the abuse occurrences and deaths are arising outside the hospital or hospice setting, which strongly implicates the outpatient use of opioids to treat chronic pain. Such abuse and related deaths are occurring in chronic pain patients themselves and also through diversion. Overprescribing to outpatients has afforded distressed and vulnerable individuals access to these highly addictive drugs. The focus of this article is on what we have learned since opioid treatment of chronic pain was first popularized at the end of the 20th century and how this new information can guide chronic pain management in the future.

http://ift.tt/2yHv948

Venovenous Bypass Associated With Acute Kidney Injury Prevention in Liver Transplantation: An Ode to the Retrospective Data Researcher

No abstract available

http://ift.tt/2gyrRtm

Reducing Mortality in Acute Kidney Injury

No abstract available

http://ift.tt/2gyBsjR

The Perioperative Surgical Home Is Not Just a Name

No abstract available

http://ift.tt/2yxgOYy

A Limitation of Intensive Care Unit Sedation Using Volatile Anesthetics

No abstract available

http://ift.tt/2yHv3JO

Tracking Speckles: Overcoming Conventions to Evaluate Right Ventricular Function

No abstract available

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Women and Leadership in Anesthesiology: Can We “Lean In” Further?

No abstract available

http://ift.tt/2gAnIVU

Surveying the Literature: Synopsis of Recent Key Publications

No abstract available

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An Evidence-Based Approach to the Prescription Opioid Epidemic in Orthopedic Surgery

Orthopedic surgery is associated with significant perioperative pain. Providing adequate analgesia is a critical component of patient care and opioids play a vital role in the acute postoperative setting. However, opioid prescribing for patients undergoing orthopedic procedures has recently been identified as a major contributor to the current opioid epidemic. As opioid usage and related morbidity and mortality continue to rise nationwide, opioid-prescribing practices are under increased scrutiny. Here, we update the evidence base and recommendations behind a set of interventions developed at the Hospital for Special Surgery to address the national epidemic at the local level. The main components of our program include (1) guidelines for managing patients who are opioid tolerant and/or have a substance abuse disorder; (2) education programs for patients, emphasizing the role of opioids in recovery after elective orthopedic surgery; (3) education programs for prescribers of controlled substances, including clinical and regulatory aspects; (4) the development of surgery-specific prescribing recommendations for opioid-naive patients; and (5) mechanisms to modify prescribing habits to limit unnecessary prescribing of controlled substances.

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High-Sensitivity Cardiac Troponin T Improves the Diagnosis of Perioperative MI

BACKGROUND: BACKGROUND:The diagnosis of myocardial infarction (MI) after noncardiac surgery has traditionally relied on using relatively insensitive contemporary cardiac troponin (cTn) assays. We hypothesized that using a recently introduced novel high-sensitivity cTnT (hscTnT) assay would increase the detection rate of perioperative MI. METHODS: METHODS:In this ancillary study of the Vitamins in Nitrous Oxide trial, readjudicated incidence rates of myocardial injury (new isolated cTn elevation) and MI were compared when diagnosed by contemporary cTnI versus hscTnT. We probed various relative (eg, >50%) or absolute (eg, +5 ng/L) hscTnT change metrics. Inclusion criteria for this ancillary study were the presence of a baseline and at least 1 postoperative hscTnT value. RESULTS: RESULTS:Among 605 patients, 70 patients (12%) had electrocardiogram changes consistent with myocardial ischemia; 82 patients (14%) had myocardial injury diagnosed by contemporary cTnI, 31 (5.1%) of which had an adjudicated MI. After readjudication, 67 patients (11%) were diagnosed with MI when using hscTnT, a 2-fold increase. Incidence rates of postoperative myocardial injury ranged from 12% (n = 73) to 65% (n = 393) depending on the hscTnT metric used. Incidence rates of MI using various hscTnT change metrics and the presence of ischemic electrocardiogram changes, but without event adjudication, ranged from 3.6% (n = 22) to 12% (n = 74), a >3-fold difference. New postoperative hscTnT elevation, either by absolute or relative hscTnT change metric, was associated with an up to 5-fold increase in 6-month mortality. CONCLUSIONS: CONCLUSIONS:The use of hscTnT compared to contemporary cTnI increases the detection rate of perioperative MI by a factor of 2. Using different absolute or relative hscTnT change metrics may lead to under- or overdiagnosis of perioperative MI.

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Distribution of cancer mortality rates by province in South Africa

Publication date: December 2017
Source:Cancer Epidemiology, Volume 51
Author(s): Felix Made, Kerry Wilson, Ruxana Jina, Nonhlanhla Tlotleng, Samantha Jack, Vusi Ntlebi, Tahira Kootbodien
IntroductionCancer mortality rates are expected to increase in developing countries. Cancer mortality rates by province remain largely unreported in South Africa. This study described the 2014 age standardised cancer mortality rates by province in South Africa, to provide insight for strategic interventions and advocacy.Methods2014 deaths data were retrieved from Statistics South Africa. Deaths from cancer were extracted using 10th International Classification of Diseases (ICD) codes for cancer (C00-C97). Adjusted 2013 mid-year population estimates were used as a standard population. All rates were calculated per 100 000 individuals.ResultsNearly 38 000 (8%) of the total deaths in South Africa in 2014 were attributed to cancer. Western Cape Province had the highest age standardised cancer mortality rate in South Africa (118, 95% CI: 115–121 deaths per 100 000 individuals), followed by the Northern Cape (113, 95% CI: 107–119 per 100 000 individuals), with the lowest rate in Limpopo Province (47, 95% CI: 45–49 per 100 000). The age standardised cancer mortality rate for men (71, 95% CI: 70–72 per 100 000 individuals) was similar to women (69, 95% CI: 68–70 per 100 000). Lung cancer was a major driver of cancer death in men (13, 95% CI: 12.6–13.4 per 100 000). In women, cervical cancer was the leading cause of cancer death (13, 95% CI: 12.6–13.4 per 100 000 individuals).ConclusionThere is a need to further investigate the factors related to the differences in cancer mortality by province in South Africa. Raising awareness of risk factors and screening for cancer in the population along with improved access and quality of health care are also important.



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Risk of cardiovascular disease among women with endometrial cancer compared to cancer-free women in the Women’s Health Initiative

Publication date: December 2017
Source:Cancer Epidemiology, Volume 51
Author(s): Ashley S. Felix, Amy Lehman, Randi E. Foraker, Michelle J. Naughton, Julie K. Bower, Lewis Kuller, Gloria E. Sarto, Marcia L. Stefanick, Linda Van Horn, Rebecca D. Jackson, Electra D. Paskett
BackgroundThe majority of women diagnosed with endometrial cancer (EC) have low cancer-specific mortality; however, a high prevalence of cardiovascular disease (CVD) risk factors places EC patients at high risk of developing CVD. In the Women's Health Initiative (WHI), we assessed the hypothesis that CVD risk was higher among women who developed EC compared with women who did not develop EC.MethodsWe compared the incidence of fatal and non-fatal CVD events among 1,179 women who developed Type I EC, 211 women who developed Type II EC, and 92,217 women who did not develop EC. We first estimated univariable cause-specific hazard ratios (CHRs) and 95% confidence intervals (CIs) for the association between an EC diagnosis (overall and by EC type) with CVD risk using Cox proportional hazards regression. Potential confounders were examined using a risk factor modeling approach; final multivariable-adjusted models included covariates that changed univariable CHRs for EC diagnosis by≥5%.ResultsIn multivariable-adjusted models, CVD risk did not significantly differ between women who developed EC compared to women who did not develop EC (CHR=1.01, 95% CI=0.87–1.16), particularly for the subgroup of women who developed Type I EC (CHR=0.98, 95% CI=0.84–1.14); however, there was a positive but statistically nonsignificant association for Type II EC (CHR=1.32, 95% CI=0.88–1.97).ConclusionDespite our null findings, women with EC should still receive counseling and support to make lifestyle changes aimed at reducing weight as appropriate, given the high prevalence of CVD risk factors at diagnosis.



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Distribution of cancer mortality rates by province in South Africa

Publication date: December 2017
Source:Cancer Epidemiology, Volume 51
Author(s): Felix Made, Kerry Wilson, Ruxana Jina, Nonhlanhla Tlotleng, Samantha Jack, Vusi Ntlebi, Tahira Kootbodien
IntroductionCancer mortality rates are expected to increase in developing countries. Cancer mortality rates by province remain largely unreported in South Africa. This study described the 2014 age standardised cancer mortality rates by province in South Africa, to provide insight for strategic interventions and advocacy.Methods2014 deaths data were retrieved from Statistics South Africa. Deaths from cancer were extracted using 10th International Classification of Diseases (ICD) codes for cancer (C00-C97). Adjusted 2013 mid-year population estimates were used as a standard population. All rates were calculated per 100 000 individuals.ResultsNearly 38 000 (8%) of the total deaths in South Africa in 2014 were attributed to cancer. Western Cape Province had the highest age standardised cancer mortality rate in South Africa (118, 95% CI: 115–121 deaths per 100 000 individuals), followed by the Northern Cape (113, 95% CI: 107–119 per 100 000 individuals), with the lowest rate in Limpopo Province (47, 95% CI: 45–49 per 100 000). The age standardised cancer mortality rate for men (71, 95% CI: 70–72 per 100 000 individuals) was similar to women (69, 95% CI: 68–70 per 100 000). Lung cancer was a major driver of cancer death in men (13, 95% CI: 12.6–13.4 per 100 000). In women, cervical cancer was the leading cause of cancer death (13, 95% CI: 12.6–13.4 per 100 000 individuals).ConclusionThere is a need to further investigate the factors related to the differences in cancer mortality by province in South Africa. Raising awareness of risk factors and screening for cancer in the population along with improved access and quality of health care are also important.



http://ift.tt/2zsuO2x

Risk of cardiovascular disease among women with endometrial cancer compared to cancer-free women in the Women’s Health Initiative

Publication date: December 2017
Source:Cancer Epidemiology, Volume 51
Author(s): Ashley S. Felix, Amy Lehman, Randi E. Foraker, Michelle J. Naughton, Julie K. Bower, Lewis Kuller, Gloria E. Sarto, Marcia L. Stefanick, Linda Van Horn, Rebecca D. Jackson, Electra D. Paskett
BackgroundThe majority of women diagnosed with endometrial cancer (EC) have low cancer-specific mortality; however, a high prevalence of cardiovascular disease (CVD) risk factors places EC patients at high risk of developing CVD. In the Women's Health Initiative (WHI), we assessed the hypothesis that CVD risk was higher among women who developed EC compared with women who did not develop EC.MethodsWe compared the incidence of fatal and non-fatal CVD events among 1,179 women who developed Type I EC, 211 women who developed Type II EC, and 92,217 women who did not develop EC. We first estimated univariable cause-specific hazard ratios (CHRs) and 95% confidence intervals (CIs) for the association between an EC diagnosis (overall and by EC type) with CVD risk using Cox proportional hazards regression. Potential confounders were examined using a risk factor modeling approach; final multivariable-adjusted models included covariates that changed univariable CHRs for EC diagnosis by≥5%.ResultsIn multivariable-adjusted models, CVD risk did not significantly differ between women who developed EC compared to women who did not develop EC (CHR=1.01, 95% CI=0.87–1.16), particularly for the subgroup of women who developed Type I EC (CHR=0.98, 95% CI=0.84–1.14); however, there was a positive but statistically nonsignificant association for Type II EC (CHR=1.32, 95% CI=0.88–1.97).ConclusionDespite our null findings, women with EC should still receive counseling and support to make lifestyle changes aimed at reducing weight as appropriate, given the high prevalence of CVD risk factors at diagnosis.



http://ift.tt/2xVardi

Nodal areas of potential geographic error in adjuvant radiotherapy for biliary tract cancer

To determine the areas of potential geographic error in adjuvant radiotherapy (RT) for biliary-tract cancer (BTC) by comparing pathological-surgical data on the pattern of nodal spread with the extent of elective nodal CTV used in published RT studies in this setting.

http://ift.tt/2yyy6oi

Multi-criterial patient positioning based on dose recalculation on scatter-corrected CBCT images

Our aim was to evaluate the feasibility and potential advantages of dose guided patient positioning based on dose recalculation on scatter corrected cone beam computed tomography (CBCT) image data.

http://ift.tt/2l59u0L

Exploratory Study of Impact of Cancer-Related Posttraumatic Stress Symptoms on Diabetes Self-Management among Cancer Survivors

Abstract

Objective

Posttraumatic stress symptoms (PTSS) can be triggered by a diagnosis of a potentially life-threatening illness such as cancer. Little is known about the impact of cancer-related PTSS symptoms on self-management behaviors for comorbid chronic medical conditions such as diabetes mellitus (DM).

Methods

We recruited patients with DM and a recent diagnosis of early-stage cancer from two medical centers in New York City. Cancer-related PTSS were assessed using the Impact of Events scale (IES, score ≥26). DM self-management behaviors (medication adherence, exercise, healthy diet, and glucose testing) were measured 3 months later. Logistic regression was used to assess the association between cancer-related PTSS symptoms and DM self-management behaviors, adjusting for gender, marital status, and anxiety symptoms.

Results

Of 56 participants recruited, 33% reported cancer-related PTSS symptoms. Elevated cancer-related PTSS symptoms were associated with lack of healthy diet (Odds Ratio [OR]: 0.08, 95% confidence interval [CI]: 0.01-0.62).

Conclusions

Early-stage cancer survivors with cancer-related PTSS symptoms were less likely to adhere to some DM self-management behaviors. Providers should recognize the impact of cancer-related PTSS symptoms to better support comorbid disease management in cancer survivors.

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Exploratory Study of Impact of Cancer-Related Posttraumatic Stress Symptoms on Diabetes Self-Management among Cancer Survivors

Abstract

Objective

Posttraumatic stress symptoms (PTSS) can be triggered by a diagnosis of a potentially life-threatening illness such as cancer. Little is known about the impact of cancer-related PTSS symptoms on self-management behaviors for comorbid chronic medical conditions such as diabetes mellitus (DM).

Methods

We recruited patients with DM and a recent diagnosis of early-stage cancer from two medical centers in New York City. Cancer-related PTSS were assessed using the Impact of Events scale (IES, score ≥26). DM self-management behaviors (medication adherence, exercise, healthy diet, and glucose testing) were measured 3 months later. Logistic regression was used to assess the association between cancer-related PTSS symptoms and DM self-management behaviors, adjusting for gender, marital status, and anxiety symptoms.

Results

Of 56 participants recruited, 33% reported cancer-related PTSS symptoms. Elevated cancer-related PTSS symptoms were associated with lack of healthy diet (Odds Ratio [OR]: 0.08, 95% confidence interval [CI]: 0.01-0.62).

Conclusions

Early-stage cancer survivors with cancer-related PTSS symptoms were less likely to adhere to some DM self-management behaviors. Providers should recognize the impact of cancer-related PTSS symptoms to better support comorbid disease management in cancer survivors.

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Exploiting poly(I:C) to induce cancer cell apoptosis

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Exploiting poly(I:C) to induce cancer cell apoptosis

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The involvement of lncRNAs in the development and progression of pancreatic cancer.

Related Articles

The involvement of lncRNAs in the development and progression of pancreatic cancer.

Cancer Biol Ther. 2017 Oct 20;:0

Authors: Duguang L, Jin H, Xiaowei Q, Peng X, Xiaodong W, Zhennan L, Jianjun Q, Jie Y

Abstract
Pancreatic cancer is one of the most malignant tumors that are difficult to diagnose at its early stage and there is no effective therapy. Recent studies uncovered that many non-protein-coding RNAs including the class of long noncoding RNAs (lncRNAs) are differentially expressed in various types of tumors and they are potent regulators of tumor progression and metastasis. LncRNA can mediate tumor initiation, proliferation, migration and metastasis through modulating epigenetic modification, alternative splicing, transcription, and protein translation. In this review, we discuss the molecular mechanism of lncRNAs in the involvement of tumor growth, survival, epithelial-mesenchymal transition, tumor microenvironment, cancer stem cells and chemoresistance in pancreatic ductal adenocarcinoma (PDAC).

PMID: 29053398 [PubMed - as supplied by publisher]

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Embryonic Stem Cell Secreted Factors Decrease Invasiveness of Triple-Negative Breast Cancer Cells Through Regulome Modulation.

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Embryonic Stem Cell Secreted Factors Decrease Invasiveness of Triple-Negative Breast Cancer Cells Through Regulome Modulation.

Cancer Biol Ther. 2017 Oct 20;:0

Authors: Tarasewicz E, Oakes RS, Aviles MO, Straehla J, Chilton KM, Decker JT, Wu J, Shea LD, Jeruss JS

Abstract
Stem cell microenvironments decrease the invasiveness of cancer cells, and elucidating the mechanisms associated with disease regression could further the development of targeted therapies for aggressive cancer subtypes. To this end, we applied an emerging technology, TRanscriptional Activity CEll aRray (TRACER), to investigate the reprogramming of triple-negative breast cancer (TNBC) cells in conditions that promoted a less aggressive phenotype. The repressive environment was established through exposure to mouse embryonic stem cell conditioned media (mESC CM). Assessment of carcinogenic phenotypes indicated that mESC CM exposure decreased proliferation, invasion, migration, and stemness in TNBC cells. Protein expression analysis revealed that mESC CM exposure increased expression of the epithelial protein E-cadherin and decreased the mesenchymal protein MMP9. Gene expression analysis showed that mESC CM decreased epithelial to mesenchymal transition (EMT) markers fibronectin, vimentin, and Snail. Over a period of 6 days, TRACER quantified changes in activity of 11 transcription factors (TFs) associated with oncogenic progression. The EMT profile was decreased in association with the activity of 7 TFs (Smad3, NF-κΒ, MEF2, GATA, Hif1, Sp1, and RXR). Further examination of Smad3 and GATA expression and phosphorylation revealed that mESC CM exposure decreased noncanonical Smad3 phosphorylation and Smad3-mediated gene expression, increased GATA3 expression and phosphorylation, and resulted in a synergistic decrease in migration of GATA3 overexpressing MDA-MB-231 cells. Collectively, the application of TRACER to examine TF activity associated with the transition of cancer cells to a less aggressive phenotype, as directed by mESC CM, identified novel mechanistic events linking the embryonic microenvironment to both favorable changes and cellular plasticity in TNBC cell phenotypes.

PMID: 29053396 [PubMed - as supplied by publisher]

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Overexpression of HN1L promotes cell malignant proliferation in non-small cell lung cancer.

Related Articles

Overexpression of HN1L promotes cell malignant proliferation in non-small cell lung cancer.

Cancer Biol Ther. 2017 Oct 20;:0

Authors: Li L, Zeng TT, Zhang BZ, Li Y, Zhu YH, Guan XY

Abstract
Non-small cell lung cancer (NSCLC) is a progressive malignant disease, involving the activation of oncogenes and inactivation of tumor suppressors. In this study, we identified and characterized a novel oncogene hematopoietic- and neurologic-expressed sequence 1-like (HN1L) in human NSCLC. Overexpression of HN1L was frequently detected in primary NSCLC compared with their non-tumor counterparts (P < 0.001), which was significantly associated with tumor size (P = 0.022). In addition, Kaplan-Meier analysis showed that upregulation of HN1L correlated with worse overall survival (P = 0.029) and disease-free survival (P = 0.011) for NSCLC patients. Both in vitro and in vivo studies demonstrated that inhibition of HN1L expression with shRNA dramatically inhibited cell growth, adherent and non-adherent colony formation, and tumorigenicity in nude mice. The positive correlation of HN1L expression and Ki67 level in a large NSCLC samples further suggested the key role of HN1L in the regulation of cell growth. Further study showed that knockdown of HN1L resulted in dramatic cell cycle arrest by interfering with MAPK pathway via interacting with RASA4 protein. In conclusion, HN1L plays a crucial role in the progression of NSCLC by contributing to malignant proliferation, with possible use as a new intervention point for therapeutic strategies.

PMID: 29053395 [PubMed - as supplied by publisher]

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Some chemotherapeutics-treated colon cancer cells display a specific phenotype being a combination of stem-like and senescent cell features.

Related Articles

Some chemotherapeutics-treated colon cancer cells display a specific phenotype being a combination of stem-like and senescent cell features.

Cancer Biol Ther. 2017 Oct 20;:0

Authors: Was H, Czarnecka J, Kowalczyk A, Barszcz K, Bernas T, Piwocka K, Kaminska B

Abstract
Colorectal cancer (CRC) is the second leading cause of death among cancer patients in the Northern countries. CRC can reappear a long time after treatment. Recent clinical studies demonstrated that, in response to chemotherapy, cancer cells may undergo stress-induced premature senescence (SIPS), which typically results in growth arrest. Nonetheless, these senescent cells were reported to divide in an atypical manner and thus contribute to cancer re-growth. Therefore, we examined if SIPS escape may follow treatment with chemotherapeutics used clinically: 5-fluorouracil (5-FU), oxaliplatin (OXA) and irinotecan (IRINO). To mimic the therapeutic regimes we exposed human colon cancer HCT116 and SW480 cells to repeated cycles of drug treatment. The cells treated with 5-FU or IRINO exhibited several hallmarks of SIPS: growth arrest, increased size and granularity, polyploidization, augmented activity of the SA-β-galactosidase, accumulation of P21 and CYCLIN D1 proteins, and the senescence-associated secretory phenotype. Moreover, re-population of the cancer cell cultures was delayed upon treatment with the senescence-inducing agents. At the same time, we detected a subpopulation of senescent colon cancer cells with features of stemness: elevated NANOG expression, exclusion of Hoechst 33342 (typical for side population) and increased CD24 expression. Additionally, rare, polyploid cells exhibited blastocyst-like morphology and produced progeny. In parallel, majority of chemotherapeutics-treated cells underwent mesenchymal to epithelial transition, as the percentage of CD44-positve cells was reduced, and levels of E-cadherin (epithelial marker) were elevated. Our study demonstrates that a subpopulation of chemotherapeutics-treated colon cancer cells display a specific phenotype being a combination of stem-like and senescent cell features. This may contribute to their resistance to chemotherapy and their ability to re-grow cancer after completion of therapeutic intervention.

PMID: 29053388 [PubMed - as supplied by publisher]

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Cancers, Vol. 9, Pages 139: CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth

Cancers, Vol. 9, Pages 139: CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth

Cancers doi: 10.3390/cancers9100139

Authors: Vita Golubovskaya Robert Berahovich Hua Zhou Shirley Xu Hizkia Harto Le Li Cheng-Chi Chao Mike Ming Mao Lijun Wu

CD47 is a glycoprotein of the immunoglobulin superfamily that is often overexpressed in different types of hematological and solid cancer tumors and plays important role in blocking phagocytosis, increased tumor survival, metastasis and angiogenesis. In the present report, we designed CAR (chimeric antigen receptor)-T cells that bind CD47 antigen. We used ScFv (single chain variable fragment) from mouse CD47 antibody to generate CD47-CAR-T cells for targeting different cancer cell lines. CD47-CAR-T cells effectively killed ovarian, pancreatic and other cancer cells and produced high level of cytokines that correlated with expression of CD47 antigen. In addition, CD47-CAR-T cells significantly blocked BxPC3 pancreatic xenograft tumor growth after intratumoral injection into NSG mice. Moreover, we humanized mouse CD47 ScFv and showed that it effectively bound CD47 antigen. The humanized CD47-CAR-T cells also specifically killed ovarian, pancreatic, and cervical cancer cell lines and produced IL-2 that correlated with expression of CD47. Thus, CD47-CAR-T cells can be used as a novel cellular therapeutic agent for treating different types of cancer.

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Adolescent obesity and adult male breast cancer in a cohort of 1,382,093 men

Abstract

Male breast cancer (MBC) accounts for 1% of all breast cancer. Adult obesity and tallness are risk factors for MBC, but the role of adolescent fatness is largely unknown. We aimed to assess the association between body mass index (BMI) in adolescence and the incidence of MBC in a large cohort of 16-19 year-old Israeli males.

1,382,093 Jewish Israeli males aged 16-19 who underwent anthropometric measurements, a General Intelligence Test (GIT) and other examinations during 1967-2011, were followed up to 31.12.2012 for MBC incidence. Cox proportional hazards models assessed the association between adolescent BMI (as WHO BMI categories and as age-specific CDC percentiles) and time to MBC diagnosis, adjusting for sociodemographic covariates.

Of 100 MBC cases diagnosed during 29,386,233 person-years of follow-up, 97 were included in multivariable analyses. Compared to 'healthy' BMI (18.5-24.9kg/m²) and adjusted for year of birth, country of origin and GIT score, higher adolescent BMI was associated with higher MBC risk: hazard ratio (HR)=2.01 (95% confidence interval [CI]1.14-3.55, p=0.015) in overweight (25.0≤BMI<30.0kg/m²) adolescents; and HR=4.97 (95%CI 2.14-11.53, p=0.0002) in obese (BMI≥30.0kg/m²) adolescents. When CDC age-specific BMI percentiles were assessed results were similar and statistically significant for obesity. Additionally, low (vs. high) GIT score (HR=4.76, 95%CI 1.96-12.50, p=0.001) and European (vs. west-Asian) origin (HR=1.99, 95%CI 1.19-3.34, p=0.009) were independent predictors of MBC.

Measured adolescent overweight and obesity are associated with increased risk of MBC, suggesting a modifiable risk factor potentially allowing for early intervention. The novel association with cognitive function should be further explored. This article is protected by copyright. All rights reserved.

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Comparative Efficacy and Tolerability of Antiemetic Prophylaxis for Adult Highly Emetogenic Chemotherapy: A Network Meta-analysis of 143 Randomized Controlled Trials

Abstract

Chemotherapy-induced nausea and vomiting (CINV) is one of the commonest side-effects among cancer patients. However, there is lacking of hierarchical evidences comparing different antiemetics against highly emetogenic chemotherapy. Therefore, we conducted a network meta-analysis to investigate their comparative efficacy and tolerability. Randomized controlled trials that compared different antiemetic categories for adult highly emetogenic chemotherapy were included after searching PubMed, Web of Science, Embase and Cochrane Central. Acute-phase no emesis and no nausea were identified as primary endpoints. We made pairwise and hierarchical calculations by random-effects model. Effect sizes were presented by odds ratio and 95% confidential interval. Subgroup analysis was additionally performed. 143 randomized trials were included into pooled analysis, containing 22776 patients and 18 antiemetic categories. 5-HT₃ RA plus corticosteroid plus NK-1 RA plus other (5CNO) displayed best protection against both acute emesis (SUCRA: 99.7%) and nausea (95.6%). 5CNO (99.7%) and 5-HT₃ RA plus corticosteroid plus other (5CO, 85.3%) topped subgroup hierarchies for no-naivety and anthracycline plus cyclophosphamide (AC)-based studies. On the other hand, 5-HT₃ RA plus dopamine RA plus other (5DO) may be best fit for delayed emesis (92.0%) and nausea (92.7%). Subgroups featuring no-naivety and AC-based trials preferred 5DO (91.9%) and 5CN (88.6%) respectively. In addition, dopamine RA plus other (DO) had the lowest incidence of TRAE in most circumstances, except for AC-based subgroup where corticosteroid plus dopamine RA plus other (CDO) preponderated (69.2%). 5CNO and 5DO should be considered as first-line regimens against highly emetogenic chemotherapy induced acute and delayed CINV respectively. This article is protected by copyright. All rights reserved.

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Malaria, Epstein-Barr virus, vitamin A, and Burkitt's lymphoma: Response to Joob and Wiwanitkit

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Anti-glypican-1 antibody-drug conjugate exhibits potent preclinical antitumor activity against glypican-1 positive uterine cervical cancer

Abstract

Glypican-1 (GPC1) is highly expressed in solid tumors, especially squamous cell carcinomas (SCCs), and is thought to be associated with disease progression. We explored the use of a GPC1-targeted antibody-drug conjugate (ADC) as a novel treatment for uterine cervical cancer. On immunohistochemical staining, high expression levels of GPC1 were detected in about 50% of uterine cervical cancer tissues and also in a tumor that had relapsed after chemoradiotherapy. Novel anti-GPC1 monoclonal antibodies were developed, and clone 01a033 was selected as the best antibody for targeted delivery of the cytotoxic agent monomethyl auristatin F (MMAF) into GPC1-positive cells. The anti-GPC1 antibody was conjugated with MMAF. On flow cytometry, HeLa and ME180 cervical cancer cells highly expressed GPC1, however, RMG-I ovarian clear cell cancer cell line showed weak expression. The GPC1-ADC was rapidly internalized into GPC1-expressing cells in vitro and was potently cytotoxic to cancer cells highly expressing GPC1. There were no inhibitory effects on cancer cells with low expression of GPC1. In a murine xenograft model, GPC1-ADC also had significant and potent tumor growth inhibition. GPC1-ADC–mediated G2/M phase cell cycle arrest was detected, indicating that the dominant antitumor effect in vivo was MMAF-mediated. The toxicity of GPC-ADC was tolerable within the therapeutic dose range in mice. Our data showed that GPC1-ADC has potential as a promising therapy for uterine cervical cancer. This article is protected by copyright. All rights reserved.

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Cancer incidence in adults living in the vicinity of nuclear power plants in France, based on data from the French Network of Cancer Registries

Abstract

Nuclear power plants (NPPs) release toxic emissions into the environment that may affect neighboring populations. This ecologic study was designed to investigate the possibility of an excess incidence of cancer in the vicinity of French NPPs by examining the incidence by municipality of 12 types of cancer in the population aged 15 years and older during the 1995-2011 period. Population exposure to pollution was estimated on the basis of distance from towns of residence to the NPP. Using regression models, we assessed the risk of cancer in a 20-kilometer zone around NPPs and observed an excess incidence of bladder cancer (Relative Risk (RR), 95% Credibility Interval (95% CI)) in men and women (RR_men = 1.08; 95% CI: 1.00, 1.17 and RR_women = 1.19; 95% CI: 1.02, 1.39). Women living within the 20-km proximity areas had a significantly reduced risk of thyroid cancer (RR_women = 0.86; 95% CI: 0.77, 0.96). No excess risk of hematologic malignancies in either sex was seen. The higher than expected incidence of bladder cancer may be due to an excess incidence localized around the Flamanville NPP and the nearby La Hague nuclear waste treatment center, which is a source of chemical contaminants, many (including arsenic) of them known risk factors for bladder cancer. Differences in medical practices could explain the reduced risk of thyroid cancer. In this first study of adults living near NPPs in France, cancer incidence is significantly higher than in the references populations for one of the cancer types studied: bladder cancer. This article is protected by copyright. All rights reserved.

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Malaria, Epstein-Barr virus, vitamin A and Burkitt's lymphoma

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Targeting Class I Histone Deacetylases by the Novel Small Molecule Inhibitor 4SC-202 Blocks Oncogenic Hedgehog-GLI Signaling and Overcomes Smoothened Inhibitor Resistance

Abstract

Aberrant activation of Hedgehog (HH)/GLI signaling is causally involved in numerous human malignancies, including basal cell carcinoma (BCC) and medulloblastoma. HH pathway antagonists targeting Smoothened (SMO), an essential effector of canonical HH/GLI signaling, show significant clinical success in BCC patients and have recently been approved for the treatment of advanced and metastatic BCC. However, rapid and frequent development of drug resistance to SMO inhibitors (SMOi) together with severe side effects caused by prolonged SMOi treatment call for alternative treatment strategies targeting HH/GLI signaling downstream of SMO. In the present study, we report that 4SC-202, a novel clinically validated inhibitor of class I histone deacetylases (HDACs), efficiently blocks HH/GLI signaling. Notably, 4SC-202 treatment abrogates GLI activation and HH target gene expression in both SMOi-sensitive and resistant cells. Mechanistically, we propose that the inhibition of HDACs 1/2/3 is crucial for targeting oncogenic HH/GLI signaling, and that class I HDAC inhibitors either in combination with SMOi or as second line therapy may improve the treatment options for HH-associated malignancies with SMOi resistance. This article is protected by copyright. All rights reserved.

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Lifetime alcohol intake and risk of non-Hodgkin lymphoma: Findings from the Melbourne Collaborative Cohort Study

Abstract

Cohort studies have reported inconsistent evidence regarding alcohol intake and risk of non-Hodgkin lymphoma (NHL), mostly based on alcohol intake assessed close to study enrolment. We examined this association using alcohol intake measured from age 20 onwards. We calculated usual alcohol intake for 10-year periods from age 20 using recalled frequency and quantity of beverage-specific consumption for 37,990 participants aged 40-69 years from the Melbourne Collaborative Cohort Study. Cox regression was performed to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between alcohol intake (g/day) and NHL risk. After a mean follow-up of 19.3 years, 538 NHL cases were diagnosed. Approximately 80% of participants were either lifetime abstainers or consumed below 20 g of ethanol/day. All categories of lifetime alcohol intake were associated with about 20% lower incidence of NHL compared with lifetime abstention, but there was no evidence of a trend by amount consumed (HR = 0.97 per 10 g/day increment in intake, 95% CI: 0.92-1.03; p value=0.3). HRs for beer, wine and spirits were 0.91 (95% CI: 0.83-1.00; p value=0.05), 1.03 (95% CI: 0.94-1.12; p value=0.6) and 1.06 (95% CI: 0.83-1.37; p value=0.6), respectively, per 10 g/day increment in lifetime intake. There were no significant differences in associations between NHL subtypes. In this low-drinking cohort, we did not detect a dose-dependent association between lifetime alcohol intake and NHL risk. This article is protected by copyright. All rights reserved.

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The joint effects of major lifestyle factors on colorectal cancer risk among Chinese men: A prospective cohort study

Abstract

Previous studies have suggested individual healthy lifestyle factors are related to lower risk of colorectal cancer. Their joint effects, however, have rarely been investigated. We aimed to assess the combined lifestyle impact on colorectal cancer risk and to estimate the population attributable risks of these lifestyle factors. Using data from the Shanghai Men's Health Study (2002-2013), we constructed healthy lifestyle index composing the following lifestyle factors: smoking, alcohol consumption, diet, waist-hip ratio and exercise participation. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Over a median of 9.28 years' follow-up, 671 colorectal cancer cases occurred (400 colon cancer and 274 rectal cancer) among 59503 men. Each increment of healthy lifestyle index was associated with a 17% lower risk of colorectal cancer (HR=0.83, 95%CI: 0.78, 0.89), 10% of colon cancer (HR=0.90, 95%CI: 0.83, 0.99) and 27% of rectal cancer (HR=0.73, 95%CI: 0.66, 0.82). If all men in the cohort followed a lifestyle as defined by these five factors, 21% colorectal cancer cases would have been prevented (PAR=21%, 95%CI: 4%, 36%). In conclusion, combined lifestyle factors are significantly related to lower risk of colorectal cancer and the effects are more pronounced on rectal cancer than on colon cancer. This article is protected by copyright. All rights reserved.

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Impact of gender-neutral or girls-only vaccination against human papillomavirus – Results of a community-randomized clinical trial (I)

Abstract

Human papillomavirus (HPV) vaccine is efficacious but the real-life effectiveness of gender-neutral and girls-only vaccination strategies is unknown. We report a community-randomized trial on the protective effectiveness [(PE) = vaccine efficacy (VE) + herd effect (HE)] of the two strategies among females in virtually HPV vaccination naïve population. We randomized 33 Finnish communities into Arm A) gender-neutral vaccination with AS04-adjuvanted HPV16/18 vaccine (11 communities), Arm B) HPV vaccination of girls and hepatitis B-virus (HBV) vaccination of boys (11 communities) or Arm C) gender-neutral HBV vaccination (11 communities). All resident 39,420 females and 40,852 males born 1992-95 were invited in 2007-09. Virtually all (99%) 12- to 15-year-old participating males (11,662) and females (20,513) received three doses resulting in uniform 20-30% male and 50% female vaccination coverage by birth cohort. Four years later (2010-14) 11,396 cervicovaginal samples obtained from 18.5 year-old women were tested for HPV DNA, and prevalence of cervical HPV infections by trial arm and birth cohort was the main outcome measure. VEs against HPV16/18 varied between 89.2% and 95.2% across birth cohorts in arms A and B. The VEs against non-vaccine types consistent with cross-protection were highest in those born 1994-95 for HPV45 (VE_A 82.8%; VE_B 86.1%) and for HPV31 (VE_A 77.6%, VE_B 84.6%). The HEs in the non HPV-vaccinated were statistically significant in those born 1994-95 for HPV18 (HE_A 51.0%; 95%CI 8.3-73.8, HE_B 47.2%; 6.5-70.2) and for HPV31/33 in arm A (HE_A 53.7%; 22.1-72.5). For HPV16 and 45 no significant herd effects were detected. PE estimates against HPV16/18 were similar by both strategies (PE_A 58.1%; 45.1-69.4; PE_B 55.7%; 42.9-66.6). PE estimates against HPV31/33 were higher by the gender-neutral vaccination (PE_A 60.5%; 43.6-73.4; PE_B 44.5%; 24.9-60.6). In conclusion, while gender-neutral strategy enhanced the effectiveness of HPV vaccination for cross-protected HPV types with low to moderate coverage, high coverage in males appears to be key to providing a substantial public health benefit also to unvaccinated females. Trial registration http://ift.tt/2gyZfQI NCT000534638 This article is protected by copyright. All rights reserved.

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Species-specific role of gene-adjacent retroelements in human and mouse gastric carcinogenesis

Abstract

Helicobacter pylori (HP) infection promotes the recruitment of bone marrow stem cells into chronic gastritis lesions. Some of these marrow stem cells can differentiate into gastric epithelial cells and neoplastic cells. We propose that HP-associated methylation could stabilize trans-differentiation of marrow-derived stem cells and that an unstable methylation status is associated with a risk of gastric cancer. Pathobiologic behavior of experimental mouse gastric cancer is mild compared to invasive and metastatic human gastric cancer. Differences in epigenetic stabilization of adult cell phenotypes between humans and mice could provide a foundation to explore the development of invasive and metastatic gastric cancer. Retroelements are highly repetitive sequences that play an essential role in the generation of species diversity. In this review, we analyzed retroelements adjacent to human and mouse housekeeping genes and proposed a possible epigenetic mechanism for HP-associated carcinogenesis. This article is protected by copyright. All rights reserved.

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Cancers, Vol. 9, Pages 139: CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth

Cancers, Vol. 9, Pages 139: CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth

Cancers doi: 10.3390/cancers9100139

Authors: Vita Golubovskaya Robert Berahovich Hua Zhou Shirley Xu Hizkia Harto Le Li Cheng-Chi Chao Mike Ming Mao Lijun Wu

CD47 is a glycoprotein of the immunoglobulin superfamily that is often overexpressed in different types of hematological and solid cancer tumors and plays important role in blocking phagocytosis, increased tumor survival, metastasis and angiogenesis. In the present report, we designed CAR (chimeric antigen receptor)-T cells that bind CD47 antigen. We used ScFv (single chain variable fragment) from mouse CD47 antibody to generate CD47-CAR-T cells for targeting different cancer cell lines. CD47-CAR-T cells effectively killed ovarian, pancreatic and other cancer cells and produced high level of cytokines that correlated with expression of CD47 antigen. In addition, CD47-CAR-T cells significantly blocked BxPC3 pancreatic xenograft tumor growth after intratumoral injection into NSG mice. Moreover, we humanized mouse CD47 ScFv and showed that it effectively bound CD47 antigen. The humanized CD47-CAR-T cells also specifically killed ovarian, pancreatic, and cervical cancer cell lines and produced IL-2 that correlated with expression of CD47. Thus, CD47-CAR-T cells can be used as a novel cellular therapeutic agent for treating different types of cancer.

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Adolescent obesity and adult male breast cancer in a cohort of 1,382,093 men

Abstract

Male breast cancer (MBC) accounts for 1% of all breast cancer. Adult obesity and tallness are risk factors for MBC, but the role of adolescent fatness is largely unknown. We aimed to assess the association between body mass index (BMI) in adolescence and the incidence of MBC in a large cohort of 16-19 year-old Israeli males.

1,382,093 Jewish Israeli males aged 16-19 who underwent anthropometric measurements, a General Intelligence Test (GIT) and other examinations during 1967-2011, were followed up to 31.12.2012 for MBC incidence. Cox proportional hazards models assessed the association between adolescent BMI (as WHO BMI categories and as age-specific CDC percentiles) and time to MBC diagnosis, adjusting for sociodemographic covariates.

Of 100 MBC cases diagnosed during 29,386,233 person-years of follow-up, 97 were included in multivariable analyses. Compared to 'healthy' BMI (18.5-24.9kg/m²) and adjusted for year of birth, country of origin and GIT score, higher adolescent BMI was associated with higher MBC risk: hazard ratio (HR)=2.01 (95% confidence interval [CI]1.14-3.55, p=0.015) in overweight (25.0≤BMI<30.0kg/m²) adolescents; and HR=4.97 (95%CI 2.14-11.53, p=0.0002) in obese (BMI≥30.0kg/m²) adolescents. When CDC age-specific BMI percentiles were assessed results were similar and statistically significant for obesity. Additionally, low (vs. high) GIT score (HR=4.76, 95%CI 1.96-12.50, p=0.001) and European (vs. west-Asian) origin (HR=1.99, 95%CI 1.19-3.34, p=0.009) were independent predictors of MBC.

Measured adolescent overweight and obesity are associated with increased risk of MBC, suggesting a modifiable risk factor potentially allowing for early intervention. The novel association with cognitive function should be further explored. This article is protected by copyright. All rights reserved.

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Comparative Efficacy and Tolerability of Antiemetic Prophylaxis for Adult Highly Emetogenic Chemotherapy: A Network Meta-analysis of 143 Randomized Controlled Trials

Abstract

Chemotherapy-induced nausea and vomiting (CINV) is one of the commonest side-effects among cancer patients. However, there is lacking of hierarchical evidences comparing different antiemetics against highly emetogenic chemotherapy. Therefore, we conducted a network meta-analysis to investigate their comparative efficacy and tolerability. Randomized controlled trials that compared different antiemetic categories for adult highly emetogenic chemotherapy were included after searching PubMed, Web of Science, Embase and Cochrane Central. Acute-phase no emesis and no nausea were identified as primary endpoints. We made pairwise and hierarchical calculations by random-effects model. Effect sizes were presented by odds ratio and 95% confidential interval. Subgroup analysis was additionally performed. 143 randomized trials were included into pooled analysis, containing 22776 patients and 18 antiemetic categories. 5-HT₃ RA plus corticosteroid plus NK-1 RA plus other (5CNO) displayed best protection against both acute emesis (SUCRA: 99.7%) and nausea (95.6%). 5CNO (99.7%) and 5-HT₃ RA plus corticosteroid plus other (5CO, 85.3%) topped subgroup hierarchies for no-naivety and anthracycline plus cyclophosphamide (AC)-based studies. On the other hand, 5-HT₃ RA plus dopamine RA plus other (5DO) may be best fit for delayed emesis (92.0%) and nausea (92.7%). Subgroups featuring no-naivety and AC-based trials preferred 5DO (91.9%) and 5CN (88.6%) respectively. In addition, dopamine RA plus other (DO) had the lowest incidence of TRAE in most circumstances, except for AC-based subgroup where corticosteroid plus dopamine RA plus other (CDO) preponderated (69.2%). 5CNO and 5DO should be considered as first-line regimens against highly emetogenic chemotherapy induced acute and delayed CINV respectively. This article is protected by copyright. All rights reserved.

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Malaria, Epstein-Barr virus, vitamin A, and Burkitt's lymphoma: Response to Joob and Wiwanitkit

http://ift.tt/2gyPHp8

Anti-glypican-1 antibody-drug conjugate exhibits potent preclinical antitumor activity against glypican-1 positive uterine cervical cancer

Abstract

Glypican-1 (GPC1) is highly expressed in solid tumors, especially squamous cell carcinomas (SCCs), and is thought to be associated with disease progression. We explored the use of a GPC1-targeted antibody-drug conjugate (ADC) as a novel treatment for uterine cervical cancer. On immunohistochemical staining, high expression levels of GPC1 were detected in about 50% of uterine cervical cancer tissues and also in a tumor that had relapsed after chemoradiotherapy. Novel anti-GPC1 monoclonal antibodies were developed, and clone 01a033 was selected as the best antibody for targeted delivery of the cytotoxic agent monomethyl auristatin F (MMAF) into GPC1-positive cells. The anti-GPC1 antibody was conjugated with MMAF. On flow cytometry, HeLa and ME180 cervical cancer cells highly expressed GPC1, however, RMG-I ovarian clear cell cancer cell line showed weak expression. The GPC1-ADC was rapidly internalized into GPC1-expressing cells in vitro and was potently cytotoxic to cancer cells highly expressing GPC1. There were no inhibitory effects on cancer cells with low expression of GPC1. In a murine xenograft model, GPC1-ADC also had significant and potent tumor growth inhibition. GPC1-ADC–mediated G2/M phase cell cycle arrest was detected, indicating that the dominant antitumor effect in vivo was MMAF-mediated. The toxicity of GPC-ADC was tolerable within the therapeutic dose range in mice. Our data showed that GPC1-ADC has potential as a promising therapy for uterine cervical cancer. This article is protected by copyright. All rights reserved.

http://ift.tt/2yyMOvu

Cancer incidence in adults living in the vicinity of nuclear power plants in France, based on data from the French Network of Cancer Registries

Abstract

Nuclear power plants (NPPs) release toxic emissions into the environment that may affect neighboring populations. This ecologic study was designed to investigate the possibility of an excess incidence of cancer in the vicinity of French NPPs by examining the incidence by municipality of 12 types of cancer in the population aged 15 years and older during the 1995-2011 period. Population exposure to pollution was estimated on the basis of distance from towns of residence to the NPP. Using regression models, we assessed the risk of cancer in a 20-kilometer zone around NPPs and observed an excess incidence of bladder cancer (Relative Risk (RR), 95% Credibility Interval (95% CI)) in men and women (RR_men = 1.08; 95% CI: 1.00, 1.17 and RR_women = 1.19; 95% CI: 1.02, 1.39). Women living within the 20-km proximity areas had a significantly reduced risk of thyroid cancer (RR_women = 0.86; 95% CI: 0.77, 0.96). No excess risk of hematologic malignancies in either sex was seen. The higher than expected incidence of bladder cancer may be due to an excess incidence localized around the Flamanville NPP and the nearby La Hague nuclear waste treatment center, which is a source of chemical contaminants, many (including arsenic) of them known risk factors for bladder cancer. Differences in medical practices could explain the reduced risk of thyroid cancer. In this first study of adults living near NPPs in France, cancer incidence is significantly higher than in the references populations for one of the cancer types studied: bladder cancer. This article is protected by copyright. All rights reserved.

http://ift.tt/2gxz7Wy

Malaria, Epstein-Barr virus, vitamin A and Burkitt's lymphoma

http://ift.tt/2yyMLji

Targeting Class I Histone Deacetylases by the Novel Small Molecule Inhibitor 4SC-202 Blocks Oncogenic Hedgehog-GLI Signaling and Overcomes Smoothened Inhibitor Resistance

Abstract

Aberrant activation of Hedgehog (HH)/GLI signaling is causally involved in numerous human malignancies, including basal cell carcinoma (BCC) and medulloblastoma. HH pathway antagonists targeting Smoothened (SMO), an essential effector of canonical HH/GLI signaling, show significant clinical success in BCC patients and have recently been approved for the treatment of advanced and metastatic BCC. However, rapid and frequent development of drug resistance to SMO inhibitors (SMOi) together with severe side effects caused by prolonged SMOi treatment call for alternative treatment strategies targeting HH/GLI signaling downstream of SMO. In the present study, we report that 4SC-202, a novel clinically validated inhibitor of class I histone deacetylases (HDACs), efficiently blocks HH/GLI signaling. Notably, 4SC-202 treatment abrogates GLI activation and HH target gene expression in both SMOi-sensitive and resistant cells. Mechanistically, we propose that the inhibition of HDACs 1/2/3 is crucial for targeting oncogenic HH/GLI signaling, and that class I HDAC inhibitors either in combination with SMOi or as second line therapy may improve the treatment options for HH-associated malignancies with SMOi resistance. This article is protected by copyright. All rights reserved.

http://ift.tt/2gyibzf

Lifetime alcohol intake and risk of non-Hodgkin lymphoma: Findings from the Melbourne Collaborative Cohort Study

Abstract

Cohort studies have reported inconsistent evidence regarding alcohol intake and risk of non-Hodgkin lymphoma (NHL), mostly based on alcohol intake assessed close to study enrolment. We examined this association using alcohol intake measured from age 20 onwards. We calculated usual alcohol intake for 10-year periods from age 20 using recalled frequency and quantity of beverage-specific consumption for 37,990 participants aged 40-69 years from the Melbourne Collaborative Cohort Study. Cox regression was performed to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between alcohol intake (g/day) and NHL risk. After a mean follow-up of 19.3 years, 538 NHL cases were diagnosed. Approximately 80% of participants were either lifetime abstainers or consumed below 20 g of ethanol/day. All categories of lifetime alcohol intake were associated with about 20% lower incidence of NHL compared with lifetime abstention, but there was no evidence of a trend by amount consumed (HR = 0.97 per 10 g/day increment in intake, 95% CI: 0.92-1.03; p value=0.3). HRs for beer, wine and spirits were 0.91 (95% CI: 0.83-1.00; p value=0.05), 1.03 (95% CI: 0.94-1.12; p value=0.6) and 1.06 (95% CI: 0.83-1.37; p value=0.6), respectively, per 10 g/day increment in lifetime intake. There were no significant differences in associations between NHL subtypes. In this low-drinking cohort, we did not detect a dose-dependent association between lifetime alcohol intake and NHL risk. This article is protected by copyright. All rights reserved.

http://ift.tt/2yyhHAg

The joint effects of major lifestyle factors on colorectal cancer risk among Chinese men: A prospective cohort study

Abstract

Previous studies have suggested individual healthy lifestyle factors are related to lower risk of colorectal cancer. Their joint effects, however, have rarely been investigated. We aimed to assess the combined lifestyle impact on colorectal cancer risk and to estimate the population attributable risks of these lifestyle factors. Using data from the Shanghai Men's Health Study (2002-2013), we constructed healthy lifestyle index composing the following lifestyle factors: smoking, alcohol consumption, diet, waist-hip ratio and exercise participation. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Over a median of 9.28 years' follow-up, 671 colorectal cancer cases occurred (400 colon cancer and 274 rectal cancer) among 59503 men. Each increment of healthy lifestyle index was associated with a 17% lower risk of colorectal cancer (HR=0.83, 95%CI: 0.78, 0.89), 10% of colon cancer (HR=0.90, 95%CI: 0.83, 0.99) and 27% of rectal cancer (HR=0.73, 95%CI: 0.66, 0.82). If all men in the cohort followed a lifestyle as defined by these five factors, 21% colorectal cancer cases would have been prevented (PAR=21%, 95%CI: 4%, 36%). In conclusion, combined lifestyle factors are significantly related to lower risk of colorectal cancer and the effects are more pronounced on rectal cancer than on colon cancer. This article is protected by copyright. All rights reserved.

http://ift.tt/2gyIANr

Impact of gender-neutral or girls-only vaccination against human papillomavirus – Results of a community-randomized clinical trial (I)

Abstract

Human papillomavirus (HPV) vaccine is efficacious but the real-life effectiveness of gender-neutral and girls-only vaccination strategies is unknown. We report a community-randomized trial on the protective effectiveness [(PE) = vaccine efficacy (VE) + herd effect (HE)] of the two strategies among females in virtually HPV vaccination naïve population. We randomized 33 Finnish communities into Arm A) gender-neutral vaccination with AS04-adjuvanted HPV16/18 vaccine (11 communities), Arm B) HPV vaccination of girls and hepatitis B-virus (HBV) vaccination of boys (11 communities) or Arm C) gender-neutral HBV vaccination (11 communities). All resident 39,420 females and 40,852 males born 1992-95 were invited in 2007-09. Virtually all (99%) 12- to 15-year-old participating males (11,662) and females (20,513) received three doses resulting in uniform 20-30% male and 50% female vaccination coverage by birth cohort. Four years later (2010-14) 11,396 cervicovaginal samples obtained from 18.5 year-old women were tested for HPV DNA, and prevalence of cervical HPV infections by trial arm and birth cohort was the main outcome measure. VEs against HPV16/18 varied between 89.2% and 95.2% across birth cohorts in arms A and B. The VEs against non-vaccine types consistent with cross-protection were highest in those born 1994-95 for HPV45 (VE_A 82.8%; VE_B 86.1%) and for HPV31 (VE_A 77.6%, VE_B 84.6%). The HEs in the non HPV-vaccinated were statistically significant in those born 1994-95 for HPV18 (HE_A 51.0%; 95%CI 8.3-73.8, HE_B 47.2%; 6.5-70.2) and for HPV31/33 in arm A (HE_A 53.7%; 22.1-72.5). For HPV16 and 45 no significant herd effects were detected. PE estimates against HPV16/18 were similar by both strategies (PE_A 58.1%; 45.1-69.4; PE_B 55.7%; 42.9-66.6). PE estimates against HPV31/33 were higher by the gender-neutral vaccination (PE_A 60.5%; 43.6-73.4; PE_B 44.5%; 24.9-60.6). In conclusion, while gender-neutral strategy enhanced the effectiveness of HPV vaccination for cross-protected HPV types with low to moderate coverage, high coverage in males appears to be key to providing a substantial public health benefit also to unvaccinated females. Trial registration http://ift.tt/2gyZfQI NCT000534638 This article is protected by copyright. All rights reserved.

http://ift.tt/2yx6rDZ

Species-specific role of gene-adjacent retroelements in human and mouse gastric carcinogenesis

Abstract

Helicobacter pylori (HP) infection promotes the recruitment of bone marrow stem cells into chronic gastritis lesions. Some of these marrow stem cells can differentiate into gastric epithelial cells and neoplastic cells. We propose that HP-associated methylation could stabilize trans-differentiation of marrow-derived stem cells and that an unstable methylation status is associated with a risk of gastric cancer. Pathobiologic behavior of experimental mouse gastric cancer is mild compared to invasive and metastatic human gastric cancer. Differences in epigenetic stabilization of adult cell phenotypes between humans and mice could provide a foundation to explore the development of invasive and metastatic gastric cancer. Retroelements are highly repetitive sequences that play an essential role in the generation of species diversity. In this review, we analyzed retroelements adjacent to human and mouse housekeeping genes and proposed a possible epigenetic mechanism for HP-associated carcinogenesis. This article is protected by copyright. All rights reserved.

http://ift.tt/2yxgs4h

The involvement of lncRNAs in the development and progression of pancreatic cancer.

The involvement of lncRNAs in the development and progression of pancreatic cancer.

Cancer Biol Ther. 2017 Oct 20;:0

Authors: Duguang L, Jin H, Xiaowei Q, Peng X, Xiaodong W, Zhennan L, Jianjun Q, Jie Y

Abstract
Pancreatic cancer is one of the most malignant tumors that are difficult to diagnose at its early stage and there is no effective therapy. Recent studies uncovered that many non-protein-coding RNAs including the class of long noncoding RNAs (lncRNAs) are differentially expressed in various types of tumors and they are potent regulators of tumor progression and metastasis. LncRNA can mediate tumor initiation, proliferation, migration and metastasis through modulating epigenetic modification, alternative splicing, transcription, and protein translation. In this review, we discuss the molecular mechanism of lncRNAs in the involvement of tumor growth, survival, epithelial-mesenchymal transition, tumor microenvironment, cancer stem cells and chemoresistance in pancreatic ductal adenocarcinoma (PDAC).

PMID: 29053398 [PubMed - as supplied by publisher]

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