Surveillance imaging with FDG-PET/CT in the post-operative follow-up of stage 3 melanoma

Abstract

Background

As early detection of recurrent melanoma maximizes treatment options, patients usually undergo post-operative imaging surveillance, increasingly with FDG-PET/CT (PET). To assess this, we evaluated stage 3 melanoma patients who underwent prospectively applied and sub-stage-specific schedules of PET surveillance.

Patients and Methods

From 2009, patients with stage 3 melanoma routinely underwent PET +/- MRI brain scans via defined schedules based on sub-stage-specific relapse probabilities. Data were collected regarding patient characteristics and outcomes. Contingency analyses were performed of imaging outcomes.

Results

170 patients (stage 3A: 34; 3B: 93; 3C: 43) underwent radiological surveillance. Relapses were identified in 65 (38%) patients, of which 45 (69%) were asymptomatic. False-positive imaging findings occurred in 7%, and 6% had treatable second (non-melanoma) malignancies. Positive predictive values (PPV) of individual scans were 56% - 83%. Negative scans had predictive values of 89% - 96% for true non-recurrence (negative predictive values (NPV)) until the next scan. A negative PET at 18 months had NPVs of 80% - 84% for true non-recurrence at any time in the 47-month (median) follow-up period. Sensitivity and specificity of the overall approach of sub-stage-specific PET surveillance were 70% and 87%, respectively. Of relapsed patients, 33 (52%) underwent potentially curative resection and 10 (16%) remained disease-free after 24 months (median).

Conclusions

Application of sub-stage-specific PET in stage 3 melanoma enables asymptomatic detection of most recurrences, has high NPVs that may provide patient reassurance, and is associated with a high rate of detection of resectable and potentially curable disease at relapse.

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Cytology cell blocks are suitable for immunohistochemical testing for PD-L1 in lung cancer

Abstract

Background

PD-L1 immunohistochemistry (IHC) testing is usually performed on tissue blocks from core needle biopsy or surgical resections. In this study, we assessed the feasibility of using cytology cell blocks for PD-L1 IHC assay.

Methods

A total of 1419 consecutive cases of non-small cell lung cancer (NSCLC), including 371 cytology cell blocks, 809 small biopsies, and 239 surgical specimens, were included in the study. The cytology cell blocks were prepared with formalin only, methanol/alcohol only or both. PD-L1 expression was examined by staining with Dako PD-L1 IHC 22C3 pharmDx kit. A Tumor Proportion Score (TPS) was categorized as < 1%, 1-49% and ≥ 50% tumor cells. A total of 100 viable tumor cells were required for adequacy.

Results

Of the cytology cell blocks, 92% of the specimens had an adequate number of tumor cells, not significantly different from small biopsies. The rate of TPS ≥ 50% differed between sample types and was observed in 42% of cytology cell blocks versus 36% of small biopsies (P=0.04), and 29% of surgical resections (P=0.001). The fixative methods did not affect the immunostaining, with overall PD-L1 high expression (TPS≥50%) rates of 42% in formalin-fixed specimens versus 40% in specimens with combined fixation by methanol/alcohol and formalin (NS). The PD-L1 high expression rate was not associated with EGFR, ALK or KRAS molecular alterations. Higher stage (IV) was associated with higher PD-L1 TPS (P= 0.001).

Conclusion

Our results show that when the TPS ≥50% is used as the endpoint, PD-L1 IHC performs well with cytology cell blocks. Cell blocks should be considered as a valuable resource for PD-L1 testing in advanced NSCLC. The clinical significance of higher PD-L1 IHC scores in cytology specimens needs to be evaluated prospectively.

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Surveillance imaging with FDG-PET/CT in the post-operative follow-up of stage 3 melanoma

Abstract

Background

As early detection of recurrent melanoma maximizes treatment options, patients usually undergo post-operative imaging surveillance, increasingly with FDG-PET/CT (PET). To assess this, we evaluated stage 3 melanoma patients who underwent prospectively applied and sub-stage-specific schedules of PET surveillance.

Patients and Methods

From 2009, patients with stage 3 melanoma routinely underwent PET +/- MRI brain scans via defined schedules based on sub-stage-specific relapse probabilities. Data were collected regarding patient characteristics and outcomes. Contingency analyses were performed of imaging outcomes.

Results

170 patients (stage 3A: 34; 3B: 93; 3C: 43) underwent radiological surveillance. Relapses were identified in 65 (38%) patients, of which 45 (69%) were asymptomatic. False-positive imaging findings occurred in 7%, and 6% had treatable second (non-melanoma) malignancies. Positive predictive values (PPV) of individual scans were 56% - 83%. Negative scans had predictive values of 89% - 96% for true non-recurrence (negative predictive values (NPV)) until the next scan. A negative PET at 18 months had NPVs of 80% - 84% for true non-recurrence at any time in the 47-month (median) follow-up period. Sensitivity and specificity of the overall approach of sub-stage-specific PET surveillance were 70% and 87%, respectively. Of relapsed patients, 33 (52%) underwent potentially curative resection and 10 (16%) remained disease-free after 24 months (median).

Conclusions

Application of sub-stage-specific PET in stage 3 melanoma enables asymptomatic detection of most recurrences, has high NPVs that may provide patient reassurance, and is associated with a high rate of detection of resectable and potentially curable disease at relapse.

https://ift.tt/2HjjPAg

Cytology cell blocks are suitable for immunohistochemical testing for PD-L1 in lung cancer

Abstract

Background

PD-L1 immunohistochemistry (IHC) testing is usually performed on tissue blocks from core needle biopsy or surgical resections. In this study, we assessed the feasibility of using cytology cell blocks for PD-L1 IHC assay.

Methods

A total of 1419 consecutive cases of non-small cell lung cancer (NSCLC), including 371 cytology cell blocks, 809 small biopsies, and 239 surgical specimens, were included in the study. The cytology cell blocks were prepared with formalin only, methanol/alcohol only or both. PD-L1 expression was examined by staining with Dako PD-L1 IHC 22C3 pharmDx kit. A Tumor Proportion Score (TPS) was categorized as < 1%, 1-49% and ≥ 50% tumor cells. A total of 100 viable tumor cells were required for adequacy.

Results

Of the cytology cell blocks, 92% of the specimens had an adequate number of tumor cells, not significantly different from small biopsies. The rate of TPS ≥ 50% differed between sample types and was observed in 42% of cytology cell blocks versus 36% of small biopsies (P=0.04), and 29% of surgical resections (P=0.001). The fixative methods did not affect the immunostaining, with overall PD-L1 high expression (TPS≥50%) rates of 42% in formalin-fixed specimens versus 40% in specimens with combined fixation by methanol/alcohol and formalin (NS). The PD-L1 high expression rate was not associated with EGFR, ALK or KRAS molecular alterations. Higher stage (IV) was associated with higher PD-L1 TPS (P= 0.001).

Conclusion

Our results show that when the TPS ≥50% is used as the endpoint, PD-L1 IHC performs well with cytology cell blocks. Cell blocks should be considered as a valuable resource for PD-L1 testing in advanced NSCLC. The clinical significance of higher PD-L1 IHC scores in cytology specimens needs to be evaluated prospectively.

https://ift.tt/2v7uf0D

An overview of mammographic density and its association with breast cancer

Abstract

In 2017, breast cancer became the most commonly diagnosed cancer among women in the US. After lung cancer, breast cancer is the leading cause of cancer-related mortality in women. The breast consists of several components, including milk storage glands, milk ducts made of epithelial cells, adipose tissue, and stromal tissue. Mammographic density (MD) is based on the proportion of stromal, epithelial, and adipose tissue. Women with high MD have more stromal and epithelial cells and less fatty adipose tissue, and are more likely to develop breast cancer in their lifetime compared to women with low MD. Because of this correlation, high MD is an independent risk factor for breast cancer. Further, mammographic screening is less effective in detecting suspicious lesions in dense breast tissue, which can lead to late-stage diagnosis. Molecular differences between dense and non-dense breast tissues explain the underlying biological reasons for why women with dense breasts are at a higher risk for developing breast cancer. The goal of this review is to highlight the current molecular understanding of MD, its association with breast cancer risk, the demographics pertaining to MD, and the environmental factors that modulate MD. Finally, we will review the current legislation regarding the disclosure of MD on a traditional screening mammogram and the supplemental screening options available to women with dense breast tissue.

https://ift.tt/2v7qU1B

Involvement of prokineticin 2-expressing neutrophil infiltration in 5-fluorouracil-induced aggravation of breast cancer metastasis to lung

Adjuvant chemotherapy is used for human breast cancer patients, even after curative surgery of primary tumor, in order to prevent tumor recurrence primarily as a form of metastasis. However, anti-cancer drugs can accelerate metastasis in several mouse metastasis models. Hence, we examined the effects of post-surgical administration with 5-fluorouracil (5-FU), doxorubicin, and cyclophosphamide, on lung metastasis process, which developed after the resection of the primary tumor arising from the orthotopic injection of a mouse triple-negative breast cancer cell line, 4T1. Only 5-FU markedly increased the numbers and sizes of lung metastasis foci, with enhanced tumor cell proliferation and angiogenesis as evidenced by increases in Ki67-positive cell numbers and CD31-positive areas, respectively. 5-FU-mediated augmented lung metastasis was associated with increases in intrapulmonary neutrophil numbers and expression of neutrophilic chemokines, Cxcl1 and Cxcl2 in tumor cells, with few effects on intrapulmonary T cell or macrophage numbers. 5-FU enhanced Cxcl1 and Cxcl2 expression in 4T1 cells in a NF-kappaB-dependent manner. Moreover, the administration of a neutrophil-depleting antibody or a Cxcr2 antagonist, SB225002, significantly attenuated 5-FU-mediated enhanced lung metastasis with depressed neutrophil infiltration. Furthermore, infiltrating neutrophils and 4T1 cells abundantly expressed prokineticin-2 (Prok2) and its receptor, Prokr1, respectively. Finally, the administration of 5-FU after the resection of the primary tumor, failed to augment lung metastasis in the mice receiving Prokr1-deleted 4T1 cells. Collectively, 5-FU can enhance lung metastasis by inducing tumor cells to produce Cxcl1 and Cxcl2, which induced the migration of neutrophils expressing Prok2 with a capacity to enhance 4T1 cell proliferation.

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Involvement of prokineticin 2-expressing neutrophil infiltration in 5-fluorouracil-induced aggravation of breast cancer metastasis to lung

Adjuvant chemotherapy is used for human breast cancer patients, even after curative surgery of primary tumor, in order to prevent tumor recurrence primarily as a form of metastasis. However, anti-cancer drugs can accelerate metastasis in several mouse metastasis models. Hence, we examined the effects of post-surgical administration with 5-fluorouracil (5-FU), doxorubicin, and cyclophosphamide, on lung metastasis process, which developed after the resection of the primary tumor arising from the orthotopic injection of a mouse triple-negative breast cancer cell line, 4T1. Only 5-FU markedly increased the numbers and sizes of lung metastasis foci, with enhanced tumor cell proliferation and angiogenesis as evidenced by increases in Ki67-positive cell numbers and CD31-positive areas, respectively. 5-FU-mediated augmented lung metastasis was associated with increases in intrapulmonary neutrophil numbers and expression of neutrophilic chemokines, Cxcl1 and Cxcl2 in tumor cells, with few effects on intrapulmonary T cell or macrophage numbers. 5-FU enhanced Cxcl1 and Cxcl2 expression in 4T1 cells in a NF-kappaB-dependent manner. Moreover, the administration of a neutrophil-depleting antibody or a Cxcr2 antagonist, SB225002, significantly attenuated 5-FU-mediated enhanced lung metastasis with depressed neutrophil infiltration. Furthermore, infiltrating neutrophils and 4T1 cells abundantly expressed prokineticin-2 (Prok2) and its receptor, Prokr1, respectively. Finally, the administration of 5-FU after the resection of the primary tumor, failed to augment lung metastasis in the mice receiving Prokr1-deleted 4T1 cells. Collectively, 5-FU can enhance lung metastasis by inducing tumor cells to produce Cxcl1 and Cxcl2, which induced the migration of neutrophils expressing Prok2 with a capacity to enhance 4T1 cell proliferation.

https://ift.tt/2HtLk7J

FDA Expands Indication for Nilotinib [News in Brief]

Tyrosine kinase inhibitor approved for children with chronic myeloid leukemia.

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A survey on data reproducibility and the effect of publication process on the ethical reporting of laboratory research

Purpose: The successful translation of laboratory research into effective therapies is dependent upon the validity of peer-reviewed publications. However, several publications in recent years suggested that published scientific findings could only be reproduced 11-45% of the time. Multiple surveys attempted to elucidate the fundamental causes of data irreproducibility and underscored potential solutions; more robust experimental designs, better statistics, and better mentorship. However, no prior survey has addressed the role of the review and publication process on honest reporting. Experimental Design: We developed an anonymous online survey intended for trainees involved in bench research. The survey included questions related to mentoring/career development, research practice, integrity and transparency, and how the pressure to publish, and the publication process itself influence their reporting practices. Results: Responses to questions related to mentoring and training practices were largely positive, although an average of ~25% didn't seem to receive optimal mentoring. 39.2% revealed having been pressured by a principle investigator or collaborator to produce "positive" data. 62.8% admitted that the pressure to publish influences the way they report data. The majority of respondents did not believe that extensive revisions significantly improved the manuscript while adding to the cost and time invested. Conclusions: This survey indicates that trainees believe that the pressure to publish impacts honest reporting, mostly emanating from our system of rewards and advancement. The publication process itself impacts faculty and trainees and appears to influence a shift in their ethics from honest reporting ("negative data") to selective reporting, data falsification, or even fabrication.

https://ift.tt/2INsCrf

Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma

Purpose: Prexasertib, a checkpoint kinase 1 inhibitor, demonstrated single-agent activity in patients with advanced squamous cell carcinoma (SCC) in the dose-escalation portion of a Phase I study (NCT01115790). Monotherapy prexasertib was further evaluated in patients with advanced SCC. Experimental Design: Patients were given prexasertib 105 mg/m2 as a 1-hour infusion on day 1 of a 14-day cycle. Expansion cohorts were defined by tumor and treatment line. Safety, tolerability, efficacy, and exploratory biomarkers were analyzed. Results: Prexasertib was given to 101 patients, including 26 with SCC of the anus, 57 with SCC of the head and neck (SCCHN), and 16 with squamous cell non-small cell lung cancer (sqNSCLC). Patients were heavily pretreated (49% ≥3 prior regimens). The most common treatment-related adverse event was grade 4 neutropenia (71%); 12% of patients had febrile neutropenia. Median progression-free survival was 2.8 months (90% CI 1.9, 4.2) for SCC of the anus, 1.6 months (1.4, 2.8) for SCCHN, and 3.0 months (1.4, 3.9) for sqNSCLC. The clinical benefit rate at 3 months (complete response+partial response+stable disease) across tumors was 29% (23% SCC of the anus, 28% SCCHN, 44% sqNSCLC). Four patients with SCC of the anus had partial or complete response (overall response rate [ORR]=15%), and three patients with SCCHN had partial response (ORR=5%). Biomarker analyses focused on genes that altered DNA damage response or increased replication stress. Conclusions: Prexasertib demonstrated an acceptable safety profile and single-agent activity in patients with advanced SCC. The prexasertib maximum-tolerated dose of 105 mg/m² was confirmed as the recommended Phase II dose.

https://ift.tt/2qomBKu

A survey on data reproducibility and the effect of publication process on the ethical reporting of laboratory research

Purpose: The successful translation of laboratory research into effective therapies is dependent upon the validity of peer-reviewed publications. However, several publications in recent years suggested that published scientific findings could only be reproduced 11-45% of the time. Multiple surveys attempted to elucidate the fundamental causes of data irreproducibility and underscored potential solutions; more robust experimental designs, better statistics, and better mentorship. However, no prior survey has addressed the role of the review and publication process on honest reporting. Experimental Design: We developed an anonymous online survey intended for trainees involved in bench research. The survey included questions related to mentoring/career development, research practice, integrity and transparency, and how the pressure to publish, and the publication process itself influence their reporting practices. Results: Responses to questions related to mentoring and training practices were largely positive, although an average of ~25% didn't seem to receive optimal mentoring. 39.2% revealed having been pressured by a principle investigator or collaborator to produce "positive" data. 62.8% admitted that the pressure to publish influences the way they report data. The majority of respondents did not believe that extensive revisions significantly improved the manuscript while adding to the cost and time invested. Conclusions: This survey indicates that trainees believe that the pressure to publish impacts honest reporting, mostly emanating from our system of rewards and advancement. The publication process itself impacts faculty and trainees and appears to influence a shift in their ethics from honest reporting ("negative data") to selective reporting, data falsification, or even fabrication.

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Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma

Purpose: Prexasertib, a checkpoint kinase 1 inhibitor, demonstrated single-agent activity in patients with advanced squamous cell carcinoma (SCC) in the dose-escalation portion of a Phase I study (NCT01115790). Monotherapy prexasertib was further evaluated in patients with advanced SCC. Experimental Design: Patients were given prexasertib 105 mg/m2 as a 1-hour infusion on day 1 of a 14-day cycle. Expansion cohorts were defined by tumor and treatment line. Safety, tolerability, efficacy, and exploratory biomarkers were analyzed. Results: Prexasertib was given to 101 patients, including 26 with SCC of the anus, 57 with SCC of the head and neck (SCCHN), and 16 with squamous cell non-small cell lung cancer (sqNSCLC). Patients were heavily pretreated (49% ≥3 prior regimens). The most common treatment-related adverse event was grade 4 neutropenia (71%); 12% of patients had febrile neutropenia. Median progression-free survival was 2.8 months (90% CI 1.9, 4.2) for SCC of the anus, 1.6 months (1.4, 2.8) for SCCHN, and 3.0 months (1.4, 3.9) for sqNSCLC. The clinical benefit rate at 3 months (complete response+partial response+stable disease) across tumors was 29% (23% SCC of the anus, 28% SCCHN, 44% sqNSCLC). Four patients with SCC of the anus had partial or complete response (overall response rate [ORR]=15%), and three patients with SCCHN had partial response (ORR=5%). Biomarker analyses focused on genes that altered DNA damage response or increased replication stress. Conclusions: Prexasertib demonstrated an acceptable safety profile and single-agent activity in patients with advanced SCC. The prexasertib maximum-tolerated dose of 105 mg/m² was confirmed as the recommended Phase II dose.

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American Journal of Cancer Research; +16 new citations

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

American Journal of Cancer Research

These pubmed results were generated on 2018/04/11

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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Splanchnic Vein Thrombosis in the Myeloproliferative Neoplasms

Abstract

Purpose of Review

To review the epidemiology, diagnostic challenges, pathogenesis, and treatment strategies for patients with myeloproliferative neoplasm-associated splanchnic vein thrombosis.

Recent Findings

The epidemiology of myeloproliferative neoplasm-associated splanchnic vein thrombosis (MPN-SVT) has been well characterized. While typical MPN-associated thrombosis affects older patients and involves the arterial circulation, MPN-SVT mostly impacts younger women. An association with JAK2 V617F is well-known; recent studies have demonstrated only a weak association with CALR mutations. JAK inhibition may represent a novel treatment strategy, complementing anticoagulation, and management of portal hypertension.

Summary

While the epidemiology has been well characterized, more work is needed to identify novel contributors to disease pathogenesis, beyond the JAK2 V617F mutation itself, and endothelial compromise. Testing for MPN mutations in the setting of non-cirrhotic SVT is commonplace; JAK2 V617F is the most likely to be identified. Testing for CALR or MPL mutations requires clinical judgement, though not unreasonable. The mainstay of therapy is indefinite anticoagulation; the role of direct oral anticoagulants is unclear. JAK inhibition may play a role in addressing associated splenomegaly and portal hypertension.

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Splanchnic Vein Thrombosis in the Myeloproliferative Neoplasms

Abstract

Purpose of Review

To review the epidemiology, diagnostic challenges, pathogenesis, and treatment strategies for patients with myeloproliferative neoplasm-associated splanchnic vein thrombosis.

Recent Findings

The epidemiology of myeloproliferative neoplasm-associated splanchnic vein thrombosis (MPN-SVT) has been well characterized. While typical MPN-associated thrombosis affects older patients and involves the arterial circulation, MPN-SVT mostly impacts younger women. An association with JAK2 V617F is well-known; recent studies have demonstrated only a weak association with CALR mutations. JAK inhibition may represent a novel treatment strategy, complementing anticoagulation, and management of portal hypertension.

Summary

While the epidemiology has been well characterized, more work is needed to identify novel contributors to disease pathogenesis, beyond the JAK2 V617F mutation itself, and endothelial compromise. Testing for MPN mutations in the setting of non-cirrhotic SVT is commonplace; JAK2 V617F is the most likely to be identified. Testing for CALR or MPL mutations requires clinical judgement, though not unreasonable. The mainstay of therapy is indefinite anticoagulation; the role of direct oral anticoagulants is unclear. JAK inhibition may play a role in addressing associated splenomegaly and portal hypertension.

https://ift.tt/2qqOQro

More Thoughts on Standards and Reproducibility

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 3, Page 85-86, April 2018.


https://ift.tt/2GSjbdx

Effects of Repeated Aurora-A siRNA Transfection on Cilia Generation and Proliferation of SK-MES-1 or A549 Cells

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 3, Page 110-117, April 2018.


https://ift.tt/2qqRHRb

CLR 125 Auger Electrons for the Targeted Radiotherapy of Triple-Negative Breast Cancer

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 3, Page 87-95, April 2018.


https://ift.tt/2GRXlH4

MiR-17 Regulates Prostate Cancer Cell Proliferation and Apoptosis Through Inhibiting JAK-STAT3 Signaling Pathway

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 3, Page 103-109, April 2018.


https://ift.tt/2qpFLz1

Constructing a Novel Hypoxia-Inducible Bidirectional shRNA Expression Vector for Simultaneous Gene Silencing in Colorectal Cancer Gene Therapy

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 3, Page 118-123, April 2018.


https://ift.tt/2GRX86K

Odynophagia and neck pain after exercise

Description

A previously healthy, non-asthmatic, non-smoker, 16-year-old male came for medical attention because of odynophagia and pain located at anterior cervical area and upper retrosternal area, increasing with swallowing and deep breathing, that begun after physical exercise at gymnastic class. The adolescent also mentioned a felling of air bubbles running up and down that area. There was no history of local trauma. He referred stuffed nose and mild cough but no other respiratory complaints or fever. Physical examination was unremarkable, with normal auscultation and no alterations on cervical and thoracic examination. Lateral soft tissue neck X-ray revealed free air in retropharyngeal space (figure 1, arrows). Chest X-ray showed a small amount of air in the upper mediastinum. Blood count was normal, and C reactive protein was negative. Mycoplasma pneumoniae IgM was negative. The patient was treated with high concentration oxygen and oral analgesia. The next day, he...

https://ift.tt/2JCb0j9

Food-dependent exercise-induced anaphylaxis

Food-dependent exercise-induced anaphylaxis (FDEIAn), first reported in 1979, is a condition defined by the consumption of a trigger food with temporally related exercise that results in an immediate hypersensitivity (type 1) reaction in the setting of the trigger food being tolerated independent of exercise and exercise being tolerated in the absence of trigger food consumption. The most common trigger food in the west is wheat and shellfish in Asia. The exact mechanism of FDEIAn is unknown, though several hypotheses exist. Cofactors such as non-steroidal anti-inflammatory drug use, alcohol consumption and others have been associated with reported cases.

https://ift.tt/2GSFvQ1

Inadvertent inflation of Foley catheter balloon with contrast: an error that caused unnecessary apprehensions

Description 

A 30-year-old male patient underwent percutaneous nephrolithotomy (PCNL) for a 3.5 cm right renal calculus. As per our institutional protocol he underwent a check X-ray the next day. The relatives of the patient immediately came to us asking whether some residual fragments of the calculus were there in the urinary bladder. When we reviewed the X-ray film, there was a radio-opaque shadow with a smooth contour in the region of urinary bladder. On careful examination this shadow was continuous with a radio-opaque line along the Foley catheter (figure 1). We immediately removed the Foley catheter and did another check X-ray. The shadow had disappeared. We then realised that the catheter's balloon was inflated with contrast solution prepared for fluoroscopy-guided puncture during PCNL. We acknowledged this error to the patient and his relatives and explained them how sorry we were for their anxiety, following which they were...

https://ift.tt/2JCaXDZ

Arthroscopic reduction and fixation of a lateral inverted osteochondral fracture of the talus ('LIFT)

Some ankle sprains hide important lesions beyond the classic lateral ligament complex injuries. The lateral inverted osteochondral fracture of the talus (LIFT) represents a rare osteochondral lesion, whose diagnosis relies on a high clinical suspicion followed by correct image study interpretation. We present a successful arthroscopic fixation of a LIFT lesion in a 45-year-old active man. At 8 months follow-up, the patient was pain free and able to return to his daily activities without limitation. The imagiological study showed osteochondral fragment consolidation with no signs of hardware failure. This midterm results reassemble the need for early diagnosis and correct treatment to achieve a good outcome in these complex and rare osteochondral lesions.

https://ift.tt/2GUqDRr

Rare and unexpected complication after a malpositioned nasogastric tube in a neonate

Description

A full-term newborn boy was admitted to the high dependency unit at the age of 4 hours with signs of respiratory distress, tachypnoea and recession with low oxygen saturation. There was no perinatal history of concerns; delivery was normal and uneventful, but the mother was colonised with Group B streptococcus.

A plan was made on admission for a chest X-ray, a nasogastric tube (NGT) insertion and antibiotics. NGT was placed by a senior neonatal nurse without incident, followed by chest X-ray primarily looking for respiratory causes of the respiratory distress. This however revealed that the NGT was malposed into the right main bronchus (figure 1). There were no signs of choking or cough at the time of insertion. NGT was then pulled out and a new one reinserted in a satisfactory position and confirmed on a repeat chest X-ray (figure 2). A right-sided small and...

https://ift.tt/2Jysmxr

Orbital metastasis from an occult breast carcinoma (T0, N1, M1)

The authors report a case of an orbital metastasis from an occult breast carcinoma. A 66-year-old woman presented with a growing left orbital tumour. Orbital CT scan was consistent with lymphoma. However, ocular pathology revealed small neoplastic cells showing an 'indian file pattern' suggestive of metastatic carcinoma and immunohistochemistry was positive for CK7, CK CAM5.2 and oestrogen receptor. A systemic evaluation was then performed with mammogram, breast ultrasound and MRI considered normal. An exhaustive systemic evaluation revealed multiple bone lesions, a right axillary lymph node lesion, which presented the same pattern on pathology and immunohistochemistry, with no evidence of a primary tumour. A diagnosis of a metastatic lobular carcinoma of the breast (T0, N1, M1) was made and the patient was started on chemotherapy and adjuvant hormonal therapy.

https://ift.tt/2GPNEVr

Treatment-refractory ALK-positive inflammatory myofibroblastic tumour of the oral cavity

We present a challenging case of a previously healthy 23-year-old man who developed an inflammatory myofibroblastic tumour of the hard palate, harbouring a rearrangement of the anaplastic lymphoma kinase (ALK) locus. Despite surgical intervention, radiotherapy and ALK-inhibition therapy, the tumour recurred locally and metastasised to regional lymph nodes, and the patient passed away roughly 9 months after diagnosis from local progression. The rapid progression of this patient's disease and its resistance to treatment demonstrate the potentially aggressive clinical course of inflammatory myofibroblastic tumours. ALK-inhibition therapy was unsuccessful in this ALK-positive tumour, highlighting the need for further investigation of markers predictive of disease progression and treatment response.

https://ift.tt/2JCaO3p

Sphingomonas paucimobilis empyema caused by remote foreign body aspiration

Empyema secondary to foreign body aspiration is rare in adults. We present a case of empyema in a 77-year-old male patient related to a remote aspiration event during a dental procedure. A CT of the chest and bronchoscopy confirmed that a metallic foreign body was located within the right lower lobe bronchus. His pleural fluid culture revealed Sphingomonas paucimobilis which is a low-virulent opportunistic gram-negative bacilli and rarely causes infection. The patient received meropenem followed by levofloxacin and recovered uneventfully. The attempt of foreign body removal was failed due to chronic inflammation, and the patient refused further surgical management.

https://ift.tt/2EEzXGZ

Peripherally inserted central catheter (PICC) placement: beware of the bends

Description 

The peripherally inserted central catheter (PICC) is used as a long-term vascular access to deliver medications and venous nutrition. The PICC tip terminates close to the heart or in one of the great vessels—the superior vena cava or the inferior vena cava. Catheter tip confirmation is usually achieved by plain radiography. We describe a case of a 9-month-old boy with complex congenital heart disease (heterotaxy syndrome, polysplenia type) who underwent pulmonary artery banding to reduce pulmonary blood flow to control heart failure symptoms. PICC was placed in the left femoral vein during the postoperative period. PICC tip confirmation was obtained by anteroposterior plain abdominal radiograph (figure 1), which demonstrated catheter tip bending at T12. The lateral radiograph of the abdomen showed that the PICC courses posteriorly into the lumbar venous plexus (figure 2). The ascending lumbar veins arises at L5–S1 from the common iliac vein and drains into...

https://ift.tt/2JBkM50

Improvement of thoracic myelopathy following bariatric surgery in an obese patient

Revision spine surgery is extremely challenging in super-super obese patients (body mass index (BMI) ≥60 kg/m²). This is the first report describing how bariatric surgery was useful for a super-super obese patient with progressing myelopathy. A 44-year-old man with a BMI of 62.9 kg/m² presented with an ambulatory disorder caused by thoracic ossification of the posterior longitudinal ligament (T7–8). Before this paraparesis, he had undergone four spinal operations, and was not considered a good candidate for a fifth spine surgery. At the time of the fourth operation, he had reached a maximum weight of 205 kg (BMI 69.3 kg/m²). Instead, he underwent a laparoscopic sleeve gastrectomy. Sixteen months later, his body weight had decreased to BMI 35.2 kg/m², and he could walk without a walker. In addition to reducing our patient's load, a 'non-operative' form of dekyphosis due to altered thoracic spinal alignment secondary to weight loss may explain the improvement in his myelopathy.

https://ift.tt/2EEzVyR

Spontaneous rectus sheath haematoma due to cough on apixaban

Description 

A 69-year-old woman on apixaban for 4 years due to her atrial fibrillation presented with severe left lower abdominal pain. She was discharged from the hospital 4 days prior after treatment for influenza and had finished a course of oseltamivir. She did not receive any heparin products and was continued on apixaban during that admission. A few hours before presentation, she reported coughing severely with sudden onset of excruciating abdominal pain. She denied trauma or injury to the abdomen. On exam, she was alert, normotensive and tachycardic, with significant left lower quadrant tenderness in the abdomen. Laboratory results were significant for decreased haemoglobin from 15.2 to 12.9 g/dL. CT of the abdomen showed acute left inferior rectus abdominis muscle haematoma (7.5 cm), along with stable and unchanged left adnexal cystic lesion (figure 1). Apixaban was discontinued, and the patient was closely monitored in the hospital with supportive care....

https://ift.tt/2JBkL0W

Pseudoaneurysm of the gastroduodenal artery: an unusual cause for hyperamylasaemia

A 79-year-old man was admitted electively for investigation of weight loss. While he was an inpatient, he developed severe epigastric pain and an initial blood test revealed an acutely raised amylase (>2000) and deranged liver function tests. A contrast CT angiography showed a large haematoma adjacent to the duodenum, spreading in the retroperitoneal space, arising from a 2 cm bleeding pseudoaneurysm in the region of the gastroduodenal artery. Due to his underlying comorbidities, he was deemed unfit for surgical repair and he had coil embolisation with successful haemostasis. The gastroduodenal artery aneurysms are rare and constitute 1.5% of all visceral artery aneurysms. They can be an incidental finding or they can present with haemorrhagic shock, abdominal pain and rarely with obstructive jaundice or hyperamylasaemia. The diagnosis is usually made with an angiography. Variable treatment options are available depending on the patient's fitness and haemodynamic stability.

https://ift.tt/2EDTvLA

Single coronary artery with bicuspid aortic valve

Description

A 45-year-old man with known history of coronary artery disease and bicuspid aortic valve (BAV) (figure 1) was admitted for worsening symptoms of angina. Coronary angiogram showed single coronary artery arising from the left cusp, trifurcating into right coronary artery, left anterior descending (LAD) and left circumflex artery (LCx) (figure 2). No course of the left main coronary artery between the aortic root and the pulmonary artery was noted. There was obstructive disease in proximal LAD (70%), first diagonal artery (80%) and proximal LCx (70%). Peak gradient of 51 mm Hg across the BAV was registered. He underwent bypass graft surgery along with an aortic valve replacement successfully.

Figure 1

Transoesophageal echocardiogram. Parasternal short axis view revealing bicuspid aortic valve (BAV). Red arrows pointing at aortic valve cusps.

Figure 2

(A) Left anterior oblique (LAO) caudal view....

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Evaluation of prognostic models developed using standardised image features from different PET automated segmentation methods

Abstract

Background

Prognosis in oesophageal cancer (OC) is poor. The 5-year overall survival (OS) rate is approximately 15%. Personalised medicine is hoped to increase the 5- and 10-year OS rates. Quantitative analysis of PET is gaining substantial interest in prognostic research but requires the accurate definition of the metabolic tumour volume. This study compares prognostic models developed in the same patient cohort using individual PET segmentation algorithms and assesses the impact on patient risk stratification.

Consecutive patients (n = 427) with biopsy-proven OC were included in final analysis. All patients were staged with PET/CT between September 2010 and July 2016. Nine automatic PET segmentation methods were studied. All tumour contours were subjectively analysed for accuracy, and segmentation methods with < 90% accuracy were excluded. Standardised image features were calculated, and a series of prognostic models were developed using identical clinical data. The proportion of patients changing risk classification group were calculated.

Results

Out of nine PET segmentation methods studied, clustering means (KM2), general clustering means (GCM3), adaptive thresholding (AT) and watershed thresholding (WT) methods were included for analysis. Known clinical prognostic factors (age, treatment and staging) were significant in all of the developed prognostic models. AT and KM2 segmentation methods developed identical prognostic models. Patient risk stratification was dependent on the segmentation method used to develop the prognostic model with up to 73 patients (17.1%) changing risk stratification group.

Conclusion

Prognostic models incorporating quantitative image features are dependent on the method used to delineate the primary tumour. This has a subsequent effect on risk stratification, with patients changing groups depending on the image segmentation method used.

https://ift.tt/2GPEts1

Evaluation of prognostic models developed using standardised image features from different PET automated segmentation methods

Abstract

Background

Prognosis in oesophageal cancer (OC) is poor. The 5-year overall survival (OS) rate is approximately 15%. Personalised medicine is hoped to increase the 5- and 10-year OS rates. Quantitative analysis of PET is gaining substantial interest in prognostic research but requires the accurate definition of the metabolic tumour volume. This study compares prognostic models developed in the same patient cohort using individual PET segmentation algorithms and assesses the impact on patient risk stratification.

Consecutive patients (n = 427) with biopsy-proven OC were included in final analysis. All patients were staged with PET/CT between September 2010 and July 2016. Nine automatic PET segmentation methods were studied. All tumour contours were subjectively analysed for accuracy, and segmentation methods with < 90% accuracy were excluded. Standardised image features were calculated, and a series of prognostic models were developed using identical clinical data. The proportion of patients changing risk classification group were calculated.

Results

Out of nine PET segmentation methods studied, clustering means (KM2), general clustering means (GCM3), adaptive thresholding (AT) and watershed thresholding (WT) methods were included for analysis. Known clinical prognostic factors (age, treatment and staging) were significant in all of the developed prognostic models. AT and KM2 segmentation methods developed identical prognostic models. Patient risk stratification was dependent on the segmentation method used to develop the prognostic model with up to 73 patients (17.1%) changing risk stratification group.

Conclusion

Prognostic models incorporating quantitative image features are dependent on the method used to delineate the primary tumour. This has a subsequent effect on risk stratification, with patients changing groups depending on the image segmentation method used.

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Intracranial control and survival outcome of tyrosine kinase inhibitor (TKI) alone versus TKI plus radiotherapy for brain metastasis of epidermal growth factor receptor-mutant non-small cell lung cancer

Abstract

Introduction

The efficacy of tyrosine kinase inhibitors (TKIs) with and without radiotherapy (RT) has not been determined in patients with brain metastases from epidermal growth factor receptor-mutant TKI naïve non-small cell lung cancer (NSCLC).

Methods

Between 2008 and 2016, 586 patients were diagnosed with NSCLC and treated with TKIs at a hospital in Seoul, South Korea; 81 of these patients met the eligibility criteria for our study. Outcomes analyzed included intracranial progression (ICP), neurological death, and overall survival (OS).

Results

The 2-year cumulative incidence of ICP was 36.5% in the TKI plus RT group and 62.2% in the TKI alone group (P = 0.006). The chronological pattern analysis indicated that 64.3% of ICP developed within 12 months of the start of TKI treatment in the TKI alone group. The multivariate analysis revealed that treatment group (P = 0.003) and duration of TKI treatment ≤ 12 months (P < 0.001) were significantly associated with ICP. However, no significant differences were observed in the 2-year OS rate (P = 0.267) or the 2-year cumulative incidence of neurological death (P = 0.740).

Conclusions

Cumulative incidence of ICP was significantly lower with TKI plus RT than with TKI alone; however, there was no significant difference in OS or neurological death. Deferring brain RT may not compromise neurologic and survival outcome in selected patients, but close magnetic resonance imaging follow-up is recommended for patients who defer brain RT.

https://ift.tt/2IIlGM0

Acceptance and compliance of TTFields treatment among high grade glioma patients

Abstract

Background

Tumor treating fields (TTFields) significantly prolong both progression-free and overall survival in patients with newly diagnosed glioblastoma (GBM). TTFields are delivered to the brain tumor via skin transducer arrays and should be applied for a minimum of 18 h per day (≥ 75% compliance). This may cause limited acceptance by patients because of obstacles in daily routine. So far, there are limited data on factors influencing therapy acceptance and compliance.

Methods

In this retrospective study, fourty-one patients with primary GBM or recurrent high grade glioma (rHGG) have been treated with TTFields in our department. Compliance reports were generated at the monthly routine check of the device. We investigated demographic data, stage of disease and therapy duration in regard to treatment compliance.

Results

Thirty percent of patients with primary diagnosis of GBM were informed about TTFields. Acceptance rate among these patients was 36%. In this study, TTFields were prescribed in newly diagnosed GBM patients (57%) and in rHGG. Mean treatment compliance was 87% in the total population independent of age, sex and stage of disease. Compliance was not negatively correlated with time on treatment.

Conclusion

TTFields are effective in newly diagnosed GBM, therefore acceptance and compliance is important for GBM treatment. We experienced moderate acceptance rate for TTFields, which is influenced by factors such as social support, comorbidities and independence in daily life. Overall therapy compliance lies above 75% and is not influenced by age, sex, stage of disease or duration of therapy. Improved patient consultation strategies will increase acceptance and compliance for better outcome.

https://ift.tt/2HhP2DC

Severe postoperative complications decrease overall and disease free survival in pancreatic ductal adenocarcinoma after pancreaticoduodenectomy

Publication date: Available online 10 April 2018
Source:European Journal of Surgical Oncology
Author(s): Jean Lubrano, Philippe Bachelier, François Paye, Yves Patrice Le Treut, Laurence Chiche, Antonio Sa-Cunha, Olivier Turrini, Benjamin Menahem, Guy Launoy, Jean-Robert Delpero
BackgroundPostoperative complications influence overall and disease free survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma is still a matter of debate and controversy.MethodsThe outcome of 942 consecutive patients, from the multicentric study of the French Association of Surgery, between January 2004 and December 2009 was analyzed. Perioperative data, including severe complications (grade III and above), were used in univariate and multivariate analysis to assess their influence on overall and disease free survival. Recurrence and its location were investigated as well.ResultsMedian overall and disease free survival were 24 and 19 months respectively. Postoperative complications occurred in 444 patients (47%) with 18.3% of severe complications. On multivariate analysis, severe complications, positive lymph node status and R1-R2 resection were independent prognostic factors for both overall and disease free survival. The median overall survival decreased from 25 to 22 months (p=0.005) and disease free survival from 21 to 16 months (p=0.02) if severe complications occurred. Severe complications were independent prognostic factor of recurrence (p<0.001).ConclusionsSevere complications significantly alter both overall and disease free survival and are an independent factor of recurrence.



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Preoperative nutritional status assessment predicts postoperative outcomes in patients with surgically resected non-small cell lung cancer

Publication date: Available online 11 April 2018
Source:European Journal of Surgical Oncology
Author(s): Ricard Ramos, Ernest Nadal, Inma Peiró, Cristina Masuet-Aumatell, Ivan Macia, Francisco Rivas, Gabriela Rosado, Pau Rodriguez, Anna Ureña, Susana Padrones, Samantha Aso, Carlos Deniz, Arturo Navarro, Ignacio Escobar
BackgroundAs nutritional status plays an important role in outcomes after surgery, this study evaluated the association between preoperative nutritional status (NS) and postoperative outcomes after major resection for lung cancer.MethodsWe identified 219 patients with a diagnosis of cancer who underwent pulmonary resection from 2010 to 2012. Preoperative NS was assessed by anthropometric and biological parameters, body mass index (BMI), and the Nutritional Risk Index (NRI). We stratified this population into 4 BMI groups: underweight, normal weight, overweight and obese and 4 NRI groups: well-nourished; mildly malnourished; moderately malnourished and severely malnourished. The outcomes measured were postoperative complications; 30-day postoperative mortality; hospital length of stay (LOS), overall survival (OS) and disease-free survival (DFS). We performed both unadjusted analysis and adjusted multivariable analysis, controlling for statistically significant variables.ResultsMean BMI and NRI were, respectively, 26.5±4.3 and 112.4±3.3. There were no significant differences between BMI categories and resection type, pathological stage, or overall postoperative complications. By contrast, significant differences (p <0.05) in postoperative complications were observed among the NRI groups. LOS was longer in underweight and/or malnourished patients. In terms of OS, we found no significant differences according to NRI and BMI; however, patients with underweight had significantly shorter DFS compared with patients with overweight and obesity (log-rank p-value =0.001).ConclusionNS as measured by the NRI is an independent predictor of the risk of postsurgical complications, regardless of clinicopathologic characteristics. NRI might therefore be an useful tool for identifying early-stage lung cancer patients at risk for postoperative complications.



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Intracranial control and survival outcome of tyrosine kinase inhibitor (TKI) alone versus TKI plus radiotherapy for brain metastasis of epidermal growth factor receptor-mutant non-small cell lung cancer

Abstract

Introduction

The efficacy of tyrosine kinase inhibitors (TKIs) with and without radiotherapy (RT) has not been determined in patients with brain metastases from epidermal growth factor receptor-mutant TKI naïve non-small cell lung cancer (NSCLC).

Methods

Between 2008 and 2016, 586 patients were diagnosed with NSCLC and treated with TKIs at a hospital in Seoul, South Korea; 81 of these patients met the eligibility criteria for our study. Outcomes analyzed included intracranial progression (ICP), neurological death, and overall survival (OS).

Results

The 2-year cumulative incidence of ICP was 36.5% in the TKI plus RT group and 62.2% in the TKI alone group (P = 0.006). The chronological pattern analysis indicated that 64.3% of ICP developed within 12 months of the start of TKI treatment in the TKI alone group. The multivariate analysis revealed that treatment group (P = 0.003) and duration of TKI treatment ≤ 12 months (P < 0.001) were significantly associated with ICP. However, no significant differences were observed in the 2-year OS rate (P = 0.267) or the 2-year cumulative incidence of neurological death (P = 0.740).

Conclusions

Cumulative incidence of ICP was significantly lower with TKI plus RT than with TKI alone; however, there was no significant difference in OS or neurological death. Deferring brain RT may not compromise neurologic and survival outcome in selected patients, but close magnetic resonance imaging follow-up is recommended for patients who defer brain RT.

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Acceptance and compliance of TTFields treatment among high grade glioma patients

Abstract

Background

Tumor treating fields (TTFields) significantly prolong both progression-free and overall survival in patients with newly diagnosed glioblastoma (GBM). TTFields are delivered to the brain tumor via skin transducer arrays and should be applied for a minimum of 18 h per day (≥ 75% compliance). This may cause limited acceptance by patients because of obstacles in daily routine. So far, there are limited data on factors influencing therapy acceptance and compliance.

Methods

In this retrospective study, fourty-one patients with primary GBM or recurrent high grade glioma (rHGG) have been treated with TTFields in our department. Compliance reports were generated at the monthly routine check of the device. We investigated demographic data, stage of disease and therapy duration in regard to treatment compliance.

Results

Thirty percent of patients with primary diagnosis of GBM were informed about TTFields. Acceptance rate among these patients was 36%. In this study, TTFields were prescribed in newly diagnosed GBM patients (57%) and in rHGG. Mean treatment compliance was 87% in the total population independent of age, sex and stage of disease. Compliance was not negatively correlated with time on treatment.

Conclusion

TTFields are effective in newly diagnosed GBM, therefore acceptance and compliance is important for GBM treatment. We experienced moderate acceptance rate for TTFields, which is influenced by factors such as social support, comorbidities and independence in daily life. Overall therapy compliance lies above 75% and is not influenced by age, sex, stage of disease or duration of therapy. Improved patient consultation strategies will increase acceptance and compliance for better outcome.

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Impact of smoking history on the outcomes of women with early-stage breast cancer: a secondary analysis of a randomized study

Abstract

To assess the impact of smoking history on the outcomes of early-stage breast cancer patients treated with sequential anthracyclines–taxanes in a randomized study. This is a secondary analysis of patient-level data of 1242 breast cancer patients referred for adjuvant chemotherapy in the BCIRG005 clinical trial. Overall survival was assessed according to smoking history through Kaplan–Meier analysis. Univariate and multivariate Cox regression analyses of factors affecting overall and relapse-free survival were subsequently conducted. Factors that were evaluated included: age, performance status, number of chemotherapy cycles, T stage, lymph node ratio, estrogen receptor status, adjuvant radiotherapy and smoking history. Kaplan–Meier analysis of overall survival according to smoking status (ever smoker vs. never smoker) was conducted. There was a trend toward a better overall survival among never smokers compared to ever smokers; however, it was not statistically significant (P = 0.098). The following factors were associated with better overall survival in multivariate analysis: older age (P = 0.011), complete chemotherapy course (P = 0.002), lower T stage (P < 0.0001), lower lymph node ratio (P < 0.0001) and positive estrogen receptor status (P = 0.006). Otherwise, the following factors were associated with better relapse-free survival in multivariate analysis: older age (P = 0.001), never smoking status (P = 0.021), lower T stage (P = 0.028), lower lymph node ratio (P < 0.0001) and positive estrogen receptor status (P < 0.0001). Early-stage breast cancer patients with a positive smoking history experienced worse relapse-free survival compared to never smokers. Physicians managing breast cancer patients should prioritize discussion about the benefits of smoking cessation when counseling their patients.

https://ift.tt/2HiWkHz

Histone deacetylase SIRT6 inhibits glioma cell growth through down-regulating NOTCH3 expression

Abstract

Gliomas are the most common brain tumors of the central nervous system. In this study, we investigated the molecular mechanisms and biological function of SIRT6 in human gliomas. The expression levels of SIRT6 in glioma tissues and cells were analyzed by qRT-PCR and western blot analysis. CCK8 and clonogenicity assays were performed to detect the cell proliferation. Furthermore, the migration and invasion of glioma cells were examined by transwell assays. It was found that the expression of SIRT6 was significantly lower in human glioma tissues or cell lines compared with the normal brain tissue or NHA. Up-regulated SIRT6 significantly decreased cell proliferation, migration and invasion of U87 and U251 cells. By contrast, knockdown of SIRT6 dramatically increased cell proliferation, migration and invasion of U87 and U251 cells. Moreover, over expression of NOTCH3 significantly increased the cell proliferation, migration, and invasion of U87 and U251 cells. However, these effects were abolished after overexpression of SIRT6. These results suggest that SIRT6 may suppress cell proliferation, migration, and invasion via inhibition of the NOTCH3 signaling pathway in glioma.

https://ift.tt/2GU7nTQ

MiR-31 regulates the function of diabetic endothelial progenitor cells by targeting Satb2

Abstract

Endothelial malfunctions in patients with diabetes are known to result in vascular diseases, and endothelial progenitor cells (EPCs) are indispensable for the functional preservation of the vascular endothelium. MicroRNA-31 (miR-31) has been found to be able to modulate the differentiation of stem cells. However, it is still unclear how miR-31 functions in diabetic EPCs. The aim of this study was to investigate how miR-31 regulates diabetic EPC function. In the current study, miR-31 expression was compared between normal and diabetic EPCs. Satb2 was recognized as a functionally related target of miR-31 in EPCs according to computational prediction. We also explored the role of miR-31 in terms of its anti-apoptotic effects. A remarkable elevation in miR-31 expression was found in diabetic EPCs, and this elevated expression resulted in suppressed cell proliferation under high glucose. It was also found that miR-31 targets Satb2, leading to the anti-apoptotic effect and maintenance of the functions of EPCs. Furthermore, knockdown of Satb2 exhibited an inhibitory effect on proliferation and migration of EPCs in both healthy and diabetic subjects, which showed the same trend as miR-31 overexpression. Conversely, overexpression of Satb2 showed the opposite effect. Moreover, overexpression of Satb2 attenuated the miR-31-induced migration and colony-forming ability reduction and apoptosis induction of EPCs in both healthy and diabetic subjects. In diabetic EPCs, elevated glucose level was found to up-regulate miR-31 expression, which in turn enhanced the malfunction and death of EPCs. In conclusion, our results indicate that up-regulation of miR-31 may underlie endothelial dysfunction in diabetes by targeting Satb2.

https://ift.tt/2Hs6KCd

An EGF receptor-targeting amphinase recombinant protein mediates anti-tumor activity in vitro and in vivo

Abstract

Utilizing cytotoxic proteins linked to tumor targeting molecules as anti-tumor drugs is a promising approach. However, most cytotoxins derived from bacteria or plants have inherent problems such as large molecular weights and they trigger a strong immune system reaction, which leads to drug failure and serious side effects. Amphinase (Amph) is a ribonuclease with a low molecular weight that is found in northern leopard frog oocytes. It has strong cytotoxicity against tumor cell lines in vitro and weak immunogenicity in vivo, and is a promising candidate in the development of targeted drugs. Transforming growth factor-α (TGF-α) that binds to the epidermal growth factor receptor (EGFR) is being used as a targeting molecule for the treatment of EGFR high-expressing tumors. In this study, we expressed and purified a recombinant amphinase and its TGF-α fusion protein (AGT) separately from Escherichia coli. AGT exhibited more significant cytotoxicity in vitro on EGFR high-expressing tumor cell lines, and stronger anti-tumor effects in vivo. This fusion protein also exhibited unusual thermostability, low in vivo immunogenicity, and side effects. Our results provide a new entry point for the development of novel, highly efficient anti-tumor targeting biological agents with low immunogenicity.

https://ift.tt/2INbpOt

An ultrasensitive biological probe enhanced RT-IPCR assay for detecting benzo[a]pyrene in environmental samples based on the specific polyclonal antibody

Abstract

Benzo[a]pyrene (BaP), a type of polycyclic aromatic hydrocarbon, is widely distributed in the environment. In this study, BaP immunogen and coating antigen were respectively prepared by different methods, and the specific antibody targeting the BaP analyte was obtained. Moreover, gold nanoparticles modified with the specific polyclonal antibody and thiol-capped DNA were prepared as biological probes. Based on the work above, an ultrasensitive biological probe enhanced real-time immuno-polymerase chain reaction (BP-rt-iPCR) assay was developed to detect BaP in several environmental samples. Under optimal conditions, the proposed method was used to detect BaP with a linearity ranging from 5 pg/l to 50 ng/l. The limit of detection was 1.63 pg/l. The recovery rates of the spiked samples ranged from 92.12% to 109.76% and the coefficients of variation were 7.53%–11.06%. This immunoassay was successfully used to detect BaP in environmental samples, and the BaP detection results were consistent with those obtained using high performance liquid chromatography, indicating that the BP-rt-iPCR method is accurate and reliable, and has great potential to detect trace amounts of BaP.

https://ift.tt/2HuVyVa

Impact of smoking history on the outcomes of women with early-stage breast cancer: a secondary analysis of a randomized study

Abstract

To assess the impact of smoking history on the outcomes of early-stage breast cancer patients treated with sequential anthracyclines–taxanes in a randomized study. This is a secondary analysis of patient-level data of 1242 breast cancer patients referred for adjuvant chemotherapy in the BCIRG005 clinical trial. Overall survival was assessed according to smoking history through Kaplan–Meier analysis. Univariate and multivariate Cox regression analyses of factors affecting overall and relapse-free survival were subsequently conducted. Factors that were evaluated included: age, performance status, number of chemotherapy cycles, T stage, lymph node ratio, estrogen receptor status, adjuvant radiotherapy and smoking history. Kaplan–Meier analysis of overall survival according to smoking status (ever smoker vs. never smoker) was conducted. There was a trend toward a better overall survival among never smokers compared to ever smokers; however, it was not statistically significant (P = 0.098). The following factors were associated with better overall survival in multivariate analysis: older age (P = 0.011), complete chemotherapy course (P = 0.002), lower T stage (P < 0.0001), lower lymph node ratio (P < 0.0001) and positive estrogen receptor status (P = 0.006). Otherwise, the following factors were associated with better relapse-free survival in multivariate analysis: older age (P = 0.001), never smoking status (P = 0.021), lower T stage (P = 0.028), lower lymph node ratio (P < 0.0001) and positive estrogen receptor status (P < 0.0001). Early-stage breast cancer patients with a positive smoking history experienced worse relapse-free survival compared to never smokers. Physicians managing breast cancer patients should prioritize discussion about the benefits of smoking cessation when counseling their patients.

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A Skeptical Approach to the Management of Persistent Oral Ulceration in a Child

The diagnosis of oral lesions is sometimes difficult due to both the clinician's limited experience with the conditions that may cause the lesions and their similar appearances, especially in children. Correctly establishing a definitive diagnosis is of major importance to clinicians who manage patients with oral mucosal diseases. In patients with Fanconi anaemia (FA), oral ulcers occur frequently, which are quite variable, and may lead to a misdiagnosis or failure to diagnose. Here, we report the case of a 15-year-old boy who was examined for squamous cell cancer of the tongue and diagnosed as having FA without any haematological manifestations. While surgery could not be done, both radiotherapy and chemotherapy had to be decreased. He died of progressive disease 6 months after the diagnosis. Unexplained ulcers in a child with a duration longer than 2 weeks should be further evaluated, especially for FA, even without the presence of anaemia.

https://ift.tt/2HitxCZ

MODUL—a multicenter randomized clinical trial of biomarker-driven maintenance therapy following first-line standard induction treatment of metastatic colorectal cancer: an adaptable signal-seeking approach

Abstract

Purpose

The old approach of one therapeutic for all patients with mCRC is evolving with a need to target specific molecular aberrations or cell-signalling pathways. Molecular screening approaches and new biomarkers are required to fully characterize tumours, identify patients most likely to benefit, and predict treatment response.

Methods

MODUL is a signal-seeking trial with a design that is highly adaptable, permitting modification of different treatment cohorts and inclusion of further additional cohorts based on novel evidence on new compounds/combinations that emerge during the study.

Results

MODUL is ongoing and its adaptable nature permits timely and efficient recruitment of patients into the most appropriate cohort. Recruitment will take place over approximately 5 years in Europe, Asia, Africa, and South America. The design of MODUL with ongoing parallel/sequential treatment cohorts means that the overall size and duration of the trial can be modified/prolonged based on accumulation of new data.

Conclusions

The early success of the current trial suggests that the design may provide definitive leads in a patient-friendly and relatively economical trial structure. Along with other biomarker-driven trials that are currently underway, it is hoped that MODUL will contribute to the continuing evolution of clinical trial design and permit a more 'tailored' approach to the treatment of patients with mCRC.

https://ift.tt/2HdSq2t

MODUL—a multicenter randomized clinical trial of biomarker-driven maintenance therapy following first-line standard induction treatment of metastatic colorectal cancer: an adaptable signal-seeking approach

Abstract

Purpose

The old approach of one therapeutic for all patients with mCRC is evolving with a need to target specific molecular aberrations or cell-signalling pathways. Molecular screening approaches and new biomarkers are required to fully characterize tumours, identify patients most likely to benefit, and predict treatment response.

Methods

MODUL is a signal-seeking trial with a design that is highly adaptable, permitting modification of different treatment cohorts and inclusion of further additional cohorts based on novel evidence on new compounds/combinations that emerge during the study.

Results

MODUL is ongoing and its adaptable nature permits timely and efficient recruitment of patients into the most appropriate cohort. Recruitment will take place over approximately 5 years in Europe, Asia, Africa, and South America. The design of MODUL with ongoing parallel/sequential treatment cohorts means that the overall size and duration of the trial can be modified/prolonged based on accumulation of new data.

Conclusions

The early success of the current trial suggests that the design may provide definitive leads in a patient-friendly and relatively economical trial structure. Along with other biomarker-driven trials that are currently underway, it is hoped that MODUL will contribute to the continuing evolution of clinical trial design and permit a more 'tailored' approach to the treatment of patients with mCRC.

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GDF15 promotes the proliferation of cervical cancer cells by phosphorylating AKT1 and Erk1/2 through the receptor ErbB2

Growth differentiation factor 15 (GDF15) is a member of the TGF-β superfamily, and evidence suggests that a substantial amount of GDF15 is secreted in various human cancers, such as ovarian cancer, prostate ca...

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Iron-dependent cell death as executioner of cancer stem cells

This commentary highlights the findings by Mai, et al. that ironomycin, derivatives of salinomycin, exhibited more potent and selective therapeutic activity against breast cancer stem cells by accumulating and...

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Successful Clarithromycin Monotherapy in a Patient with Primary Follicular Lymphoma of the Duodenum

Primary follicular lymphoma of the duodenum (FL-D) constitutes a rare subtype of extranodal follicular lymphoma with a usually indolent course. To date, no distinct treatment recommendations have been defined for those patients. We report the case of a 58-year-old male patient presenting with endoscopically assessed, symptomatic FL-D who was treated with clarithromycin monotherapy in analogy to recent data for mucosa-associated lymphoid tissue lymphoma. Each treatment cycle consisted of clarithromycin 500 mg twice daily for 3 weeks followed by a 2-week break. After four cycles of treatment, the patient showed a very good response with normal macroscopic findings confirmed by endosonographic examination and only focal minimal residual disease of lymphoma persisting in the histological assessment. The patient is currently asymptomatic and without treatment for 24+ months. As clarithromycin combines antimicrobial and direct antiproliferative effects mediated through a variety of pleiotropic mechanisms, this appears to be an interesting treatment approach for indolent lymphoma, particularly in those where a chronic infectious background cannot be completely ruled out, i.e., gastrointestinal manifestations. We suggest further investigation of this treatment approach.
Case Rep Oncol 2018;11:239–245

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Acute epithelial toxicity is prognostic for improved prostate cancer response to radiotherapy: a retrospective multi-centre cohort study

Publication date: Available online 11 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Thomas Eade, Ananya Choudhury, Alan Pollack, Matthew Abramowitz, Felix M. Chinea, Linxin Guo, Jason Kennedy, Sandra Louw, George Hruby, Andrew Kneebone, Catharine West
IntroductionPatients with germline mutations in their DNA repair pathway are at risk of increased toxicity from radiotherapy. These patients could also have radiosensitive cancer cells. We hypothesised that increased acute toxicity, measured using subdomains reflective of epithelial cell damage, will be associated with reduced late biochemical failure, as a surrogate for tumor radiosensitivity.Methods and MaterialsThe study design was retrospective with discovery and validation cohorts involving routinely collected data. Eligible patients had prostate cancer, underwent radiotherapy with curative intent and had acute toxicity assessed prospectively. The discovery cohort was from a single institution. Genitourinary and gastrointestinal acute toxicity related to epithelial cell damage (hematuria, dysuria, proctitis or mucus) were related to freedom from late biochemical failure (FFBF; nadir+2). The validation cohort were from two separate institutions.Results503 patients were included in the discovery cohort and 658 patients in the validation cohort. In the validation cohort, patients with acute radiation toxicity reflecting epithelial damage, had a longer FFBF on both univariate (HR 0.37; p=0.004) and multivariate (HR 0.45; p=0.035) analysis. The impact of acute toxicity on late FFBF appeared to be greater in patients treated with androgen deprivation (HR 0.19) than those without (HR 0.48).ConclusionPatients reporting acute radiation toxicity reflective of epithelial cell damage during definitive radiotherapy for prostate cancer have significantly longer FFBF, consistent with an underlying genetic link between normal tissue and tumor radiosensitivity.

Teaser

We hypothesised that increased early radiation toxicity, measured using specific subdomains, is associated with improved local control following prostate radiotherapy. We used a discovery cohort to select the specific subdomains of acute GU and GI toxicity most likely to represent epithelial damage, and subsequently confirmed in patients from 2 other institutions that acute toxicity significantly reduces late biochemical failure. This confirms there is a potential genetic link between acute radiation toxicity and cancer outcomes.


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Acute epithelial toxicity is prognostic for improved prostate cancer response to radiotherapy: a retrospective multi-centre cohort study

Publication date: Available online 11 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Thomas Eade, Ananya Choudhury, Alan Pollack, Matthew Abramowitz, Felix M. Chinea, Linxin Guo, Jason Kennedy, Sandra Louw, George Hruby, Andrew Kneebone, Catharine West
IntroductionPatients with germline mutations in their DNA repair pathway are at risk of increased toxicity from radiotherapy. These patients could also have radiosensitive cancer cells. We hypothesised that increased acute toxicity, measured using subdomains reflective of epithelial cell damage, will be associated with reduced late biochemical failure, as a surrogate for tumor radiosensitivity.Methods and MaterialsThe study design was retrospective with discovery and validation cohorts involving routinely collected data. Eligible patients had prostate cancer, underwent radiotherapy with curative intent and had acute toxicity assessed prospectively. The discovery cohort was from a single institution. Genitourinary and gastrointestinal acute toxicity related to epithelial cell damage (hematuria, dysuria, proctitis or mucus) were related to freedom from late biochemical failure (FFBF; nadir+2). The validation cohort were from two separate institutions.Results503 patients were included in the discovery cohort and 658 patients in the validation cohort. In the validation cohort, patients with acute radiation toxicity reflecting epithelial damage, had a longer FFBF on both univariate (HR 0.37; p=0.004) and multivariate (HR 0.45; p=0.035) analysis. The impact of acute toxicity on late FFBF appeared to be greater in patients treated with androgen deprivation (HR 0.19) than those without (HR 0.48).ConclusionPatients reporting acute radiation toxicity reflective of epithelial cell damage during definitive radiotherapy for prostate cancer have significantly longer FFBF, consistent with an underlying genetic link between normal tissue and tumor radiosensitivity.

Teaser

We hypothesised that increased early radiation toxicity, measured using specific subdomains, is associated with improved local control following prostate radiotherapy. We used a discovery cohort to select the specific subdomains of acute GU and GI toxicity most likely to represent epithelial damage, and subsequently confirmed in patients from 2 other institutions that acute toxicity significantly reduces late biochemical failure. This confirms there is a potential genetic link between acute radiation toxicity and cancer outcomes.


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Bioinformatic analysis reveals the key pathways and genes in early-onset breast cancer

Abstract

Early-onset breast cancer is the most prevalent cancer in the female. To identify the differentially expressed genes and the key signaling pathways in early-onset breast cancer, we have carried out the bioinformatic analysis of an RNA array dataset in the GEO database, GSE109169, which was acquired from early-onset breast cancer patient. A total of 118 differentially expressed genes in early-onset breast cancer were significantly changed compared with that in adjacent normal tissues. Most of these genes are classified into three categories: signaling molecule, enzyme modulator, and hydrolase. Gene ontology terms reveal that most of these genes are involved in cellular and metabolic processes, biological regulation, binding and catalytic activities, and receptor regulation. Protein–protein interaction network was constructed and has two highly enriched modules: one with up-regulated genes and the other with down-regulated genes. The singling pathways are mainly enriched in the cellular immune system, lipid metabolism and other types of metabolic pathways. Finally, we have plotted the Kaplan–Meier curves of two up-regulated and two down-regulated genes for the overall survival prediction in breast cancer. These results greatly expand the current view of early-onset breast cancer and shed light on the discovery of drug candidates and the improvement for the prognosis.

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Bioinformatic analysis reveals the key pathways and genes in early-onset breast cancer

Abstract

Early-onset breast cancer is the most prevalent cancer in the female. To identify the differentially expressed genes and the key signaling pathways in early-onset breast cancer, we have carried out the bioinformatic analysis of an RNA array dataset in the GEO database, GSE109169, which was acquired from early-onset breast cancer patient. A total of 118 differentially expressed genes in early-onset breast cancer were significantly changed compared with that in adjacent normal tissues. Most of these genes are classified into three categories: signaling molecule, enzyme modulator, and hydrolase. Gene ontology terms reveal that most of these genes are involved in cellular and metabolic processes, biological regulation, binding and catalytic activities, and receptor regulation. Protein–protein interaction network was constructed and has two highly enriched modules: one with up-regulated genes and the other with down-regulated genes. The singling pathways are mainly enriched in the cellular immune system, lipid metabolism and other types of metabolic pathways. Finally, we have plotted the Kaplan–Meier curves of two up-regulated and two down-regulated genes for the overall survival prediction in breast cancer. These results greatly expand the current view of early-onset breast cancer and shed light on the discovery of drug candidates and the improvement for the prognosis.

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Bexarotene-Induced Hypertriglyceridemia: A Case Report

We present a case of a patient with cutaneous T-cell lymphoma started on bexarotene 300 mg/m² due to progressing disease. The patient experienced good clinical response, but unfortunately, she developed rapid and profound hypertriglyceridemia. Although hypertriglyceridemia occurs in high incidence with bexarotene therapy, management recommendations are scarce. Due to the rise in triglycerides, atorvastatin 10 mg daily was initiated in combination with fenofibrate 120 mg daily. Triglycerides continued to increase, so the patient was instructed to take atorvastatin 40 mg, fenofibrate 120 mg, and to hold bexarotene for 2 weeks. After the 2-week break, bexarotene was restarted at 150 mg/m².
Case Rep Oncol 2018;11:234–238

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Hermes

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Radiologists in Iraq and Afghanistan: a meager, but heartfelt thank-you

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Pediatric Radiology Continuing Medical Education Activity

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Hermes

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Radiologists in Iraq and Afghanistan: a meager, but heartfelt thank-you

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Pediatric Radiology Continuing Medical Education Activity

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Personalized cancer vaccines: adjuvants are important, too

Abstract

Therapeutic cancer vaccines have shown limited clinical efficacy so far. Nevertheless, in the meantime, our understanding of immune cell function and the interactions of immune cells with growing tumors has advanced considerably. We are now in a position to invest this knowledge into the design of more powerful vaccines and therapy combinations aimed at increasing immunogenicity and decreasing tumor-induced immunosuppression. This review focuses essentially on peptide-based human vaccines. We will discuss two aspects that are critical for increasing their intrinsic immunogenicity: the selection of the antigen(s) to be targeted, and the as yet unmet need for strong adjuvants.

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The Impact of Dose and Simultaneous Use of Acid-Reducing Agents on the Effectiveness of Vemurafenib in Metastatic BRAF V600 Mutated Melanoma: a Retrospective Cohort Study

Abstract

Background

The impact of dose and simultaneous use of acid-reducing agents (ARAs) on the effectiveness of vemurafenib is unknown.

Objectives

To determine the association between progression of metastatic BRAF V600 mutated melanoma and (1) dose reductions of vemurafenib and (2) simultaneous use of vemurafenib and ARAs.

Patient and Methods

A retrospective cohort study of 112 first-line vemurafenib users for melanoma was conducted (March 2012–March 2016), using electronic patient records and pharmacy dispensing records of a Dutch academic hospital. Cox regression analysis was used to estimate the risk of progression with full-dose (n = 64) versus reduced-dose vemurafenib (n = 48) and with simultaneous use of vemurafenib and ARAs (n = 35) versus vemurafenib alone (n = 77). Analyses were adjusted for age and sex.

Results

In total, disease progression occurred in 55% of treated patients on vemurafenib, with a median progression-free survival of 6.0 (95% confidence interval [CI] 5.0–6.9) months. Compared to patients on vemurafenib alone, there was no increased risk of progression among patients requiring vemurafenib at a reduced dose or among patients receiving simultaneous therapy with vemurafenib and ARAs. In addition, there was no increased risk of progression among patients who used reduced-dose vemurafenib and ARAs versus those receiving full-dose vemurafenib as sole therapy. However, a tendency for progression was observed among patients who used full-dose vemurafenib and ARAs versus full-dose vemurafenib alone (adjusted hazard ratio [HRa] 2.37; 95% CI 0.97–5.76), which became statistically significant in a sensitivity analysis (HRa 4.56; 95% CI 1.51–13.75).

Conclusions

There was no association between the use of vemurafenib in a reduced dose or the simultaneous use of vemurafenib and ARAs and the risk of progression. In addition, there was no association between the simultaneous use of vemurafenib in a reduced dose and ARAs and the risk of progression. However, patients tolerating  full-dose vemurafenib simultaneously with ARAs might have an increased risk of progression. This finding requires prospective validation.

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Personalized cancer vaccines: adjuvants are important, too

Abstract

Therapeutic cancer vaccines have shown limited clinical efficacy so far. Nevertheless, in the meantime, our understanding of immune cell function and the interactions of immune cells with growing tumors has advanced considerably. We are now in a position to invest this knowledge into the design of more powerful vaccines and therapy combinations aimed at increasing immunogenicity and decreasing tumor-induced immunosuppression. This review focuses essentially on peptide-based human vaccines. We will discuss two aspects that are critical for increasing their intrinsic immunogenicity: the selection of the antigen(s) to be targeted, and the as yet unmet need for strong adjuvants.

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Theory and methodology: essential tools that can become dangerous belief systems

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Personalized cancer vaccines: adjuvants are important, too

Abstract

Therapeutic cancer vaccines have shown limited clinical efficacy so far. Nevertheless, in the meantime, our understanding of immune cell function and the interactions of immune cells with growing tumors has advanced considerably. We are now in a position to invest this knowledge into the design of more powerful vaccines and therapy combinations aimed at increasing immunogenicity and decreasing tumor-induced immunosuppression. This review focuses essentially on peptide-based human vaccines. We will discuss two aspects that are critical for increasing their intrinsic immunogenicity: the selection of the antigen(s) to be targeted, and the as yet unmet need for strong adjuvants.

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Update on PARP Inhibitors in Breast Cancer

Opinion statement

The single agent activity of PARP inhibitors (PARPi) in germline BRCA mutated (gBRCAm) breast and ovarian cancer suggests untapped potential for this new class of drug in breast cancer. The US Food and Drug Administration has approved three PARPi (olaparib, rucaparib, and niraparib) so far to treat certain ovarian cancers, including those with gBRCAm and olaparib for treatment of gBRCAm breast cancers. Several PARPi are now under clinical development for breast cancer in the various treatment settings. Recently, two phase III trials of olaparib (OlympiaD) and talazoparib (EMBRACA) demonstrated 3-month progression-free survival improvement with PARPi compared to physician's choice single agent chemotherapy in metastatic gBRCAm breast cancer. To date, PARPi seems less efficacious in metastatic breast cancer patients than those with BRCA mutated platinum-sensitive recurrent ovarian cancer, perhaps reflecting the biologic heterogeneity and low somatic BRCA mutation rate in breast cancer. The use of PARPi is gradually evolving, including combination strategies with chemotherapy, targeted agents, radiotherapy, or immunotherapy in women with and without gBRCAm. The role of predictive biomarkers, including molecular signatures and homologous recombination repair deficiency scores based on loss of heterozygosity and other structural genomic aberrations, will be crucial to identify a subgroup of patients who may have benefit from PARPi. An improved understanding of the mechanisms underlying PARPi clinical resistance will also be important to enable the development of new approaches to increase efficacy. This is a field rich in opportunity, and the coming years should see a better understanding of which breast cancer patients we should treat with PARPi and where these agents should come in over the course of treatment.

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Update on PARP Inhibitors in Breast Cancer

Opinion statement

The single agent activity of PARP inhibitors (PARPi) in germline BRCA mutated (gBRCAm) breast and ovarian cancer suggests untapped potential for this new class of drug in breast cancer. The US Food and Drug Administration has approved three PARPi (olaparib, rucaparib, and niraparib) so far to treat certain ovarian cancers, including those with gBRCAm and olaparib for treatment of gBRCAm breast cancers. Several PARPi are now under clinical development for breast cancer in the various treatment settings. Recently, two phase III trials of olaparib (OlympiaD) and talazoparib (EMBRACA) demonstrated 3-month progression-free survival improvement with PARPi compared to physician's choice single agent chemotherapy in metastatic gBRCAm breast cancer. To date, PARPi seems less efficacious in metastatic breast cancer patients than those with BRCA mutated platinum-sensitive recurrent ovarian cancer, perhaps reflecting the biologic heterogeneity and low somatic BRCA mutation rate in breast cancer. The use of PARPi is gradually evolving, including combination strategies with chemotherapy, targeted agents, radiotherapy, or immunotherapy in women with and without gBRCAm. The role of predictive biomarkers, including molecular signatures and homologous recombination repair deficiency scores based on loss of heterozygosity and other structural genomic aberrations, will be crucial to identify a subgroup of patients who may have benefit from PARPi. An improved understanding of the mechanisms underlying PARPi clinical resistance will also be important to enable the development of new approaches to increase efficacy. This is a field rich in opportunity, and the coming years should see a better understanding of which breast cancer patients we should treat with PARPi and where these agents should come in over the course of treatment.

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β-Catenin-driven adrenocortical carcinoma is characterized with immune exclusion

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Crocin induces autophagic apoptosis in hepatocellular carcinoma by inhibiting Akt/mTOR activity

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