AHNAK suppresses tumour proliferation and invasion by targeting multiple pathways in triple-negative breast cancer

Abstract

Background

AHNAK, also known as desmoyokin, is a giant protein with the molecular size of approximately 700 kDa and exerts diverse functions in different types of cancer.

Results

In the present study, we demonstrated that AHNAK mRNA levels were down-regulated in 7 out of 8 human breast cancer cell lines, especially in triple - negative breast cancer (TNBC) cell lines. Moreover, in patients with TNBC, the expression of AHNAK gene was inversely correlated with the tumor status (P = 0.015), lymph node status (P < 0.001), lymph node (LN) infiltration (P < 0.001) and TNM stage (P < 0.001). Moreover, down-regulated AHNAK expression was considered an independent prognostic factor associated with the poor survival of patients with TNBC. Overexpression of AHNAK in two TNBC cell lines, MDA-MB-231 and BT549, suppressed the in vitro TNBC cell proliferation and colony formation, and inhibited the in vivo TNBC xenograft growth and lung metastasis. The tumor suppressing effect of AHNAK in TNBC was associated with the AKT/MAPK signaling pathway and Wnt/β-catenin pathway. Consistent results were observed when AHNAK was knockdown in BT20 and MDA-MB-435 cells.

Conclusions

Taken together, our results suggest that AHNAK acts as a tumor suppressor that negatively regulates TNBC cell proliferation, TNBC xenograft growth and metastasis via different signaling pathways.

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Lysophosphatidylcholine acyltransferase 1 upregulation and concomitant phospholipid alterations in clear cell renal cell carcinoma

Abstract

Background

The involvement of lipid metabolism in tumourigenesis and the progression of clear cell renal cell carcinoma (ccRCC) have been reported. However, the role of phospholipid profile alterations in ccRCC has not yet been systematically explored. In the present study, we compared the phospholipid compositions between ccRCC and paired normal renal tissues.

Methods

The phospholipid compositions of paired ccRCC and normal renal tissues were evaluated using liquid chromatography tandem mass spectrometry (LC/MS/MS). To evaluate the mRNA and protein levels of lysophosphatidylcholine acyltransferase (LPCAT), which converts lysophosphatidylcholine (LPC) to phosphatidylcholine (PC), qRT-PCR, western blotting and immunohistochemistry were performed. The correlations of LPCAT1 expression with clinicopathological features and prognosis were assessed. In addition, siRNAs were used to knockdown LPCAT1 expression in ccRCC cell lines, and its effect on cell proliferation, cell cycle, migration and invasion were investigated.

Results

The phospholipid compositions of ccRCC and normal renal tissues were significantly different. Multiple LPC species were decreased and corresponding PC species were increased in cancer tissues. The mRNA and protein levels of LPCAT1 were up-regulated in ccRCC tissues compared with normal renal tissues, and LPCAT1 expression was significantly correlated with unfavourable pathological features (higher tumour grade, higher TNM stage and larger tumour size) and overall survival. In cell line experiments, LPCAT1 knockdown depleted PCs, inhibited cell proliferation, migration and invasion and induced cell cycle arrest at the G0/G1 phase.

Conclusion

Selective changes in PC and LPC composition were observed in ccRCC tissues. The overexpression of LPCAT1 promotes the development and progression of ccRCC, likely through the conversion of LPC to PC.

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AHNAK suppresses tumour proliferation and invasion by targeting multiple pathways in triple-negative breast cancer

Abstract

Background

AHNAK, also known as desmoyokin, is a giant protein with the molecular size of approximately 700 kDa and exerts diverse functions in different types of cancer.

Results

In the present study, we demonstrated that AHNAK mRNA levels were down-regulated in 7 out of 8 human breast cancer cell lines, especially in triple - negative breast cancer (TNBC) cell lines. Moreover, in patients with TNBC, the expression of AHNAK gene was inversely correlated with the tumor status (P = 0.015), lymph node status (P < 0.001), lymph node (LN) infiltration (P < 0.001) and TNM stage (P < 0.001). Moreover, down-regulated AHNAK expression was considered an independent prognostic factor associated with the poor survival of patients with TNBC. Overexpression of AHNAK in two TNBC cell lines, MDA-MB-231 and BT549, suppressed the in vitro TNBC cell proliferation and colony formation, and inhibited the in vivo TNBC xenograft growth and lung metastasis. The tumor suppressing effect of AHNAK in TNBC was associated with the AKT/MAPK signaling pathway and Wnt/β-catenin pathway. Consistent results were observed when AHNAK was knockdown in BT20 and MDA-MB-435 cells.

Conclusions

Taken together, our results suggest that AHNAK acts as a tumor suppressor that negatively regulates TNBC cell proliferation, TNBC xenograft growth and metastasis via different signaling pathways.

http://ift.tt/2q82a5z

Lysophosphatidylcholine acyltransferase 1 upregulation and concomitant phospholipid alterations in clear cell renal cell carcinoma

Abstract

Background

The involvement of lipid metabolism in tumourigenesis and the progression of clear cell renal cell carcinoma (ccRCC) have been reported. However, the role of phospholipid profile alterations in ccRCC has not yet been systematically explored. In the present study, we compared the phospholipid compositions between ccRCC and paired normal renal tissues.

Methods

The phospholipid compositions of paired ccRCC and normal renal tissues were evaluated using liquid chromatography tandem mass spectrometry (LC/MS/MS). To evaluate the mRNA and protein levels of lysophosphatidylcholine acyltransferase (LPCAT), which converts lysophosphatidylcholine (LPC) to phosphatidylcholine (PC), qRT-PCR, western blotting and immunohistochemistry were performed. The correlations of LPCAT1 expression with clinicopathological features and prognosis were assessed. In addition, siRNAs were used to knockdown LPCAT1 expression in ccRCC cell lines, and its effect on cell proliferation, cell cycle, migration and invasion were investigated.

Results

The phospholipid compositions of ccRCC and normal renal tissues were significantly different. Multiple LPC species were decreased and corresponding PC species were increased in cancer tissues. The mRNA and protein levels of LPCAT1 were up-regulated in ccRCC tissues compared with normal renal tissues, and LPCAT1 expression was significantly correlated with unfavourable pathological features (higher tumour grade, higher TNM stage and larger tumour size) and overall survival. In cell line experiments, LPCAT1 knockdown depleted PCs, inhibited cell proliferation, migration and invasion and induced cell cycle arrest at the G0/G1 phase.

Conclusion

Selective changes in PC and LPC composition were observed in ccRCC tissues. The overexpression of LPCAT1 promotes the development and progression of ccRCC, likely through the conversion of LPC to PC.

http://ift.tt/2r6KFzz

Current FDA-approved injection pattern versus targeted peripheral nerve–directed injection pattern. The current FDA-approved injection pattern includes chemodenervation of 7 head and neck muscle groups (A–C). The total units of BOTOX injected for each site bilaterally include: corrugators 10U, procerus 5U, frontalis 20U (A), temporalis 40U (B), occipitalis 30U, cervical paraspinal 20U, and trapezius 30U (C). By comparison, peripheral nerve–directed BOTOX injection targets fewer sites with a smaller total quantity of BOTOX (D–F). The total units of BOTOX injected for each site bilaterally include: supraorbital nerve/supratrochlear nerve 25U (D), zygomaticotemporal nerve 37.5U (E), and greater occipital nerve 50U (F). Source Targeted Peripheral Nerve-directed Onabotulinumtoxin A Injection for Effective Long-term Therapy for Migraine Headache

http://otorhinolaryngology-crete.blogspot.com/2017/05/current-fda-approved-injection-pattern.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Autologous Platelet-rich Plasma Glue : Seroma and hematoma formations are the most common complications after plastic surgery. The aim of this study was to assess the efficacy of autologous platelet-rich plasma (A-PRP) glue to reduce postoperative wound complications and improve surgical outcomes.

http://otorhinolaryngology-crete.blogspot.com/2017/05/autologous-platelet-rich-plasma-glue.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Donor selection for ex vivo expanded natural killer cells as adoptive cancer immunotherapy

Future Oncology Ahead of Print.


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Novel translational therapeutic strategy by sequencing primary liver cancer genomes

Future Oncology Ahead of Print.


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Does physical activity improve survival and mortality among patients with different types of cancer?

Future Oncology Ahead of Print.


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The underestimated role of somatostatin analogs in the NETTER-1 trial

Future Oncology Ahead of Print.


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Venetoclax for the treatment of patients with chronic lymphocytic leukemia

Future Oncology Ahead of Print.


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via IFTTT

Donor selection for ex vivo expanded natural killer cells as adoptive cancer immunotherapy

Future Oncology Ahead of Print.


http://ift.tt/2r007kR

Novel translational therapeutic strategy by sequencing primary liver cancer genomes

Future Oncology Ahead of Print.


http://ift.tt/2pERfgn

Does physical activity improve survival and mortality among patients with different types of cancer?

Future Oncology Ahead of Print.


http://ift.tt/2qZZPdA

The underestimated role of somatostatin analogs in the NETTER-1 trial

Future Oncology Ahead of Print.


http://ift.tt/2pEZwRz

Venetoclax for the treatment of patients with chronic lymphocytic leukemia

Future Oncology Ahead of Print.


http://ift.tt/2qZEGQY

Donor selection for ex vivo expanded natural killer cells as adoptive cancer immunotherapy

Future Oncology Ahead of Print.


from Cancer via ola Kala on Inoreader http://ift.tt/2r007kR
via IFTTT

Novel translational therapeutic strategy by sequencing primary liver cancer genomes

Future Oncology Ahead of Print.


from Cancer via ola Kala on Inoreader http://ift.tt/2pERfgn
via IFTTT

Does physical activity improve survival and mortality among patients with different types of cancer?

Future Oncology Ahead of Print.


from Cancer via ola Kala on Inoreader http://ift.tt/2qZZPdA
via IFTTT

The underestimated role of somatostatin analogs in the NETTER-1 trial

Future Oncology Ahead of Print.


from Cancer via ola Kala on Inoreader http://ift.tt/2pEZwRz
via IFTTT

Venetoclax for the treatment of patients with chronic lymphocytic leukemia

Future Oncology Ahead of Print.


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Genome-wide analysis of somatic copy number alterations and chromosomal breakages in osteosarcoma

Abstract

Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. It is characterized by highly complex karyotypes with structural and numerical chromosomal alterations. The observed OS-specific characteristics in localization and frequencies of chromosomal breakages strongly implicate a specific set of responsible driver genes or a specific mechanism of fragility induction. In this study, a comprehensive assessment of somatic copy number alterations (SCNAs) was performed in 160 OS samples using whole-genome CytoScan High Density arrays (Affymetrix, Santa Clara, CA). Genes or regions frequently targeted by SCNAs were identified. Breakage analysis revealed OS specific unstable regions in which well-known OS tumor suppressor genes, including TP53, RB1, WWOX, DLG2, and LSAMP are located. Certain genomic features, such as transposable elements and non-B DNA-forming motifs were found to be significantly enriched in the vicinity of chromosomal breakage sites. A complex breakage pattern – chromothripsis – has been suggested as a widespread phenomenon in OS. It was further demonstrated that hyperploidy and in particular chromothripsis were strongly correlated with OS patient clinical outcome. The revealed OS-specific fragility pattern provides novel clues for understanding the biology of osteosarcoma. This article is protected by copyright. All rights reserved.

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Neuroendocrine carcinoma of the breast: a review of 126 cases in China

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Genome-wide analysis of somatic copy number alterations and chromosomal breakages in osteosarcoma

Abstract

Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. It is characterized by highly complex karyotypes with structural and numerical chromosomal alterations. The observed OS-specific characteristics in localization and frequencies of chromosomal breakages strongly implicate a specific set of responsible driver genes or a specific mechanism of fragility induction. In this study, a comprehensive assessment of somatic copy number alterations (SCNAs) was performed in 160 OS samples using whole-genome CytoScan High Density arrays (Affymetrix, Santa Clara, CA). Genes or regions frequently targeted by SCNAs were identified. Breakage analysis revealed OS specific unstable regions in which well-known OS tumor suppressor genes, including TP53, RB1, WWOX, DLG2, and LSAMP are located. Certain genomic features, such as transposable elements and non-B DNA-forming motifs were found to be significantly enriched in the vicinity of chromosomal breakage sites. A complex breakage pattern – chromothripsis – has been suggested as a widespread phenomenon in OS. It was further demonstrated that hyperploidy and in particular chromothripsis were strongly correlated with OS patient clinical outcome. The revealed OS-specific fragility pattern provides novel clues for understanding the biology of osteosarcoma. This article is protected by copyright. All rights reserved.

http://ift.tt/2pDSbRn

Neuroendocrine carcinoma of the breast: a review of 126 cases in China

http://ift.tt/2pEg2Bv

A novel concept for tumour targeting with radiation: Inverse dose-painting or targeting the “Low Drug Uptake Volume”

We tested a novel treatment approach combining (1) targeting radioresistant hypoxic tumour cells with the hypoxia-activated prodrug TH-302 and (2) inverse radiation dose-painting to boost selectively non-hypoxic tumour sub-volumes having no/low drug uptake.

http://ift.tt/2pDzX2E

Salvage radiation therapy after prostatectomy: Understanding the dose–response effect

We read with interest the paper recently published by King [1]: "The dose–response of salvage radiotherapy following radical prostatectomy: a systematic review and meta-analysis". The authors claimed the existence of a previously suggested dose–effect for salvage radiotherapy [2–4]; they tried to quantify it by fitting 3–6year biochemical relapse free survival (BRFs) data referred to about 10,000 patients from 71 publications. Despite the clear merit of the work, the predictive power of the simple sigmoid model suggested by King was poor, as shown by the large data spread in Fig.

http://ift.tt/2qZAwZ2

Cystic adventitial disease of the common femoral vein

We present the case of a 46-year-old commercial pilot with a history of unilateral leg swelling following a flight to Geneva. Although initial clinical examination suggested a deep vein thrombosis, the swelling only partially resolved with anticoagulation and further imaging suggested the presence of adventitial cystic disease (ACD). The patient underwent initial anticoagulation to allow any thrombus to be lysed, followed by excision of the ACD from the venous wall and venous reconstruction. Following the excision of the ACD, providing the patient remains asymptomatic and further imaging finds normal venous anatomy, we hope the patient will discontinue anticoagulation and return to flying.

http://ift.tt/2q9XlGT

Bilateral corneal injury after face-paint application to upper eyelids

A 40-year-old woman with no known medical conditions or allergies presented with severely painful, watery eyes and blurred vision. She reported topical application of face-paint onto both upper eyelids prior to attending a Halloween party. She subsequently noticed a burning sensation, epiphora and misty vision within a few hours. On examination, bilateral large corneal epithelial defects were highlighted with fluorescein dye under cobalt-blue light. Antibiotic ointment, mydriatic and sodium ascorbate 10% eye-drops were given, and patient was advised to keep the eyelids shut to promote healing. No corneal defects were visible by day 4 and the patient was discharged with vision recovering to normal levels.

http://ift.tt/2q7aC4R

Mixed cryoglobulinemia: a diagnostic and therapeutic challenge

Mixed cryoglobulinemia is frequently secondary to hepatitis C virus infection. Diagnosis and therapeutic management are challenging, depending on the spectrum and severity of manifestations, as well as on the presence of comorbidities. We describe a case of a 79-year-old woman with a non-cirrhotic hepatitis C virus infection presenting with weakness, arthralgias, purpuric rash with left leg ulcerative lesions, bilateral peripheral sensorimotor polyneuropathy, renal impairment and cardiac failure. The investigation was compatible with a severe type II mixed cryoglobulinemia with multisystemic involvement, including a low-grade B cell lymphoma and concomitant intestinal tuberculosis. Initial management with immunosuppressive therapy with glucocorticoids to control symptoms and simultaneous tuberculosis treatment was required. Unavailability of adequate antiviral treatment led to the need to control the severity of systemic manifestations with rituximab, before the effective aetiological treatment with sofosbuvir and ledipasvir was possible, allowing the definitive resolution of the disease.

http://ift.tt/2qaj29P

A rare view: giant liver abscess with underlying liver metastases

Description 

Liver abscess (LA) refers to a suppurated cavity caused by the invasion of liver parenchyma, most commonly by Gram-negative  bacteria. Although rare, it is potentially life-threatening. Giant LA (>10 cm) is even more uncommon.1 Symptoms and signs are non-specific and the diagnosis relies essentially on imaging with ultrasound (US) and CT scan. Treatment is based on antimicrobials, abscess drainage and approach to the underlying disease.2 For pyogenic LA, prompt initiation of empirical broad-spectrum intravenous antibiotics,2 usually a third-generation cephalosporin plus metronidazole, is essential with subsequent adjustment to culture and sensitivity, usually for 10–14 days, depending on clinical and radiological response. Together with CT scan or US-guided percutaneous catheter drainage (PD), it is the initial treatment of choice.1 However, large LA >5 cm predicts failure of PD and the need for surgical drainage.3 Malignancy and multiloculation are also risk factors for therapy...

http://ift.tt/2q7cCdo

Vitamin A deficiency due to chronic malabsorption: an ophthalmic manifestation of a systemic condition

A 47-year-old woman presented with a 4-week history of progressive loss of vision, first manifesting as night blindness. Additionally, the patient reported frequent severe episodes of diarrhoea over the past month. Her medical history included end-stage renal failure for which she was currently on haemodialysis after a failed renal transplant, chronic pancreatitis and autonomic diabetes mellitus. Ophthalmological examination revealed severe bilateral corneal xerosis, bilateral Bitot's spots and inferior ulceration of the right cornea. A diagnosis of xerophthalmia due to vitamin A deficiency was made, most likely due to the presence of small intestinal bacterial overgrowth and the patient's chronic malabsorptive state. Standard management using oral vitamin A tablets was ineffective, resulting in the patient requiring intravenous supplementation. The extent of visual deterioration on presentation and the difficulties encountered managing the patient resulted in the patient's vision failing to improve.

http://ift.tt/2qa5NWs

Role of Radiation Therapy in the Treatment of Hodgkin Lymphoma

Abstract

Radiation therapy has historically been the pillar of curative treatment for Hodgkin lymphoma (HL). With improved efficacy of systemic therapy and the ever-increasing recognition of treatment-related morbidity in long-term survivors, the role of radiotherapy has evolved significantly. Modern combined modality therapy (CMT) with multi-agent chemotherapy followed by involved site radiation therapy (ISRT) to initially involved sites of disease remains the gold standard for the majority of patients with HL. Reduction of long-term treatment-related toxicity has become the major driver in clinical trial design for early-stage HL while improved disease-specific survival remains the goal in patients with more advanced and unfavorable disease. This review will address the data supporting the use of radiotherapy in HL as well as specific methods for reducing late toxicity from radiotherapy.

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Role of Radiation Therapy in the Treatment of Hodgkin Lymphoma

Abstract

Radiation therapy has historically been the pillar of curative treatment for Hodgkin lymphoma (HL). With improved efficacy of systemic therapy and the ever-increasing recognition of treatment-related morbidity in long-term survivors, the role of radiotherapy has evolved significantly. Modern combined modality therapy (CMT) with multi-agent chemotherapy followed by involved site radiation therapy (ISRT) to initially involved sites of disease remains the gold standard for the majority of patients with HL. Reduction of long-term treatment-related toxicity has become the major driver in clinical trial design for early-stage HL while improved disease-specific survival remains the goal in patients with more advanced and unfavorable disease. This review will address the data supporting the use of radiotherapy in HL as well as specific methods for reducing late toxicity from radiotherapy.

http://ift.tt/2pq80Qk

Controversies in Postoperative Irradiation of Oropharyngeal Cancer After Transoral Surgery

Publication date: Available online 11 May 2017
Source:Surgical Oncology Clinics of North America
Author(s): Sue S. Yom, Jon Mallen-St. Clair, Patrick K. Ha

Teaser

Transoral surgery (TOS) is a novel technology whose adoption is expanding in the United States and other countries. TOS offers the possibility of a minimally invasive surgical approach to head and neck cancers. Its most frequent application has been in oropharyngeal cancers (OPC), of which most are associated with human papillomavirus (HPV). For HPV-associated OPC, where high response and survival rates are expected, deintensification of standard therapy is a major area of clinical research. In HPV-OPC, traditional pathologic risk factors indicating a need for adjuvant radiation or chemoradiation may not apply as strongly.


http://ift.tt/2pEwt0g

Optimal Use of Combined Modality Therapy in the Treatment of Esophageal Cancer

Publication date: Available online 11 May 2017
Source:Surgical Oncology Clinics of North America
Author(s): Talha Shaikh, Joshua E. Meyer, Eric M. Horwitz

Teaser

Esophageal cancer is associated with a poor prognosis with 5-year survival rates of approximately 15% to 20%. Although patients with early stage disease may adequately be treated with a single modality, combined therapy typically consisting of neoadjuvant chemoradiation followed by esophagectomy is being adopted increasingly in patients with locally advanced disease. In patients who are not surgical candidates, definitive chemoradiation is the preferred treatment approach. All patients with newly diagnosed esophageal cancer should be evaluated in the multidisciplinary setting by a surgeon, radiation oncologist, and medical oncologist owing to the importance of each specialty in the management of these patients.


http://ift.tt/2q8G5Dv

The Role of Radiation Therapy for Pancreatic Cancer in the Adjuvant and Neoadjuvant Settings

Publication date: Available online 11 May 2017
Source:Surgical Oncology Clinics of North America
Author(s): Shahed N. Badiyan, Jason K. Molitoris, Michael D. Chuong, William F. Regine, Adeel Kaiser

Teaser

Pancreatic cancer is the third leading cause of cancer-related death in the United States. Although surgery remains the only curative treatment, chemotherapy and radiation therapy are frequently used. In the adjuvant setting, radiation is usually delivered with chemotherapy to eradicate residual microscopic or macroscopic disease in the resection bed. Neoadjuvant radiation therapy has become more frequently utilized. This article reviews the historical and modern literature regarding radiation therapy in the neoadjuvant and adjuvant settings, focusing on the evolution of radiation therapy techniques and clinical trials in an attempt to identify patients best suited to receiving radiation therapy.


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Update on Radiotherapy for Central Nervous System Malignancies

Publication date: Available online 11 May 2017
Source:Surgical Oncology Clinics of North America
Author(s): Eric Kemmerer, Sunjay Shah

Teaser

Malignancies arising from the central nervous system are rare. Brain metastases, in contrast, are perhaps the most common neurologic complication of cancer. Radiotherapy, as part of combined modality therapy, continues to evolve with the advancement of stereotactic radiosurgery indications; addition of new technologies, such as alternating electric field therapy; and mounting advances in the complex biology of these entities. The explosion of new clinical trials combined with newly discovered molecular markers suggest the beginning of a paradigm shift in the management of these challenging malignancies that will allow for future risk-stratification strategies.


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Novel Opportunities to Use Radiation Therapy with Immune Checkpoint Inhibitors for Melanoma Management

Publication date: Available online 11 May 2017
Source:Surgical Oncology Clinics of North America
Author(s): Kamran A. Ahmed, Sungjune Kim, Louis B. Harrison

Teaser

Immunotherapy has revolutionized the systemic management of numerous malignancies. Nowhere has the proven benefit of these agents in clinical practice been more evident than in the management of advanced melanoma. Numerous preclinical studies have revealed the potential benefit of immune-priming radiotherapy in stimulating tumor-specific immune responses. This signal for immune activation may lead to clinically relevant synergy with immune checkpoint inhibitors against malignant cells. In this review, the authors summarize the current data outlining the role radiation therapy may play in the management of advanced melanoma alongside immune checkpoint inhibitors.


http://ift.tt/2pEv7me

Brachytherapy in the Management of Prostate Cancer

Publication date: Available online 11 May 2017
Source:Surgical Oncology Clinics of North America
Author(s): Bradley J. Stish, Brian J. Davis, Lance A. Mynderse, Christopher L. Deufel, Richard Choo

Teaser

Brachytherapy is performed by directly inserting radioactive sources into the prostate gland and is an important treatment option for appropriately selected men with prostate adenocarcinoma. Brachytherapy provides highly conformal radiotherapy and delivers tumoricidal doses that exceed those administered with external beam radiation therapy. There is a significant body of literature supporting the excellent long-term oncologic and safety outcomes achieved when brachytherapy is used for men in all risk categories of nonmetastatic prostate cancer. This article highlights some important considerations and published outcomes that relate to brachytherapy and its role in the treatment of prostate cancer.


http://ift.tt/2q8v7O2

Radiotherapy for Anal Cancer

Publication date: Available online 11 May 2017
Source:Surgical Oncology Clinics of North America
Author(s): Serguei A. Castaneda, Lindsay B. Romak

Teaser

The treatment of anal cancer has evolved remarkably in the past 30 years. Definitive chemoradiotherapy is the standard of care, allowing organ preservation and maintenance of continence for most patients. This article reviews recent advances in radiotherapy planning and delivery that have resulted in improvements in treatment-related toxicity. Most notably, the advent and wide adoption of intensity-modulated radiotherapy provides a superior toxicity profile compared with older techniques, while maintaining similar oncologic outcomes. Current areas of active research include optimizing and individualizing treatment intensity and possible integration of biologic agents and immunotherapies in the treatment of anal cancer.


http://ift.tt/2pElGTP

Updates in the Treatment of Breast Cancer with Radiotherapy

Publication date: Available online 11 May 2017
Source:Surgical Oncology Clinics of North America
Author(s): Serguei A. Castaneda, Jon Strasser

Teaser

Breast-conserving therapy is one of the most remarkable achievements of modern cancer care. The authors review the evidence supporting the role of adjuvant radiotherapy as the standard of care for breast cancer after breast-conserving surgery, consensus guidelines for margins in invasive cancer disease and ductal carcinoma in situ, the role of partial-breast irradiation and hypofractionated whole-breast irradiation, and the evolving indications for postmastectomy radiation therapy and extent of nodal coverage. Areas of research include specific methods of partial-breast irradiation, interactions between neoadjuvant chemotherapy and radiotherapy, and integration of molecular profiles with the selection of the best treatment modality and timing.


http://ift.tt/2q8ftT8

Impact of iron deficiency anemia on CD4 and CD8-T lymphocytes among preschool-school children

Abstract

Iron is a basic element at cellular and molecular levels for proper development and effective function of the immune system. Children with iron deficiency are more susceptible to infections and have many alterations to their immune profile. The current study investigates the quantitative changes for CD4 and CD8 T-lymphocytes among symptomatic and asymptomatic iron deficient children. Flow cytometry using conjugated monoclonal antibodies was used for assessment of the CD4 and CD8 T-lymphocyte subsets among 30 asymptomatic iron deficient children, 28 iron deficiency anemia (IDA) symptomatic children, and 30 healthy children. A significant decline of CD4+ lymphocyte percentage was observed among both asymptomatic and symptomatic iron deficient children when compared to the control group. The percentage of CD8+ lymphocytes increased among both iron deficient groups. The current study concludes that symptomatic and asymptomatic iron deficient children have an alteration of CD4 and CD8 cell ratios. Early diagnosis and treatment of asymptomatic iron deficiency are mandatory to prevent functional deterioration of cell-mediated immunity.

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The effect of pressure-controlled inverse ratio ventilation on lung protection in obese patients undergoing gynecological laparoscopic surgery

Abstract

Specific aim

To examine the effects of pressure-controlled inverse ratio ventilation (PCIRV) and volume-control ventilation (VCV) on arterial oxygenation, pulmonary function, hemodynamics, levels of surfactant protein A (SP-A), and tumor necrosis factor-α (TNF-α) in obese patients undergoing gynecological laparoscopic surgery.

Methods

Sixty patients, body mass index (BMI) ≥30 kg/m², scheduled for elective gynecological laparoscopic surgery were enrolled in the study. Patients were randomly allocated to receive either PCIRV with an inspiratory–expiratory (I:E) ratio of 1.5:1 (PCIRV group n = 30) or VCV with an I:E ratio of 1:2 (VCV group n = 30). Ventilation variables, viz. tidal volume (V _T), dynamic respiratory-system compliance (C _RS), driving pressure (ΔP = V _T/C _RS), arterial blood oxygen partial pressure/fraction of inspiration oxygen (PaO₂/FiO₂) and arterial blood carbon dioxide partial pressure (PaCO₂), were measured. Hemodynamic variables, viz. mean arterial pressure (MAP), heart rate (HR), and serum levels of SP-A and TNF-α, were also measured.

Results

When compared to patients in the VCV group, patients in the PCIRV group had higher V _T, dynamic C_RS, and PaO₂/FiO₂, and lower ΔP and PaCO₂ at 20 and 60 min after the start of pneumoperitoneum (p < 0.05). Patients in the PCIRV group had lower SP-A and TNF-α levels at 24 and 48 h after surgery than those in the VCV group (p < 0.05).

Conclusion

In obese patients undergoing gynecological laparoscopic surgery, PCIRV can improve ventilation, promote gas exchange and oxygenation, and is associated with decreased levels of SP-A and TNF-α. These effects demonstrate improved lung protection provided by PCIRV in this patient population.

http://ift.tt/2pDpvbg

Intratumoral Injection of HSV1716, an Oncolytic Herpes Virus, Is Safe and Shows Evidence of Immune Response and Viral Replication in Young Cancer Patients

Purpose: HSV1716 is an oncolytic herpes simplex virus-1 (HSV-1) studied in adults via injection into the brain and superficial tumors. To determine the safety of administering HSV1716 to pediatric patients with cancer, we conducted a phase I trial of image-guided injection in young patients with relapsed or refractory extracranial cancers.

Experimental Design: We delivered a single dose of 10⁵ to 10⁷ infectious units of HSV1716 via computed tomography–guided intratumoral injection and measured tumor responses by imaging. Patients were eligible for up to three more doses if they achieved stable disease. We monitored HSV-1 serum titers and shedding by PCR and culture.

Results: We administered a single dose of HSV1716 to eight patients and two doses to one patient. We did not observe any dose-limiting toxicities. Adverse events attributed to virus included low-grade fever, chills, and mild cytopenias. Six of eight HSV-1 seronegative patients at baseline showed seroconversion on day 28. Six of nine patients had detectable HSV-1 genomes by PCR in peripheral blood appearing on day +4 consistent with de novo virus replication. Two patients had transient focal increases in metabolic activity on ¹⁸fluorine-deoxyglucose PET, consistent with inflammatory reactions. In one case, the same geographic region that flared later appeared necrotic on imaging. No patient had an objective response to HSV1716.

Conclusions: Intratumoral HSV1716 is safe and well-tolerated without shedding in children and young adults with late-stage, aggressive cancer. Viremia consistent with virus replication and transient inflammatory reactions hold promise for future HSV1716 studies. Clin Cancer Res; 1–9. ©2017 AACR.

http://ift.tt/2ppRVKJ

Intratumoral Injection of HSV1716, an Oncolytic Herpes Virus, Is Safe and Shows Evidence of Immune Response and Viral Replication in Young Cancer Patients

Purpose: HSV1716 is an oncolytic herpes simplex virus-1 (HSV-1) studied in adults via injection into the brain and superficial tumors. To determine the safety of administering HSV1716 to pediatric patients with cancer, we conducted a phase I trial of image-guided injection in young patients with relapsed or refractory extracranial cancers.

Experimental Design: We delivered a single dose of 10⁵ to 10⁷ infectious units of HSV1716 via computed tomography–guided intratumoral injection and measured tumor responses by imaging. Patients were eligible for up to three more doses if they achieved stable disease. We monitored HSV-1 serum titers and shedding by PCR and culture.

Results: We administered a single dose of HSV1716 to eight patients and two doses to one patient. We did not observe any dose-limiting toxicities. Adverse events attributed to virus included low-grade fever, chills, and mild cytopenias. Six of eight HSV-1 seronegative patients at baseline showed seroconversion on day 28. Six of nine patients had detectable HSV-1 genomes by PCR in peripheral blood appearing on day +4 consistent with de novo virus replication. Two patients had transient focal increases in metabolic activity on ¹⁸fluorine-deoxyglucose PET, consistent with inflammatory reactions. In one case, the same geographic region that flared later appeared necrotic on imaging. No patient had an objective response to HSV1716.

Conclusions: Intratumoral HSV1716 is safe and well-tolerated without shedding in children and young adults with late-stage, aggressive cancer. Viremia consistent with virus replication and transient inflammatory reactions hold promise for future HSV1716 studies. Clin Cancer Res; 1–9. ©2017 AACR.

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Blocking of stromal interaction molecule 1 expression influence cell proliferation and promote cell apoptosis in vitro and inhibit tumor growth in vivo in head and neck squamous cell carcinoma

by Ping Li, Xue-yan Bian, Qing Chen, Xiao-feng Yao, Xu-dong Wang, Wen-chao Zhang, Ying-jie Tao, Rui Jin, Lun Zhang

Calcium signal plays an important role in a variety of cancer cell metabolism, but knowledge on its role in head and neck squamous cell carcinoma (HNSCC) is limited. Store-operated calcium entry (SOCE) is the principal Ca²⁺ entry mechanism that maintains calcium concentration and produces calcium signal in non-excitable cells. SOCE is triggered by stromal interaction molecule 1 (STIM1), which is located in endoplasmic reticulum (ER) as Ca²⁺ sensor. Although, many studies demonstrated that STIM1 and SOCE play important functions in the regulation of many cancer progressions, their clinical relevance in HNSCC remains unclear. In this study, STIM1 expression levels notably increased in 89% HNSCC tissues compared with those in adjacent normal tissues. Meanwhile, this overexpression was close associated with tumor size but not with neck lymph node metastasis. Thus, this study mainly focuses on STIM1 function in HNSCC tumor growth. Three HNSCC cell lines, namely, TSCCA (oral cancer cell line) and Hep2 (laryngeal cell line) with high STIM1 expression levels and Tb3.1 (oral cancer cell line) with STIM1 expression level lower than previous two cell lines, were selected for in vitro study. Downregulated STIM1 expression levels in TSCCA and Hep2 arrested cells in G0/G1 stages, promoted cell apoptosis, and inhibited cell proliferation. By contrast, upregulated STIM1 expression in Tb3.1 inhibited cell apoptosis and promoted cell proliferation. Induced by thapsigargin (TG), ER stress was amplified when STIM1 expression was downregulated but was attenuated as STIM1 expression was upregulated. Furthermore, TSCCA cell xenograft models confirmed that STIM1 could promote HNSCC tumor growth in vivo. The present study provides new insight into HNSCC molecular mechanism and potential therapeutic target through targeting SOCE-dependent process. However, whether STIM1 participates in HNSCC metastasis requires further study.

http://ift.tt/2r6FtN3

European interpretation of North American Post Mastectomy Radiotherapy Guideline Update

Publication date: Available online 10 May 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): I.H. Kunkler, J.M. Dixon, M. Maclennan, N.S. Russell




http://ift.tt/2q6IDlV

Blocking of stromal interaction molecule 1 expression influence cell proliferation and promote cell apoptosis in vitro and inhibit tumor growth in vivo in head and neck squamous cell carcinoma

by Ping Li, Xue-yan Bian, Qing Chen, Xiao-feng Yao, Xu-dong Wang, Wen-chao Zhang, Ying-jie Tao, Rui Jin, Lun Zhang

Calcium signal plays an important role in a variety of cancer cell metabolism, but knowledge on its role in head and neck squamous cell carcinoma (HNSCC) is limited. Store-operated calcium entry (SOCE) is the principal Ca²⁺ entry mechanism that maintains calcium concentration and produces calcium signal in non-excitable cells. SOCE is triggered by stromal interaction molecule 1 (STIM1), which is located in endoplasmic reticulum (ER) as Ca²⁺ sensor. Although, many studies demonstrated that STIM1 and SOCE play important functions in the regulation of many cancer progressions, their clinical relevance in HNSCC remains unclear. In this study, STIM1 expression levels notably increased in 89% HNSCC tissues compared with those in adjacent normal tissues. Meanwhile, this overexpression was close associated with tumor size but not with neck lymph node metastasis. Thus, this study mainly focuses on STIM1 function in HNSCC tumor growth. Three HNSCC cell lines, namely, TSCCA (oral cancer cell line) and Hep2 (laryngeal cell line) with high STIM1 expression levels and Tb3.1 (oral cancer cell line) with STIM1 expression level lower than previous two cell lines, were selected for in vitro study. Downregulated STIM1 expression levels in TSCCA and Hep2 arrested cells in G0/G1 stages, promoted cell apoptosis, and inhibited cell proliferation. By contrast, upregulated STIM1 expression in Tb3.1 inhibited cell apoptosis and promoted cell proliferation. Induced by thapsigargin (TG), ER stress was amplified when STIM1 expression was downregulated but was attenuated as STIM1 expression was upregulated. Furthermore, TSCCA cell xenograft models confirmed that STIM1 could promote HNSCC tumor growth in vivo. The present study provides new insight into HNSCC molecular mechanism and potential therapeutic target through targeting SOCE-dependent process. However, whether STIM1 participates in HNSCC metastasis requires further study.

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Cancer, radiothérapie et système immunitaire

Publication date: Available online 10 May 2017
Source:Cancer/Radiothérapie
Author(s): J.P. Nesseler, D. Peiffert, G. Vogin, P. Nickers
De nouveaux concepts se distinguent aujourd'hui en cancérologie. Les traitements systémiques sont plus efficaces et plus variés, l'espérance de vie s'allonge en phase métastatique avec émergence de la maladie oligométastatique. La radiothérapie stéréotaxique à fortes doses par fraction se développe et représente une nouvelle arme permettant d'assurer le contrôle tumoral local. La sphère de la radiobiologie s'est élargie avec intégration du microenvironnement tumoral au sein duquel les médiateurs de l'inflammation et les cellules immunitaires jouent un rôle majeur après une irradiation. Les inhibiteurs des checkpoints de l'immunité connaissent un fort développement. Ainsi, l'immunité antitumorale connaît un formidable renouveau et semble impliquée dans l'effet abscopal observé après irradiation, notamment en cas d'association radiothérapie et inhibiteurs des checkpoints, comme l'ont montré de nombreuses études précliniques et plusieurs essais cliniques précoces. Paradoxalement, l'irradiation génère également des effets immunosuppresseurs. Cette revue a pour objectif de faire le point sur les effets antagonistes de l'irradiation sur l'immunité antitumorale, d'exposer certaines données concernant les associations de radiothérapie et d'inhibiteurs des checkpoints de l'immunité et soulever certaines inconnues ouvrant de nouveaux travaux de recherche.Novel paradigms emerge in oncology today. Systemic treatments are more effective and diversified along with an increased life expectancy in oligometastatic patients. Stereotactic radiotherapy using hypofractionation opens new perspectives for local tumour control. The area of radiobiology has expanded with integration of tumour microenvironment in which radiation-induced inflammation mediators and immune system play a major role. Immunity checkpoints inhibitors experience a major development. This rapidly evolving field seems involved in the abscopal effects, especially when radiation is combined with checkpoints inhibitors, as demonstrated in numerous preclinical studies and several clinical trials. Paradoxically, irradiation also produces immunosuppressive effects. This manuscript aims to report the dual effects of ionizing radiation on the immune system and reviews some results of the combination of radiation and immunity chekpoints inhibitors and also research perspectives.



http://ift.tt/2pDbBps

Cancer, radiothérapie et système immunitaire

Publication date: Available online 10 May 2017
Source:Cancer/Radiothérapie
Author(s): J.P. Nesseler, D. Peiffert, G. Vogin, P. Nickers
De nouveaux concepts se distinguent aujourd'hui en cancérologie. Les traitements systémiques sont plus efficaces et plus variés, l'espérance de vie s'allonge en phase métastatique avec émergence de la maladie oligométastatique. La radiothérapie stéréotaxique à fortes doses par fraction se développe et représente une nouvelle arme permettant d'assurer le contrôle tumoral local. La sphère de la radiobiologie s'est élargie avec intégration du microenvironnement tumoral au sein duquel les médiateurs de l'inflammation et les cellules immunitaires jouent un rôle majeur après une irradiation. Les inhibiteurs des checkpoints de l'immunité connaissent un fort développement. Ainsi, l'immunité antitumorale connaît un formidable renouveau et semble impliquée dans l'effet abscopal observé après irradiation, notamment en cas d'association radiothérapie et inhibiteurs des checkpoints, comme l'ont montré de nombreuses études précliniques et plusieurs essais cliniques précoces. Paradoxalement, l'irradiation génère également des effets immunosuppresseurs. Cette revue a pour objectif de faire le point sur les effets antagonistes de l'irradiation sur l'immunité antitumorale, d'exposer certaines données concernant les associations de radiothérapie et d'inhibiteurs des checkpoints de l'immunité et soulever certaines inconnues ouvrant de nouveaux travaux de recherche.Novel paradigms emerge in oncology today. Systemic treatments are more effective and diversified along with an increased life expectancy in oligometastatic patients. Stereotactic radiotherapy using hypofractionation opens new perspectives for local tumour control. The area of radiobiology has expanded with integration of tumour microenvironment in which radiation-induced inflammation mediators and immune system play a major role. Immunity checkpoints inhibitors experience a major development. This rapidly evolving field seems involved in the abscopal effects, especially when radiation is combined with checkpoints inhibitors, as demonstrated in numerous preclinical studies and several clinical trials. Paradoxically, irradiation also produces immunosuppressive effects. This manuscript aims to report the dual effects of ionizing radiation on the immune system and reviews some results of the combination of radiation and immunity chekpoints inhibitors and also research perspectives.



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HN1 contributes to migration, invasion, and tumorigenesis of breast cancer by enhancing MYC activity

Abstract

Background

Hematological and neurological expressed 1 (HN1) is upregulated in many tumors, but the role of HN1 in breast cancer progression and its regulatory mechanism have not been well understood.

Methods

To study the role of HN1 in the initiation and progression of breast cancer, we examined HN1 levels in breast cancer cells and tissues and analyzed the relationship between HN1 levels and patient survival. We used mammosphere formation assay, side population analysis, wound healing assay, transwell assay, soft agar formation assay, and xenografted tumor model to determine the effect of HN1 on the expansion of breast cancer stem cells, and the migration, invasion and tumorigenesis of breast cancer. To determine whether HN1 regulates MYC, we used quantitative real-time PCR and Western blot analysis to assess the expression of MYC and their targeted genes to determine the phenotype caused by knockdown of MYC in breast cancer cell with HN1 overexpression.

Results

In this study, we found that HN1 was upregulated in breast cancer tissues. Patients with high levels of HN1 expression had significantly shorter survival than those with low HN1 expression. In breast cancer cell line, ectopic overexpression of HN1 not only promoted the expansion of breast cancer stem cells, but also promoted cell migration, invasion, and tumorigenesis, while knockdown of HN1 reduced these effects. Furthermore, there was a positive correlation between MYC (also known as c-MYC) level and HN1 level, mechanism analysis suggested HN1 promoted the expression of MYC and its targeted genes like CDK4, CCND1, p21, CAV1, and SFRP1. Downregulation of MYC abrogated the effect of HN1 overexpression in breast cancer cell lines.

Conclusion

Taken together, these data reveal that HN1 promotes the progression of breast cancer by upregulating MYC expression, and might be a therapeutic target for breast cancer.

from Cancer via ola Kala on Inoreader http://ift.tt/2q9JJeJ
via IFTTT

HN1 contributes to migration, invasion, and tumorigenesis of breast cancer by enhancing MYC activity

Abstract

Background

Hematological and neurological expressed 1 (HN1) is upregulated in many tumors, but the role of HN1 in breast cancer progression and its regulatory mechanism have not been well understood.

Methods

To study the role of HN1 in the initiation and progression of breast cancer, we examined HN1 levels in breast cancer cells and tissues and analyzed the relationship between HN1 levels and patient survival. We used mammosphere formation assay, side population analysis, wound healing assay, transwell assay, soft agar formation assay, and xenografted tumor model to determine the effect of HN1 on the expansion of breast cancer stem cells, and the migration, invasion and tumorigenesis of breast cancer. To determine whether HN1 regulates MYC, we used quantitative real-time PCR and Western blot analysis to assess the expression of MYC and their targeted genes to determine the phenotype caused by knockdown of MYC in breast cancer cell with HN1 overexpression.

Results

In this study, we found that HN1 was upregulated in breast cancer tissues. Patients with high levels of HN1 expression had significantly shorter survival than those with low HN1 expression. In breast cancer cell line, ectopic overexpression of HN1 not only promoted the expansion of breast cancer stem cells, but also promoted cell migration, invasion, and tumorigenesis, while knockdown of HN1 reduced these effects. Furthermore, there was a positive correlation between MYC (also known as c-MYC) level and HN1 level, mechanism analysis suggested HN1 promoted the expression of MYC and its targeted genes like CDK4, CCND1, p21, CAV1, and SFRP1. Downregulation of MYC abrogated the effect of HN1 overexpression in breast cancer cell lines.

Conclusion

Taken together, these data reveal that HN1 promotes the progression of breast cancer by upregulating MYC expression, and might be a therapeutic target for breast cancer.

http://ift.tt/2q9JJeJ

The performance of the mSEPT9 assay is influenced by algorithm, cancer stage and age, but not sex and cancer location

Abstract

Purpose

This study aims to examine the influence of algorithm and subject-related factors, including cancer stage, age, sex, and cancer location, on the performance of the SEPT9 gene methylation test, an assay approved by the US FDA for colorectal cancer (CRC) screening.

Methods

A total of 1225 subjects were recruited in this opportunistic screening study, including 388 CRC patients, 139 subjects with adenoma, 108 subjects with hyperplastic polyps, and 590 subjects with no evidence of disease (NED). Epi proColon 2.0 CE assay was used to examine the blood level of SEPT9 gene methylation.

Results

It was found that tests using 1/3 algorithm exhibited higher detection rate than those using the 2/3 algorithm for CRC, adenoma, hyperplastic polyps, while the false positive rate in subjects with NED was also higher with 1/3 algorithm. The positive detection rate (PDR) of the assay for stage 0 and I CRC were lower than later stages (Stage II, III and IV). Interestingly, the normal subjects above 60 years old exhibited significantly higher PDR than subjects from younger groups, while no significant change in PDR was observed among age groups in CRC patients. Furthermore, no difference in the PDR for CRC was found between male and female, and the PDR for CRC at various colorectal locations were essentially identical.

Conclusions

Algorithm, cancer stage and age are factors affecting the detection rate of the SEPT9 assay, while sex and cancer location appeared to have no influence on its performance.

http://ift.tt/2pCMgMD

Clinical impact of sarcopenia and relevance of nutritional intake in patients before and after allogeneic hematopoietic stem cell transplantation

Abstract

Purpose

We conducted a retrospective study to evaluate the effect of rehabilitation on minimizing sarcopenia during hematopoietic stem cell transplantation (HSCT) therapy.

Methods

We developed a protocol to test for retention of physical function during HSCT. Muscle strength, muscle circumference, and muscle function before and after HSCT were measured. Consecutive patients with hematological malignancies who underwent HSCT treatment were recruited in this research.

Results

We included 34 patients (16 females, 18 males; median age, 51.5 years). Bodyweight significantly decreased after HSCT (p < 0.001). Nine females and three males had sarcopenia prior to allogeneic HSCT. After HSCT, bilateral hand grip strength and bilateral knee extensor strength decreased significantly. The total caloric intakes for pre-conditioning, during preparation regimen, and after transplant were 1709, 1024, and 1445 kcal, respectively, and were significantly attenuated in the post-transplant period. Serum albumin was significantly decreased in the final period. Conversely, C-reactive protein was slightly but significantly increased across the transplantation process. Multivariate regression analysis revealed that oral caloric intake after the transplantation period and sex were significantly related to muscle weakness (p = 0.033 and 0.036, respectively).

Conclusions

Sarcopenia during HSCT was affected by oral caloric intake during the preparation regimen and after transplantation. Physical therapy in conjunction with nutritional therapy may help prevent weakness in HSCT recipients.

http://ift.tt/2qYC6um

Updated results from GEST study: a randomized, three-arm phase III study for advanced pancreatic cancer

Abstract

Purpose

The GEST study showed non-inferiority of S-1 but not superiority of gemcitabine plus S-1 (GS) to gemcitabine alone for overall survival with the data by the cut-off date of 31st July in 2010 for chemo-naïve patients with advanced pancreatic cancer. We considered it important to determine whether S-1 maintains non-inferiority after a long-term follow-up in the GEST study and to obtain a firm positive conclusion. In addition, it may be an interesting challenge to explore the efficacious profile of GS in the long-term follow-up study. Using the data from the follow-up period, background and efficacy in patients from Taiwan and Japan, as well as the rates of tumor shrinkage in locally advanced and metastatic patients (Waterfall plot) were also analyzed.

Methods

The results of the primary analysis were reconfirmed, and subset analysis of overall survival and progression-free survival was performed based on the overall survival data updated by the cut-off date of 31st July in 2011.

Results

The median follow-up period was 29.8 months, and 795 deaths occurred (95.6%). The median overall survival was 8.8 months for gemcitabine, 9.7 months for S-1 (hazard ratio [HR], 0.96; 97.5% confidence interval [CI], 0.79–1.17), and 9.9 months for GS (HR 0.91; 97.5% CI 0.75–1.11). In patients with performance status (PS) 0, the median overall survival was 9.8 months for gemcitabine, 10.9 months for S-1, and 10.5 months for GS. In patients with PS 1, the median overall survival was 6.2 months for gemcitabine, 6.3 months for S-1, and 9.6 months for GS.

Conclusion

Our survey reconfirmed the non-inferiority of S-1 to gemcitabine and showed S-1 can be used as one of the standard treatment options for advanced pancreatic cancer.

Trial registration

ClinicalTrials.gov: NCT00498225.

http://ift.tt/2pDbUR4

Impact of denosumab use on the survival of untreated non-squamous non-small cell lung cancer patients with bone metastases

Abstract

Purpose

Denosumab reduces the incidence of skeletal-related events (SREs) in solid tumor patients with bone metastases (BM). However, there have been no detailed reports of the efficacy of denosumab in untreated non-squamous non-small cell lung cancer (NSCLC) patients with BM.

Methods

The medical records of patients with untreated non-squamous NSCLC and BM at diagnosis at our institution were reviewed retrospectively. The overall survival (OS) and the time to SREs were analyzed according to the treatment for the BM.

Results

Of the total of 149 patients who were eligible, 52 had received denosumab (Dmab group), 51 had received zoledronic acid (ZA group), and 46 had received no treatment (No-Tx group) for the BM. The frequencies of prior SREs were higher in the Dmab group and ZA group than in the No-Tx group (44, 41 and 22%, respectively); however, there were no significant differences in any of the other clinicopathological characteristics examined among the three groups. The median OS in the Dmab group, ZA group and No-Tx group were 21.4 months, 12.7 months and 10.5 months, respectively; the OS was significantly longer in the Dmab group than in the ZA group (P < 0.01). Results of multivariate analysis revealed that denosumab treatment was significantly associated with a more favorable survival [hazard ratio, 0.500; 95% CI 0.332–0.741; P < 0.01]. No significant difference in the time to SREs was observed among the three groups.

Conclusions

Our results suggest that treatment with denosumab may improve the overall survival of non-squamous NSCLC patients with BM.

http://ift.tt/2qYYaoF

The presence of cancerous nodules in lymph nodes is a novel indicator of distant metastasis and poor survival in patients with papillary thyroid carcinoma

Abstract

Purpose

Several characteristics of lymph node metastasis (LNM) as predictors of the risk of recurrence or death were examined in patients with papillary thyroid carcinoma (PTC). The presence of cancerous nodules as a characteristic of LNMs in PTC has not yet been reported. The objective of this study was to evaluate the use of the cancerous nodules in the lymph node (CNLN) to determine the risk of distant metastasis and survival in patients with PTC.

Methods

This retrospective observational cohort study enrolled 1408 patients with pathologically confirmed PTC without initial distant metastasis who underwent thyroidectomy and neck dissection. All patients were divided into two groups (CNLN group and Non-CNLN group) according to the presence of CNLN.

Results

Multivariate analyses showed that the presence of a special histologic variant (OR 3.31), CNLN (OR 7.13), and lateral LNM (OR 4.02) was an independent factor predictive of distant metastasis. Distant metastasis was found in 23.1% and 2.3% of patients in the CNLN and Non-CNLN group, respectively (p < 0.001). Furthermore, tumor-specific death was found in 7.7% and 0.6% of patients in the CNLN and Non-CNLN group, respectively (p < 0.001). Patients in the CNLN group had a shorter distant metastasis-free survival and overall survival than patients in the Non-CNLN group (p < 0.001).

Conclusions

The presence of CNLN in patients with PTC is a novel indicator of distant metastasis and poor survival. PTC patients accompanied with CNLN should undergo more aggressive treatment and careful follow-up.

http://ift.tt/2pCEpyq

Ferritin heavy chain as a molecular imaging reporter gene in glioma xenografts

Abstract

Purpose

The development of glioma therapy in clinical practice (e.g., gene therapy) calls for efficiently visualizing and tracking glioma cells in vivo. Human ferritin heavy chain is a novel gene reporter in magnetic resonance imaging. This study proposes hFTH as a reporter gene for MR molecular imaging in glioma xenografts.

Methods

Rat C6 glioma cells were infected by packaged lentivirus carrying hFTH and EGFP genes and obtained by fluorescence-activated cell sorting. The iron-loaded ability was analyzed by the total iron reagent kit. Glioma nude mouse models were established subcutaneously and intracranially. Then, in vivo tumor bioluminescence was performed via the IVIS spectrum imaging system. The MR imaging analysis was analyzed on a 7T animal MRI scanner. Finally, the expression of hFTH was analyzed by western blotting and histological analysis.

Results

Stable glioma cells carrying hFTH and EGFP reporter genes were successfully obtained. The intracellular iron concentration was increased without impairing the cell proliferation rate. Glioma cells overexpressing hFTH showed significantly decreased signal intensity on T₂-weighted MRI both in vitro and in vivo. EGFP fluorescent imaging could also be detected in the subcutaneous and intracranial glioma xenografts. Moreover, the expression of the transferritin receptor was significantly increased in glioma cells carrying the hFTH reporter gene.

Conclusion

Our study illustrated that hFTH generated cellular MR imaging contrast efficiently in glioma via regulating the expression of transferritin receptor. This might be a useful reporter gene in cell tracking and MR molecular imaging for glioma diagnosis, gene therapy and tumor metastasis.

http://ift.tt/2qYY5kR

The performance of the mSEPT9 assay is influenced by algorithm, cancer stage and age, but not sex and cancer location

Abstract

Purpose

This study aims to examine the influence of algorithm and subject-related factors, including cancer stage, age, sex, and cancer location, on the performance of the SEPT9 gene methylation test, an assay approved by the US FDA for colorectal cancer (CRC) screening.

Methods

A total of 1225 subjects were recruited in this opportunistic screening study, including 388 CRC patients, 139 subjects with adenoma, 108 subjects with hyperplastic polyps, and 590 subjects with no evidence of disease (NED). Epi proColon 2.0 CE assay was used to examine the blood level of SEPT9 gene methylation.

Results

It was found that tests using 1/3 algorithm exhibited higher detection rate than those using the 2/3 algorithm for CRC, adenoma, hyperplastic polyps, while the false positive rate in subjects with NED was also higher with 1/3 algorithm. The positive detection rate (PDR) of the assay for stage 0 and I CRC were lower than later stages (Stage II, III and IV). Interestingly, the normal subjects above 60 years old exhibited significantly higher PDR than subjects from younger groups, while no significant change in PDR was observed among age groups in CRC patients. Furthermore, no difference in the PDR for CRC was found between male and female, and the PDR for CRC at various colorectal locations were essentially identical.

Conclusions

Algorithm, cancer stage and age are factors affecting the detection rate of the SEPT9 assay, while sex and cancer location appeared to have no influence on its performance.

from Cancer via ola Kala on Inoreader http://ift.tt/2pCMgMD
via IFTTT

Clinical impact of sarcopenia and relevance of nutritional intake in patients before and after allogeneic hematopoietic stem cell transplantation

Abstract

Purpose

We conducted a retrospective study to evaluate the effect of rehabilitation on minimizing sarcopenia during hematopoietic stem cell transplantation (HSCT) therapy.

Methods

We developed a protocol to test for retention of physical function during HSCT. Muscle strength, muscle circumference, and muscle function before and after HSCT were measured. Consecutive patients with hematological malignancies who underwent HSCT treatment were recruited in this research.

Results

We included 34 patients (16 females, 18 males; median age, 51.5 years). Bodyweight significantly decreased after HSCT (p < 0.001). Nine females and three males had sarcopenia prior to allogeneic HSCT. After HSCT, bilateral hand grip strength and bilateral knee extensor strength decreased significantly. The total caloric intakes for pre-conditioning, during preparation regimen, and after transplant were 1709, 1024, and 1445 kcal, respectively, and were significantly attenuated in the post-transplant period. Serum albumin was significantly decreased in the final period. Conversely, C-reactive protein was slightly but significantly increased across the transplantation process. Multivariate regression analysis revealed that oral caloric intake after the transplantation period and sex were significantly related to muscle weakness (p = 0.033 and 0.036, respectively).

Conclusions

Sarcopenia during HSCT was affected by oral caloric intake during the preparation regimen and after transplantation. Physical therapy in conjunction with nutritional therapy may help prevent weakness in HSCT recipients.

from Cancer via ola Kala on Inoreader http://ift.tt/2qYC6um
via IFTTT

Updated results from GEST study: a randomized, three-arm phase III study for advanced pancreatic cancer

Abstract

Purpose

The GEST study showed non-inferiority of S-1 but not superiority of gemcitabine plus S-1 (GS) to gemcitabine alone for overall survival with the data by the cut-off date of 31st July in 2010 for chemo-naïve patients with advanced pancreatic cancer. We considered it important to determine whether S-1 maintains non-inferiority after a long-term follow-up in the GEST study and to obtain a firm positive conclusion. In addition, it may be an interesting challenge to explore the efficacious profile of GS in the long-term follow-up study. Using the data from the follow-up period, background and efficacy in patients from Taiwan and Japan, as well as the rates of tumor shrinkage in locally advanced and metastatic patients (Waterfall plot) were also analyzed.

Methods

The results of the primary analysis were reconfirmed, and subset analysis of overall survival and progression-free survival was performed based on the overall survival data updated by the cut-off date of 31st July in 2011.

Results

The median follow-up period was 29.8 months, and 795 deaths occurred (95.6%). The median overall survival was 8.8 months for gemcitabine, 9.7 months for S-1 (hazard ratio [HR], 0.96; 97.5% confidence interval [CI], 0.79–1.17), and 9.9 months for GS (HR 0.91; 97.5% CI 0.75–1.11). In patients with performance status (PS) 0, the median overall survival was 9.8 months for gemcitabine, 10.9 months for S-1, and 10.5 months for GS. In patients with PS 1, the median overall survival was 6.2 months for gemcitabine, 6.3 months for S-1, and 9.6 months for GS.

Conclusion

Our survey reconfirmed the non-inferiority of S-1 to gemcitabine and showed S-1 can be used as one of the standard treatment options for advanced pancreatic cancer.

Trial registration

ClinicalTrials.gov: NCT00498225.

from Cancer via ola Kala on Inoreader http://ift.tt/2pDbUR4
via IFTTT

Impact of denosumab use on the survival of untreated non-squamous non-small cell lung cancer patients with bone metastases

Abstract

Purpose

Denosumab reduces the incidence of skeletal-related events (SREs) in solid tumor patients with bone metastases (BM). However, there have been no detailed reports of the efficacy of denosumab in untreated non-squamous non-small cell lung cancer (NSCLC) patients with BM.

Methods

The medical records of patients with untreated non-squamous NSCLC and BM at diagnosis at our institution were reviewed retrospectively. The overall survival (OS) and the time to SREs were analyzed according to the treatment for the BM.

Results

Of the total of 149 patients who were eligible, 52 had received denosumab (Dmab group), 51 had received zoledronic acid (ZA group), and 46 had received no treatment (No-Tx group) for the BM. The frequencies of prior SREs were higher in the Dmab group and ZA group than in the No-Tx group (44, 41 and 22%, respectively); however, there were no significant differences in any of the other clinicopathological characteristics examined among the three groups. The median OS in the Dmab group, ZA group and No-Tx group were 21.4 months, 12.7 months and 10.5 months, respectively; the OS was significantly longer in the Dmab group than in the ZA group (P < 0.01). Results of multivariate analysis revealed that denosumab treatment was significantly associated with a more favorable survival [hazard ratio, 0.500; 95% CI 0.332–0.741; P < 0.01]. No significant difference in the time to SREs was observed among the three groups.

Conclusions

Our results suggest that treatment with denosumab may improve the overall survival of non-squamous NSCLC patients with BM.

from Cancer via ola Kala on Inoreader http://ift.tt/2qYYaoF
via IFTTT

The presence of cancerous nodules in lymph nodes is a novel indicator of distant metastasis and poor survival in patients with papillary thyroid carcinoma

Abstract

Purpose

Several characteristics of lymph node metastasis (LNM) as predictors of the risk of recurrence or death were examined in patients with papillary thyroid carcinoma (PTC). The presence of cancerous nodules as a characteristic of LNMs in PTC has not yet been reported. The objective of this study was to evaluate the use of the cancerous nodules in the lymph node (CNLN) to determine the risk of distant metastasis and survival in patients with PTC.

Methods

This retrospective observational cohort study enrolled 1408 patients with pathologically confirmed PTC without initial distant metastasis who underwent thyroidectomy and neck dissection. All patients were divided into two groups (CNLN group and Non-CNLN group) according to the presence of CNLN.

Results

Multivariate analyses showed that the presence of a special histologic variant (OR 3.31), CNLN (OR 7.13), and lateral LNM (OR 4.02) was an independent factor predictive of distant metastasis. Distant metastasis was found in 23.1% and 2.3% of patients in the CNLN and Non-CNLN group, respectively (p < 0.001). Furthermore, tumor-specific death was found in 7.7% and 0.6% of patients in the CNLN and Non-CNLN group, respectively (p < 0.001). Patients in the CNLN group had a shorter distant metastasis-free survival and overall survival than patients in the Non-CNLN group (p < 0.001).

Conclusions

The presence of CNLN in patients with PTC is a novel indicator of distant metastasis and poor survival. PTC patients accompanied with CNLN should undergo more aggressive treatment and careful follow-up.

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Ferritin heavy chain as a molecular imaging reporter gene in glioma xenografts

Abstract

Purpose

The development of glioma therapy in clinical practice (e.g., gene therapy) calls for efficiently visualizing and tracking glioma cells in vivo. Human ferritin heavy chain is a novel gene reporter in magnetic resonance imaging. This study proposes hFTH as a reporter gene for MR molecular imaging in glioma xenografts.

Methods

Rat C6 glioma cells were infected by packaged lentivirus carrying hFTH and EGFP genes and obtained by fluorescence-activated cell sorting. The iron-loaded ability was analyzed by the total iron reagent kit. Glioma nude mouse models were established subcutaneously and intracranially. Then, in vivo tumor bioluminescence was performed via the IVIS spectrum imaging system. The MR imaging analysis was analyzed on a 7T animal MRI scanner. Finally, the expression of hFTH was analyzed by western blotting and histological analysis.

Results

Stable glioma cells carrying hFTH and EGFP reporter genes were successfully obtained. The intracellular iron concentration was increased without impairing the cell proliferation rate. Glioma cells overexpressing hFTH showed significantly decreased signal intensity on T₂-weighted MRI both in vitro and in vivo. EGFP fluorescent imaging could also be detected in the subcutaneous and intracranial glioma xenografts. Moreover, the expression of the transferritin receptor was significantly increased in glioma cells carrying the hFTH reporter gene.

Conclusion

Our study illustrated that hFTH generated cellular MR imaging contrast efficiently in glioma via regulating the expression of transferritin receptor. This might be a useful reporter gene in cell tracking and MR molecular imaging for glioma diagnosis, gene therapy and tumor metastasis.

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Neuroendocrine carcinoma of the breast: a review of 126 cases in China

http://ift.tt/2r6LJnO

Neuroendocrine carcinoma of the breast: a review of 126 cases in China

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Perkins P, Cooksley CD and Cox JD. Breast cancer: Is ethnicity an independent prognostic factor for survival? Cancer. 1996;78:1241-1247.

http://ift.tt/2q7TbAG

Biodegradable seeds of holmium don’t change neurological function after implant in brain of rats

Publication date: July–August 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 4
Author(s): Mirla Fiuza Diniz, Diogo Milioli Ferreira, Wanderson Geraldo de Lima, Maria Lucia Pedrosa, Marcelo Eustáquio Silva, Stanley de Almeida Araujo, Kinulpe Honorato Sampaio, Tarcisio Passos Ribeiro de Campos, Savio Lana Siqueira
AimTo evaluate the surgical procedure and parenchymal abnormalities related to implantation of ceramic seeds with holmium-165 in rats' brain.BackgroundAn effective method of cancer treatment is brachytherapy in which radioactive seeds are implanted in the tumor, generating a high local dose of ionizing radiation that can eliminate tumor cells while protecting the surrounding healthy tissue. Biodegradable Ho¹⁶⁶-ceramic-seeds have been addressed recently.Methods and materialsThe experiments in this study were approved by the Ethics Committee on Animal Use at the Federal University of Ouro Preto, protocol number 2012/034. Twenty-one adult Fischer rats were divided into Naive Group, Sham Group and Group for seed implants (ISH). Surgical procedures for implantation of biodegradable seeds were done and 30 days after the implant radiographic examination and biopsy of the brain were performed. Neurological assays were also accomplished to exclude any injury resulting from either surgery or implantation of the seeds.ResultsRadiographic examination confirmed the location of the seeds in the brain. Neurological assays showed animals with regular spontaneous activity. The histological analysis showed an increase of inflammatory cells in the brain of the ISH group. Electron microscopy evidenced cytoplasmic organelles to be unchanged. Biochemical analyzes indicate there was neither oxidative stress nor oxidative damage in the ISH brain. CAT activity showed no difference between the groups as well as lipid peroxidation measured by TBARS.ConclusionsThe analysis of the data pointed out that the performed procedure is safe as no animal showed alterations of the neurological parameters and the seeds did not promote histological architectural changes in the brain tissue.



http://ift.tt/2q6JanU

Editorial board

Publication date: May–June 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 3





http://ift.tt/2q9BRK2

Cancer subtypes in aetiological research

Abstract

Researchers often attempt to categorize tumors into more homogeneous subtypes to better predict prognosis or understand pathogenic mechanisms. In clinical research, typically the focus is on prognosis: the tumor subtypes are intended to be associated with specific responses to treatment and/or different clinical outcomes. In aetiological research, the focus is on identifying distinct pathogenic mechanisms, which may involve different risk factors. We used directed acyclic graphs to present a framework for considering potential biases arising in aetiological research of tumor subtypes, when there is incomplete correspondence between the identified subtypes and the underlying pathogenic mechanisms. We identified two main scenarios: (1) weak effect, when the tumor subtypes are identified through combinations of characteristics and some of these characteristics are affected by factors that are unrelated with the underlying pathogenic mechanisms; and (2) lack of causality, when the set of characteristics corresponds with a mechanism that is actually not a cause of the tumor of interest. Examples of the magnitude of bias that can be introduced in these situations are provided. Although categorization of tumors into homogenous subtypes may have important implications for aetiological research and identification of risk factors, the characteristics used to classify tumors into subtypes should be as close as possible to the actual pathogenic mechanisms to avoid interpretative biases. Whenever our knowledge of these mechanisms is limited, research into risk factors for tumor subtypes should first aim to causally link the characteristics to the pathogenic mechanisms.

http://ift.tt/2q7QUFS

Intralesional interleukin-2 for unresectable mucosal melanoma refractory to nivolumab

http://ift.tt/2q6EPB3

Current status of chimeric antigen receptor engineered T cell-based and immune checkpoint blockade-based cancer immunotherapies

Abstract

Adoptive cell therapies with chimeric antigen receptor (CAR) engineered T cells (CAR-T) and immune checkpoint inhibition (ICI)-based cancer immunotherapies have lately shown remarkable success in certain tumor types. CAR-T cell-based therapies targeting CD19 can now induce durable remissions as well as prolong disease-free survival of patients with CD19 positive treatment refractory B cell malignancies and ICI-based therapies with humanized monoclonal antibodies against the T cell inhibitory receptors CTLA-4 and PD-1 as well as against the PD-1 ligand, PD-L1, can now achieve durable remissions as well as prolongation of life of a sizeable fraction of patients with melanoma and Hodgkin's lymphoma and non-small cell cancers. Most importantly, these immuno-therapeutic treatment modalities have raised the possibility of achieving long-term "containment" as well as "cures" for certain types of cancer. While this represents major advances in cancer immunotherapy, both modalities come with considerable toxicities, including fatalities. Although more work will be needed to bring CAR-T cell-based therapies to the bedside for most major cancers and a good deal more will be needed to make ICI—alone or in combination with other treatment modalities—work more consistently and across most major cancers, these two treatment modalities stand out as superb examples of successful translation of bench research to the bedside as well as represent real progress in the field of cancer immunotherapy.

http://ift.tt/2q9V7as

When trust is threatened: qualitative study of parents’ perspectives on problematic clinical relationships in child cancer care

Abstract

Objective

We explored parents' accounts of the parent-clinician relationship in childhood cancer to understand how parents who perceive threats to the relationship can be supported.

Methods

Multi-centre longitudinal qualitative study, with 67 UK parents of children (aged 1-12 years) receiving treatment for acute lymphoblastic leukaemia. Analyses drew on the wider sample but focussed on 50 semi-structured interviews with 20 parents and were informed by constant comparison.

Results

All 20 parents described problems with clinical care such as inadequate information or mistakes by staff, but varied in how much the problems threatened their sense of relationship with clinicians. Some parents saw the problems as having no relevance to the parent-clinician relationship. Others saw the problems as threats to the clinical relationship, but worked to "contain" the threat in ways that preserved a trusting relationship with at least one senior clinician. Parents' containment work protected the security they needed from the parent-clinician relationship, but containment was a tenuous process for some. A few parents were unable to contain the problems at all; lacking trust in clinicians, these parents suffered considerably.

Conclusions

Given the complexity of childhood cancer care, problems with clinical care are inevitable. By engaging in containment work, parents met their needs to feel secure in the face of these problems, but the extent to which parents should have to do this work is debatable. Parents could benefit from support to seek help when problems arise which threaten their trust in clinicians. Attachment theory can guide clinicians in giving this support.

http://ift.tt/2pCEpOX

Validation of the prognostic value of new sub-stages within the AJCC 8th edition of non-small cell lung cancer

Abstract

Background

The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for non-small cell lung cancer (NSCLC) has been released. The current study tried to validate the prognostic significance of the new system among patients registered within the surveillance, epidemiology and end results (SEER) database.

Methods

SEER database (2010–2013) has been accessed through SEER*Stat program and AJCC 8th edition stages were reconstructed utilizing the collaborative stage descriptions. Overall and lung cancer-specific survival analyses according to both 7th and 8th editions were conducted through Kaplan–Meier analysis and multivariate analysis was conducted through a Cox proportional hazard model.

Results

A total of 127,096 patients with NSCLC were identified in the period from 2010 to 2013. For overall survival assessment according to the 8th edition, P values for all pair-wise comparisons among different stages were significant (<0.0001) except for the comparisons between stage IB and IIA (P = 0.146); stage IIA and IIB (P = 0.165). For lung cancer-specific survival according to the 8th edition, P values for all pair-wise comparisons among different stages were significant (<0.001). Among patients with stage I disease, multivariate analysis for factors affecting overall and lung cancer-specific survival among patients with stage I disease was conducted. The following factors were associated with worse overall and lung cancer-specific survival: age ≥70 years, more advanced stage, male gender, squamous histology, no surgery and no radiotherapy (P < 0.0001 for all factors).

Conclusion

This SEER analysis supports the prognostic significance of the added sub-stages described within AJCC 8th edition stages I and III. Further work is needed to incorporate molecular markers and personalize the future editions of the AJCC staging system.

http://ift.tt/2q7Z2pD

Validation of SDM-Q-Doc Questionnaire to measure shared decision-making physician’s perspective in oncology practice

Abstract

Objective

The aim of this study was to analyze the psychometric properties of the Shared Decision-Making Questionnaire–Physician version (SDM-Q-Doc) in a sample of medical oncologists who provide adjuvant treatment to patients with non-metastatic resected cancer and the correlations between the total SDM-Q-Doc score and physician satisfaction with the information provided.

Methods

Prospective, observational and multicenter study in which 32 medical oncologists and 520 patients were recruited. The psychometric properties, dimensionality, and factor structure of the SDM-Q-Doc were assessed.

Results

Exploratory factor analyses suggested that the most likely solution was two-dimensional, with two correlated factors: one factor regarding information and another one about treatment. Confirmatory factor analysis based on cross-validation showed that the fitted two-dimensional solution provided the best fit to the data. Reliability analyses revealed good accuracy for the derived scores, both total and sub-scale, with estimates ranging from 0.81 to 0.89. The results revealed significant correlations between the total SDM-Q-Doc score and physician satisfaction with the information provided (p < 0.01); between information sub-scale scores (factor 1) and satisfaction (p < 0.01), and between treatment sub-scale scores (factor 2) and satisfaction (p < 0.01). Medical oncologists of older age and those with more years of experience showed more interest in the patient preferences (p = 0.026 and p = 0.020, respectively). Patient age negatively correlated with SDM information (p < 0.01) and physicians appear to provide more information to young patients.

Conclusion

SDM-Q-Doc showed good psychometric properties and could be a helpful tool that examines physician's perspective of SDM and as an indicator of quality and satisfaction in patients with cancer.

http://ift.tt/2pDRV5A

Utility of urinary circulating tumor DNA for EGFR mutation detection in different stages of non-small cell lung cancer patients

Abstract

Purpose

Non-invasive methods of molecular profiling for non-small cell lung cancer (NSCLC) are useful for monitoring disease progression. The aim of the current study was to ascertain if transrenal DNA is sensitive for clinical correlation and EGFR detection in NSCLC patients.

Methods

160 patients at various stages of the disease participated and samples were collected prospectively at 2-month intervals. A baseline sample was taken before treatment commencement. To ascertain the sensitivity of transrenal DNA, we compared its results with plasma DNA. ddPCR was used to profile the urine and blood samples for key EGFR mutations.

Results

Using tumor tissues as references, our study showed good concordance in EGFR mutations with transrenal DNA before treatment. Results were highly matching in late-stage NSCLC patients, with stage III/IV patients yielding an agreement of more than 90%. The assay was also sensitive to detect early-stage patients after surgical procedures. Profiles were highly concordant with results derived from plasma DNA, demonstrating the specificity of transrenal DNA assays. Serial monitoring of these patients showed stable molecular signatures and correlated to different treatments. Survival analysis showed good prognostic utility for late-stage patients with high transrenal DNA variations and patients that acquired T790M mutation.

Conclusion

The study demonstrated the feasibility of using transrenal DNA in mutation profiling for different stages of NSCLC patients. It highlights the importance of continual monitoring and has potential clinical utility in the clinical management of NSCLC.

http://ift.tt/2q7UT5n

Validation of the prognostic value of new sub-stages within the AJCC 8th edition of non-small cell lung cancer

Abstract

Background

The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for non-small cell lung cancer (NSCLC) has been released. The current study tried to validate the prognostic significance of the new system among patients registered within the surveillance, epidemiology and end results (SEER) database.

Methods

SEER database (2010–2013) has been accessed through SEER*Stat program and AJCC 8th edition stages were reconstructed utilizing the collaborative stage descriptions. Overall and lung cancer-specific survival analyses according to both 7th and 8th editions were conducted through Kaplan–Meier analysis and multivariate analysis was conducted through a Cox proportional hazard model.

Results

A total of 127,096 patients with NSCLC were identified in the period from 2010 to 2013. For overall survival assessment according to the 8th edition, P values for all pair-wise comparisons among different stages were significant (<0.0001) except for the comparisons between stage IB and IIA (P = 0.146); stage IIA and IIB (P = 0.165). For lung cancer-specific survival according to the 8th edition, P values for all pair-wise comparisons among different stages were significant (<0.001). Among patients with stage I disease, multivariate analysis for factors affecting overall and lung cancer-specific survival among patients with stage I disease was conducted. The following factors were associated with worse overall and lung cancer-specific survival: age ≥70 years, more advanced stage, male gender, squamous histology, no surgery and no radiotherapy (P < 0.0001 for all factors).

Conclusion

This SEER analysis supports the prognostic significance of the added sub-stages described within AJCC 8th edition stages I and III. Further work is needed to incorporate molecular markers and personalize the future editions of the AJCC staging system.

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via IFTTT

Validation of SDM-Q-Doc Questionnaire to measure shared decision-making physician’s perspective in oncology practice

Abstract

Objective

The aim of this study was to analyze the psychometric properties of the Shared Decision-Making Questionnaire–Physician version (SDM-Q-Doc) in a sample of medical oncologists who provide adjuvant treatment to patients with non-metastatic resected cancer and the correlations between the total SDM-Q-Doc score and physician satisfaction with the information provided.

Methods

Prospective, observational and multicenter study in which 32 medical oncologists and 520 patients were recruited. The psychometric properties, dimensionality, and factor structure of the SDM-Q-Doc were assessed.

Results

Exploratory factor analyses suggested that the most likely solution was two-dimensional, with two correlated factors: one factor regarding information and another one about treatment. Confirmatory factor analysis based on cross-validation showed that the fitted two-dimensional solution provided the best fit to the data. Reliability analyses revealed good accuracy for the derived scores, both total and sub-scale, with estimates ranging from 0.81 to 0.89. The results revealed significant correlations between the total SDM-Q-Doc score and physician satisfaction with the information provided (p < 0.01); between information sub-scale scores (factor 1) and satisfaction (p < 0.01), and between treatment sub-scale scores (factor 2) and satisfaction (p < 0.01). Medical oncologists of older age and those with more years of experience showed more interest in the patient preferences (p = 0.026 and p = 0.020, respectively). Patient age negatively correlated with SDM information (p < 0.01) and physicians appear to provide more information to young patients.

Conclusion

SDM-Q-Doc showed good psychometric properties and could be a helpful tool that examines physician's perspective of SDM and as an indicator of quality and satisfaction in patients with cancer.

from Cancer via ola Kala on Inoreader http://ift.tt/2pDRV5A
via IFTTT

Utility of urinary circulating tumor DNA for EGFR mutation detection in different stages of non-small cell lung cancer patients

Abstract

Purpose

Non-invasive methods of molecular profiling for non-small cell lung cancer (NSCLC) are useful for monitoring disease progression. The aim of the current study was to ascertain if transrenal DNA is sensitive for clinical correlation and EGFR detection in NSCLC patients.

Methods

160 patients at various stages of the disease participated and samples were collected prospectively at 2-month intervals. A baseline sample was taken before treatment commencement. To ascertain the sensitivity of transrenal DNA, we compared its results with plasma DNA. ddPCR was used to profile the urine and blood samples for key EGFR mutations.

Results

Using tumor tissues as references, our study showed good concordance in EGFR mutations with transrenal DNA before treatment. Results were highly matching in late-stage NSCLC patients, with stage III/IV patients yielding an agreement of more than 90%. The assay was also sensitive to detect early-stage patients after surgical procedures. Profiles were highly concordant with results derived from plasma DNA, demonstrating the specificity of transrenal DNA assays. Serial monitoring of these patients showed stable molecular signatures and correlated to different treatments. Survival analysis showed good prognostic utility for late-stage patients with high transrenal DNA variations and patients that acquired T790M mutation.

Conclusion

The study demonstrated the feasibility of using transrenal DNA in mutation profiling for different stages of NSCLC patients. It highlights the importance of continual monitoring and has potential clinical utility in the clinical management of NSCLC.

from Cancer via ola Kala on Inoreader http://ift.tt/2q7UT5n
via IFTTT

Validation of the prognostic value of new sub-stages within the AJCC 8th edition of non-small cell lung cancer

Abstract

Background

The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for non-small cell lung cancer (NSCLC) has been released. The current study tried to validate the prognostic significance of the new system among patients registered within the surveillance, epidemiology and end results (SEER) database.

Methods

SEER database (2010–2013) has been accessed through SEER*Stat program and AJCC 8th edition stages were reconstructed utilizing the collaborative stage descriptions. Overall and lung cancer-specific survival analyses according to both 7th and 8th editions were conducted through Kaplan–Meier analysis and multivariate analysis was conducted through a Cox proportional hazard model.

Results

A total of 127,096 patients with NSCLC were identified in the period from 2010 to 2013. For overall survival assessment according to the 8th edition, P values for all pair-wise comparisons among different stages were significant (<0.0001) except for the comparisons between stage IB and IIA (P = 0.146); stage IIA and IIB (P = 0.165). For lung cancer-specific survival according to the 8th edition, P values for all pair-wise comparisons among different stages were significant (<0.001). Among patients with stage I disease, multivariate analysis for factors affecting overall and lung cancer-specific survival among patients with stage I disease was conducted. The following factors were associated with worse overall and lung cancer-specific survival: age ≥70 years, more advanced stage, male gender, squamous histology, no surgery and no radiotherapy (P < 0.0001 for all factors).

Conclusion

This SEER analysis supports the prognostic significance of the added sub-stages described within AJCC 8th edition stages I and III. Further work is needed to incorporate molecular markers and personalize the future editions of the AJCC staging system.

http://ift.tt/2q7Z2pD

Validation of SDM-Q-Doc Questionnaire to measure shared decision-making physician’s perspective in oncology practice

Abstract

Objective

The aim of this study was to analyze the psychometric properties of the Shared Decision-Making Questionnaire–Physician version (SDM-Q-Doc) in a sample of medical oncologists who provide adjuvant treatment to patients with non-metastatic resected cancer and the correlations between the total SDM-Q-Doc score and physician satisfaction with the information provided.

Methods

Prospective, observational and multicenter study in which 32 medical oncologists and 520 patients were recruited. The psychometric properties, dimensionality, and factor structure of the SDM-Q-Doc were assessed.

Results

Exploratory factor analyses suggested that the most likely solution was two-dimensional, with two correlated factors: one factor regarding information and another one about treatment. Confirmatory factor analysis based on cross-validation showed that the fitted two-dimensional solution provided the best fit to the data. Reliability analyses revealed good accuracy for the derived scores, both total and sub-scale, with estimates ranging from 0.81 to 0.89. The results revealed significant correlations between the total SDM-Q-Doc score and physician satisfaction with the information provided (p < 0.01); between information sub-scale scores (factor 1) and satisfaction (p < 0.01), and between treatment sub-scale scores (factor 2) and satisfaction (p < 0.01). Medical oncologists of older age and those with more years of experience showed more interest in the patient preferences (p = 0.026 and p = 0.020, respectively). Patient age negatively correlated with SDM information (p < 0.01) and physicians appear to provide more information to young patients.

Conclusion

SDM-Q-Doc showed good psychometric properties and could be a helpful tool that examines physician's perspective of SDM and as an indicator of quality and satisfaction in patients with cancer.

http://ift.tt/2pDRV5A

Utility of urinary circulating tumor DNA for EGFR mutation detection in different stages of non-small cell lung cancer patients

Abstract

Purpose

Non-invasive methods of molecular profiling for non-small cell lung cancer (NSCLC) are useful for monitoring disease progression. The aim of the current study was to ascertain if transrenal DNA is sensitive for clinical correlation and EGFR detection in NSCLC patients.

Methods

160 patients at various stages of the disease participated and samples were collected prospectively at 2-month intervals. A baseline sample was taken before treatment commencement. To ascertain the sensitivity of transrenal DNA, we compared its results with plasma DNA. ddPCR was used to profile the urine and blood samples for key EGFR mutations.

Results

Using tumor tissues as references, our study showed good concordance in EGFR mutations with transrenal DNA before treatment. Results were highly matching in late-stage NSCLC patients, with stage III/IV patients yielding an agreement of more than 90%. The assay was also sensitive to detect early-stage patients after surgical procedures. Profiles were highly concordant with results derived from plasma DNA, demonstrating the specificity of transrenal DNA assays. Serial monitoring of these patients showed stable molecular signatures and correlated to different treatments. Survival analysis showed good prognostic utility for late-stage patients with high transrenal DNA variations and patients that acquired T790M mutation.

Conclusion

The study demonstrated the feasibility of using transrenal DNA in mutation profiling for different stages of NSCLC patients. It highlights the importance of continual monitoring and has potential clinical utility in the clinical management of NSCLC.

http://ift.tt/2q7UT5n

Intralesional interleukin-2 for unresectable mucosal melanoma refractory to nivolumab

http://ift.tt/2q6EPB3

Current status of chimeric antigen receptor engineered T cell-based and immune checkpoint blockade-based cancer immunotherapies

Abstract

Adoptive cell therapies with chimeric antigen receptor (CAR) engineered T cells (CAR-T) and immune checkpoint inhibition (ICI)-based cancer immunotherapies have lately shown remarkable success in certain tumor types. CAR-T cell-based therapies targeting CD19 can now induce durable remissions as well as prolong disease-free survival of patients with CD19 positive treatment refractory B cell malignancies and ICI-based therapies with humanized monoclonal antibodies against the T cell inhibitory receptors CTLA-4 and PD-1 as well as against the PD-1 ligand, PD-L1, can now achieve durable remissions as well as prolongation of life of a sizeable fraction of patients with melanoma and Hodgkin's lymphoma and non-small cell cancers. Most importantly, these immuno-therapeutic treatment modalities have raised the possibility of achieving long-term "containment" as well as "cures" for certain types of cancer. While this represents major advances in cancer immunotherapy, both modalities come with considerable toxicities, including fatalities. Although more work will be needed to bring CAR-T cell-based therapies to the bedside for most major cancers and a good deal more will be needed to make ICI—alone or in combination with other treatment modalities—work more consistently and across most major cancers, these two treatment modalities stand out as superb examples of successful translation of bench research to the bedside as well as represent real progress in the field of cancer immunotherapy.

http://ift.tt/2q9V7as

Accelerating drug development by efficiently using emerging PK/PD data from an adaptable entry-into-human trial: example of lumretuzumab

Abstract

Purpose

This study aimed at evaluating if pharmacokinetic and pharmacodynamic data from the first few patients treated with an investigational monoclonal antibody in a dose-escalation study can be used to guide the early initiation of potentially more efficacious combination regimens.

Methods

Emerging pharmacokinetic and pharmacodynamic data from the first nine patients treated with lumretuzumab (a glycoengineered anti-HER3 monoclonal antibody) monotherapy at doses from 100 to 400 mg q2w were used along with a pharmacokinetic model that incorporated target-mediated drug disposition to guide the selection of the starting dose for use in combination regimens.

Results

The dose-escalation study investigated lumretuzumab doses up to 2000 mg q2w and a maximum tolerated dose was not reached. However, the model described in this report predicted linear lumretuzumab pharmacokinetics and >95% target saturation at doses ≥400 mg q2w. These data, along with safety data, contributed to the decision to begin dose-escalation studies in combination with cetuximab and erlotinib using a starting dose of 400 mg lumretuzumab. Pharmacokinetic data from patients treated with lumretuzumab 400–2000 mg q2w in combination regimens were consistent with the model predictions.

Conclusion

PK/PD modelling of emerging clinical data might accelerate development programs by enabling additional parts of a trial to commence before completion of the monotherapy part. The dose and schedule of lumretuzumab were optimised for concomitant therapy at doses substantially below the highest dose investigated.

http://ift.tt/2qXHZaY