Cancer frequently associates with the occurrence of cachexia, a debilitating syndrome responsible for reduced tolerance to anticancer therapies, as well as increased morbidity and mortality. Dr. Bonetto's group reported that animals bearing cancers not only show reduced skeletal muscle mass and strength, but also dramatic bone loss, despite the absence of bone metastases. Their latest findings revealed that muscle and bone depletion may also occur as a direct consequence of anticancer treatments (i.e., chemotherapy). There is now substantial agreement on the fact that abnormalities of the so-called ‘muscle-bone crosstalk’ may contribute to the onset of cachexia secondary to cancer or chemotherapy. Clinical and experimental observations also suggest that pharmacological bone preservation may concurrently benefit muscle mass in animal models, burn patients and osteoporotic women.
In this webinar Dr. Bonetto will present evidence that bone preservation directly impacts muscle size and function in cachexia, thus also contributing to unraveling novel pathogenetic mechanisms and opening new avenues for treatment.
Lorlatinib shows efficacy in treating ALK-positive and ROS1-positive non-small cell lung cancer (NSCLC) in patients who have failed earlier treatments. In a study of 200 NSCLC patients treated with lorlatinib, the disease control rate was 86% for ALK-positive patients and 88% for ROS1-positive patients. Lorlatinib also achieved high response rates in central nervous system metastases of 41.7% for ALK-positive patients and 53.3% for ROS1-positive patients. Median progression-free survival was 11.8 months for ALK-positive patients and 7.6 months for ROS1-positive patients. Lorlatinib demonstrated clinical benefit in treating advanced AL
Osteoarthritis is a degenerative joint disease characterized by the breakdown of cartilage. It most commonly affects weight-bearing joints like the hips and knees. The cartilage, bone, synovial membrane, capsule, ligaments and muscles are all affected as the disease progresses. Symptoms include joint pain and stiffness that worsens with use of the affected joint. Treatment focuses on reducing pain and inflammation, maintaining joint mobility, and may include joint replacement surgery for severe cases.
This document summarizes treatment approaches for metastatic castration-resistant prostate cancer (mCRPC). It discusses definitions of CRPC and mechanisms of resistance. For mCRPC patients with PSADT >10 months and no symptoms, secondary hormonal therapies are recommended, while those with PSADT <10 months receive second-generation antiandrogens. Docetaxel remains first-line for symptomatic mCRPC, while abiraterone, enzalutamide, radium-223, and sipuleucel-T are also options. Detection of AR-V7 in circulating tumor cells may help determine if taxanes or AR-targeted therapies are most suitable. Ongoing treatment, monitoring of
Rheumatoid arthritis is a chronic autoimmune disease that causes inflammation and damage to joints. It affects around 1-3% of the global population. While its exact causes are unknown, genetic and environmental factors are believed to play a role. Key symptoms include tender, warm, swollen joints and morning stiffness lasting over an hour. Diagnosis is based on criteria such as the number and location of affected joints, presence of rheumatoid factor or anti-CCP antibodies, and response to treatment. Treatment aims to control symptoms, prevent further joint damage, and improve quality of life using medications such as methotrexate, sulfasalazine, biologics that target cytokines, and newer drugs like tofacitinib. The
Chair & Presenter, David R. Jones, MD, and Nathan A. Pennell, MD, PhD, FASCO, prepared useful Practice Aids pertaining to NSCLC for this CME/MOC activity titled “Adjuvant EGFR-Targeted Therapy as a Game Changer: How to Implement New Standards of Care in Multimodal Management of Stage I-III EGFR-Mutated NSCLC.” For the full presentation, downloadable Practice Aids, and complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/3mFfjji. CME/MOC credit will be available until December 2, 2022.
Each year, approximately 14 million people around the globe are diagnosed with cancer. About a third of cancer deaths can be prevented, which is why cancer awareness is so important. Different types of cancers are honored throughout the year so you can be aware of when each cancer awareness month is and which colored ribbon is used to represent it. We’ve compiled all current cancer awareness months and their appropriate ribbon colors into one easy-to-use chart. Cancer is a disease that can affect anyone at any time, and our infographic helps to spread awareness so that other people can be aware of the signs, symptoms, and risk factors for cancer. Awareness saves lives! View the full infographic at http://www.wheelsforwishes.org/cancer-awareness-ribbons/.
- The document summarizes key landmark clinical trials investigating treatments for metastatic gastric cancer.
- The ToGA trial found that adding trastuzumab (Herceptin) to standard chemotherapy (cisplatin and fluoropyrimidine) significantly improved overall survival and progression-free survival in patients with HER2-positive metastatic gastric cancer compared to chemotherapy alone. Median overall survival was 13.8 months with chemotherapy plus trastuzumab versus 11.1 months with chemotherapy alone.
- The REAL-2 trial demonstrated that cisplatin plus capecitabine was as effective as cisplatin plus fluorouracil for advanced gastric cancer, with less toxicity. Cisplatin plus capecitabine has since
Invasive Lobular Carcinoma — Highlights from the First Ever ILC Symposium bkling
Steffi Osterreich, PhD, and Rachel Jankowitz, MD, of University of Pittsburgh Cancer Institute, join Heather Hillier, breast advocate and co-chair of the first international ILC Symposium, in offering an overview of Invasive Lobular Carcinoma and highlights from the conference, which took place in Pittsburgh in September 2016. The program was presented in collaboration with MBCN.
Lorlatinib shows efficacy in treating ALK-positive and ROS1-positive non-small cell lung cancer (NSCLC) in patients who have failed earlier treatments. In a study of 200 NSCLC patients treated with lorlatinib, the disease control rate was 86% for ALK-positive patients and 88% for ROS1-positive patients. Lorlatinib also achieved high response rates in central nervous system metastases of 41.7% for ALK-positive patients and 53.3% for ROS1-positive patients. Median progression-free survival was 11.8 months for ALK-positive patients and 7.6 months for ROS1-positive patients. Lorlatinib demonstrated clinical benefit in treating advanced AL
Osteoarthritis is a degenerative joint disease characterized by the breakdown of cartilage. It most commonly affects weight-bearing joints like the hips and knees. The cartilage, bone, synovial membrane, capsule, ligaments and muscles are all affected as the disease progresses. Symptoms include joint pain and stiffness that worsens with use of the affected joint. Treatment focuses on reducing pain and inflammation, maintaining joint mobility, and may include joint replacement surgery for severe cases.
This document summarizes treatment approaches for metastatic castration-resistant prostate cancer (mCRPC). It discusses definitions of CRPC and mechanisms of resistance. For mCRPC patients with PSADT >10 months and no symptoms, secondary hormonal therapies are recommended, while those with PSADT <10 months receive second-generation antiandrogens. Docetaxel remains first-line for symptomatic mCRPC, while abiraterone, enzalutamide, radium-223, and sipuleucel-T are also options. Detection of AR-V7 in circulating tumor cells may help determine if taxanes or AR-targeted therapies are most suitable. Ongoing treatment, monitoring of
Rheumatoid arthritis is a chronic autoimmune disease that causes inflammation and damage to joints. It affects around 1-3% of the global population. While its exact causes are unknown, genetic and environmental factors are believed to play a role. Key symptoms include tender, warm, swollen joints and morning stiffness lasting over an hour. Diagnosis is based on criteria such as the number and location of affected joints, presence of rheumatoid factor or anti-CCP antibodies, and response to treatment. Treatment aims to control symptoms, prevent further joint damage, and improve quality of life using medications such as methotrexate, sulfasalazine, biologics that target cytokines, and newer drugs like tofacitinib. The
Chair & Presenter, David R. Jones, MD, and Nathan A. Pennell, MD, PhD, FASCO, prepared useful Practice Aids pertaining to NSCLC for this CME/MOC activity titled “Adjuvant EGFR-Targeted Therapy as a Game Changer: How to Implement New Standards of Care in Multimodal Management of Stage I-III EGFR-Mutated NSCLC.” For the full presentation, downloadable Practice Aids, and complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/3mFfjji. CME/MOC credit will be available until December 2, 2022.
Each year, approximately 14 million people around the globe are diagnosed with cancer. About a third of cancer deaths can be prevented, which is why cancer awareness is so important. Different types of cancers are honored throughout the year so you can be aware of when each cancer awareness month is and which colored ribbon is used to represent it. We’ve compiled all current cancer awareness months and their appropriate ribbon colors into one easy-to-use chart. Cancer is a disease that can affect anyone at any time, and our infographic helps to spread awareness so that other people can be aware of the signs, symptoms, and risk factors for cancer. Awareness saves lives! View the full infographic at http://www.wheelsforwishes.org/cancer-awareness-ribbons/.
- The document summarizes key landmark clinical trials investigating treatments for metastatic gastric cancer.
- The ToGA trial found that adding trastuzumab (Herceptin) to standard chemotherapy (cisplatin and fluoropyrimidine) significantly improved overall survival and progression-free survival in patients with HER2-positive metastatic gastric cancer compared to chemotherapy alone. Median overall survival was 13.8 months with chemotherapy plus trastuzumab versus 11.1 months with chemotherapy alone.
- The REAL-2 trial demonstrated that cisplatin plus capecitabine was as effective as cisplatin plus fluorouracil for advanced gastric cancer, with less toxicity. Cisplatin plus capecitabine has since
Invasive Lobular Carcinoma — Highlights from the First Ever ILC Symposium bkling
Steffi Osterreich, PhD, and Rachel Jankowitz, MD, of University of Pittsburgh Cancer Institute, join Heather Hillier, breast advocate and co-chair of the first international ILC Symposium, in offering an overview of Invasive Lobular Carcinoma and highlights from the conference, which took place in Pittsburgh in September 2016. The program was presented in collaboration with MBCN.
- Oligometastatic disease refers to a limited number of metastases that may be amenable to local treatment.
- Stereotactic body radiation therapy (SBRT) for lung oligometastases from various primary cancers can achieve high rates of local control with minimal toxicity.
- Patient selection is important, with longer disease-free interval, fewer metastatic sites, and controlled primary tumor associated with improved outcomes after aggressive local therapy of oligometastases.
- Ongoing clinical trials are investigating SBRT for synchronous and metachronous oligometastatic disease to define optimal patient populations and treatment approaches.
Report Back from San Antonio Breast Cancer Symposium (SABCS 2022)bkling
Curious about the latest developments in Early-Stage Breast Cancer and Metastatic Breast Cancer Research? Join us as Dr. Anne Blaes, the Division Director of Hematology/Oncology/Transplantation and Professor in Hematology/Oncology at the University of Minnesota, breaks down the most recent developments released at the annual San Antonio Breast Cancer Symposium regarding early-stage and metastatic breast cancer research.
Metastatic bone disease: An old dogma and a new insightMohamed Abdulla
Metastatic bone disease is a challenging condition that places a heavy burden on patients. New insights into the cellular and molecular mechanisms have led to improved treatments. Cancer cells interact with the bone microenvironment through factors like RANKL, RANK, and osteoprotegerin, inducing a "vicious cycle" of bone destruction. Emerging therapies target these interactions by inhibiting RANKL with drugs like denosumab. Radiopharmaceuticals like radium-223 also show promise by targeting areas of new bone growth in metastases. While radiation remains important for pain relief, combination therapies offer the potential for improved outcomes in metastatic bone disease.
This document discusses the management of bone metastases. It begins by explaining how tumor cells interact with bone cells, disrupting normal bone metabolism and increasing osteoclast activity. This leads to skeletal complications over several years for cancers like myeloma, breast, and prostate. Common sites of bone metastases are then outlined. Treatment options discussed include systemic therapies like bisphosphonates and denosumab which target osteoclasts and RANKL, as well as local therapies like surgery, radiation, vertebroplasty, and kyphoplasty. Denosumab is positioned as an alternative to zoledronic acid, with potential advantages of subcutaneous dosing and reduced risks of osteonecrosis of the jaw and renal toxicity. Guidelines recommend
Osteoarthritis is a progressive degenerative joint disease characterized by the breakdown and eventual loss of articular cartilage in the joints. As cartilage breaks down, bones rub together causing pain, swelling, and loss of motion of the joints. The most common joints affected are weight-bearing joints like the hips, knees, and spine. Risk factors include age, obesity, joint injury, genetics, and repetitive joint stress from certain occupations and sports. The breakdown of cartilage is caused by an imbalance between the normal synthesis and degradation of cartilage components by chondrocytes within the cartilage. This leads to loss of cartilage cushioning between bones and development of bone spurs and cysts at the joint margins over time.
Fase III que utiliza Nab-Paclitaxel + Carboplatino y Pembrolizumab en NSCLC escamoso. El hazard ratio favorece a Nab paclitaxel en el análisis de subgrupos.
SHARE Presentation: New Developments in the Medical Treatment of Breast Cance...bkling
Dr. Cliff Hudis on the latest information on new breast cancer treatments. Dr. Hudis is Chief of Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center.
Recent advances in the diagnosis and treatment of thyroid cancerHealthXn
This document summarizes recent advances in the diagnosis and treatment of thyroid cancer by Professor Steven Boyages. It discusses the rising incidence of thyroid cancer in recent decades, which may be due to increased medical surveillance and technology. It describes a study that examined pathways to diagnosis for thyroid cancer patients in New South Wales, finding most were serendipitous discoveries. Factors like tumor size influenced diagnosis pathways. Minimally invasive thyroidectomy techniques and strategies for radioiodine ablation in low-risk thyroid cancer, including using recombinant human thyrotropin and lower radiation doses, are also summarized. Treatment of radioiodine-resistant thyroid cancer is an ongoing challenge.
The document discusses prostate cancer, including its anatomy, staging, Gleason scoring, and treatment options. It provides details on radiation therapy techniques like IMRT and Tomotherapy that tightly target the prostate gland while avoiding surrounding organs to minimize side effects. Brachytherapy seed implantation is also covered. Treatment protocols vary based on cancer risk but commonly involve a combination of radiation types and sometimes hormone therapy.
- Fibromyalgia affects 3 to 6 million Americans, with 80-90% being women who are usually diagnosed in middle age.
- It is characterized by widespread pain in the muscles and soft tissues. Common symptoms include fatigue, sleep issues, headaches, and tender points in various areas of the body.
- While drugs can help manage symptoms, natural therapies like exercise, stress reduction, and nutrition have shown more long-term promise for fibromyalgia sufferers. Regular exercise in particular can help reduce pain and fatigue and improve overall health.
Osteoarthritis is a type of joint disease that results from the breakdown of cartilage and underlying bone. It commonly affects the hands, feet, spine, and large weight-bearing joints like the hips and knees. The most common symptoms are joint pain, stiffness, and crackling noises. Risk factors include mechanical stress, excess weight, nerve impairment, and hereditary or hormonal conditions. It is diagnosed through x-rays, blood tests, and examination and shows features like bone spurs, cysts, and cartilage loss.
- RECIST provides standardized criteria for evaluating tumor response to treatment in clinical trials. It defines measurable lesions and how they are assessed, including complete response, partial response and disease progression based on tumor size changes.
- Key changes from WHO to RECIST included using the longest diameter of lesions rather than bidimensional measurements, limiting the number of target lesions assessed, and defining minimum lesion sizes.
- RECIST 1.1 further clarified disease progression definitions and included FDG-PET in detecting new lesions. Standardizing response criteria allows more consistent evaluation of cancer treatments across clinical trials.
Overview of Breast Health Problems with Focus on Benign Breast Conditions Reynaldo Joson
Breast - Benign and Malignant Conditions - Overview of Breast Health Problem - Benign Conditions of the Breast - ROJoson's Lecture to UP College of Medicine Level 4 Students - 13sept 16
This document discusses recent advances in the diagnosis and management of osteoporosis. It begins by defining osteoporosis and describing the changes in bone density that occur with age. It then discusses risk factors, medical conditions associated with increased risk, drugs that can reduce bone mass, and tools for assessing fracture risk such as FRAX. It provides guidelines on who should receive bone mineral density testing and describes new assessment tools. The document concludes by covering non-pharmacological and pharmacological prevention and treatment options for osteoporosis, including calcium, vitamin D, exercise, falls prevention, hormone therapy, bisphosphonates, and other medications.
Prostate cancer is the second most common cancer in men worldwide and the second most common cause of cancer death in men. It makes up around 10-15% of all male cancers. Hereditary factors like mutations in the BRCA1 and BRCA2 genes and a family history of prostate cancer can increase the risk. Screening tests for prostate cancer include a digital rectal exam and PSA blood test. Treatment depends on the stage and grade of cancer, and may include surgery, radiation therapy, hormone therapy, chemotherapy, and palliative care.
Este documento resume la osteoporosis, incluyendo su definición, epidemiología, manifestaciones clínicas, diagnóstico, tratamiento y prevención. La osteoporosis es una enfermedad esquelética caracterizada por la pérdida de masa ósea y deterioro de la microarquitectura ósea, lo que aumenta el riesgo de fracturas. Afecta a millones de personas en todo el mundo y causa fracturas óseas frecuentes. El diagnóstico se realiza mediante medición de densidad ósea y el tratamiento incluye
This deals with the current paradigm of treatment of osteosarcoma. It is an honest effort to clear the prevailing confusion in the treatment of osteosarcoma. I would be happy to get anyone
Bladder cancer is the fourth most common cancer in men and seventh most common in women. 90-95% of cases are transitional-cell carcinoma. Standard treatment for superficial bladder cancer is transurethral resection followed by adjuvant intravesical therapy to reduce relapse rates by 30-80%. For invasive bladder cancer, radical cystectomy provides 5-year survival rates ranging from 77% for stage I to 12% for stage IV disease. Combined modality therapy with chemotherapy and radiotherapy can yield 5-year survival rates of 50-69% and organ preservation rates of 38-45% for invasive bladder cancer.
1. Androgen deprivation therapy (ADT) for prostate cancer is associated with rapid bone loss and increased fracture risk. Several treatments have been shown to prevent bone loss and reduce fractures in men receiving ADT, including zoledronic acid, denosumab, and bisphosphonates.
2. Bone markers like N-telopeptide and bone-specific alkaline phosphatase can help predict risks of skeletal-related events and survival in men with bone metastases from prostate cancer. High bone marker levels are associated with worse outcomes.
3. Having multiple bone metastases is also associated with shorter time to first skeletal-related event and reduced survival compared to having fewer bone lesions. Normalizing elevated bone marker levels in response
The document discusses drug-induced osteoporosis, focusing on glucocorticoids, aromatase inhibitors, androgen deprivation therapy, Depo-provera, proton pump inhibitors, and selective serotonin reuptake inhibitors. It summarizes their effects on bone loss and fracture risk, mechanisms of action, and treatment approaches. Key findings include rapid bone loss associated with glucocorticoid use, increased fracture risk from aromatase inhibitors and androgen deprivation therapy for cancer patients, and conflicting data on fracture risk from proton pump inhibitor use.
- Oligometastatic disease refers to a limited number of metastases that may be amenable to local treatment.
- Stereotactic body radiation therapy (SBRT) for lung oligometastases from various primary cancers can achieve high rates of local control with minimal toxicity.
- Patient selection is important, with longer disease-free interval, fewer metastatic sites, and controlled primary tumor associated with improved outcomes after aggressive local therapy of oligometastases.
- Ongoing clinical trials are investigating SBRT for synchronous and metachronous oligometastatic disease to define optimal patient populations and treatment approaches.
Report Back from San Antonio Breast Cancer Symposium (SABCS 2022)bkling
Curious about the latest developments in Early-Stage Breast Cancer and Metastatic Breast Cancer Research? Join us as Dr. Anne Blaes, the Division Director of Hematology/Oncology/Transplantation and Professor in Hematology/Oncology at the University of Minnesota, breaks down the most recent developments released at the annual San Antonio Breast Cancer Symposium regarding early-stage and metastatic breast cancer research.
Metastatic bone disease: An old dogma and a new insightMohamed Abdulla
Metastatic bone disease is a challenging condition that places a heavy burden on patients. New insights into the cellular and molecular mechanisms have led to improved treatments. Cancer cells interact with the bone microenvironment through factors like RANKL, RANK, and osteoprotegerin, inducing a "vicious cycle" of bone destruction. Emerging therapies target these interactions by inhibiting RANKL with drugs like denosumab. Radiopharmaceuticals like radium-223 also show promise by targeting areas of new bone growth in metastases. While radiation remains important for pain relief, combination therapies offer the potential for improved outcomes in metastatic bone disease.
This document discusses the management of bone metastases. It begins by explaining how tumor cells interact with bone cells, disrupting normal bone metabolism and increasing osteoclast activity. This leads to skeletal complications over several years for cancers like myeloma, breast, and prostate. Common sites of bone metastases are then outlined. Treatment options discussed include systemic therapies like bisphosphonates and denosumab which target osteoclasts and RANKL, as well as local therapies like surgery, radiation, vertebroplasty, and kyphoplasty. Denosumab is positioned as an alternative to zoledronic acid, with potential advantages of subcutaneous dosing and reduced risks of osteonecrosis of the jaw and renal toxicity. Guidelines recommend
Osteoarthritis is a progressive degenerative joint disease characterized by the breakdown and eventual loss of articular cartilage in the joints. As cartilage breaks down, bones rub together causing pain, swelling, and loss of motion of the joints. The most common joints affected are weight-bearing joints like the hips, knees, and spine. Risk factors include age, obesity, joint injury, genetics, and repetitive joint stress from certain occupations and sports. The breakdown of cartilage is caused by an imbalance between the normal synthesis and degradation of cartilage components by chondrocytes within the cartilage. This leads to loss of cartilage cushioning between bones and development of bone spurs and cysts at the joint margins over time.
Fase III que utiliza Nab-Paclitaxel + Carboplatino y Pembrolizumab en NSCLC escamoso. El hazard ratio favorece a Nab paclitaxel en el análisis de subgrupos.
SHARE Presentation: New Developments in the Medical Treatment of Breast Cance...bkling
Dr. Cliff Hudis on the latest information on new breast cancer treatments. Dr. Hudis is Chief of Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center.
Recent advances in the diagnosis and treatment of thyroid cancerHealthXn
This document summarizes recent advances in the diagnosis and treatment of thyroid cancer by Professor Steven Boyages. It discusses the rising incidence of thyroid cancer in recent decades, which may be due to increased medical surveillance and technology. It describes a study that examined pathways to diagnosis for thyroid cancer patients in New South Wales, finding most were serendipitous discoveries. Factors like tumor size influenced diagnosis pathways. Minimally invasive thyroidectomy techniques and strategies for radioiodine ablation in low-risk thyroid cancer, including using recombinant human thyrotropin and lower radiation doses, are also summarized. Treatment of radioiodine-resistant thyroid cancer is an ongoing challenge.
The document discusses prostate cancer, including its anatomy, staging, Gleason scoring, and treatment options. It provides details on radiation therapy techniques like IMRT and Tomotherapy that tightly target the prostate gland while avoiding surrounding organs to minimize side effects. Brachytherapy seed implantation is also covered. Treatment protocols vary based on cancer risk but commonly involve a combination of radiation types and sometimes hormone therapy.
- Fibromyalgia affects 3 to 6 million Americans, with 80-90% being women who are usually diagnosed in middle age.
- It is characterized by widespread pain in the muscles and soft tissues. Common symptoms include fatigue, sleep issues, headaches, and tender points in various areas of the body.
- While drugs can help manage symptoms, natural therapies like exercise, stress reduction, and nutrition have shown more long-term promise for fibromyalgia sufferers. Regular exercise in particular can help reduce pain and fatigue and improve overall health.
Osteoarthritis is a type of joint disease that results from the breakdown of cartilage and underlying bone. It commonly affects the hands, feet, spine, and large weight-bearing joints like the hips and knees. The most common symptoms are joint pain, stiffness, and crackling noises. Risk factors include mechanical stress, excess weight, nerve impairment, and hereditary or hormonal conditions. It is diagnosed through x-rays, blood tests, and examination and shows features like bone spurs, cysts, and cartilage loss.
- RECIST provides standardized criteria for evaluating tumor response to treatment in clinical trials. It defines measurable lesions and how they are assessed, including complete response, partial response and disease progression based on tumor size changes.
- Key changes from WHO to RECIST included using the longest diameter of lesions rather than bidimensional measurements, limiting the number of target lesions assessed, and defining minimum lesion sizes.
- RECIST 1.1 further clarified disease progression definitions and included FDG-PET in detecting new lesions. Standardizing response criteria allows more consistent evaluation of cancer treatments across clinical trials.
Overview of Breast Health Problems with Focus on Benign Breast Conditions Reynaldo Joson
Breast - Benign and Malignant Conditions - Overview of Breast Health Problem - Benign Conditions of the Breast - ROJoson's Lecture to UP College of Medicine Level 4 Students - 13sept 16
This document discusses recent advances in the diagnosis and management of osteoporosis. It begins by defining osteoporosis and describing the changes in bone density that occur with age. It then discusses risk factors, medical conditions associated with increased risk, drugs that can reduce bone mass, and tools for assessing fracture risk such as FRAX. It provides guidelines on who should receive bone mineral density testing and describes new assessment tools. The document concludes by covering non-pharmacological and pharmacological prevention and treatment options for osteoporosis, including calcium, vitamin D, exercise, falls prevention, hormone therapy, bisphosphonates, and other medications.
Prostate cancer is the second most common cancer in men worldwide and the second most common cause of cancer death in men. It makes up around 10-15% of all male cancers. Hereditary factors like mutations in the BRCA1 and BRCA2 genes and a family history of prostate cancer can increase the risk. Screening tests for prostate cancer include a digital rectal exam and PSA blood test. Treatment depends on the stage and grade of cancer, and may include surgery, radiation therapy, hormone therapy, chemotherapy, and palliative care.
Este documento resume la osteoporosis, incluyendo su definición, epidemiología, manifestaciones clínicas, diagnóstico, tratamiento y prevención. La osteoporosis es una enfermedad esquelética caracterizada por la pérdida de masa ósea y deterioro de la microarquitectura ósea, lo que aumenta el riesgo de fracturas. Afecta a millones de personas en todo el mundo y causa fracturas óseas frecuentes. El diagnóstico se realiza mediante medición de densidad ósea y el tratamiento incluye
This deals with the current paradigm of treatment of osteosarcoma. It is an honest effort to clear the prevailing confusion in the treatment of osteosarcoma. I would be happy to get anyone
Bladder cancer is the fourth most common cancer in men and seventh most common in women. 90-95% of cases are transitional-cell carcinoma. Standard treatment for superficial bladder cancer is transurethral resection followed by adjuvant intravesical therapy to reduce relapse rates by 30-80%. For invasive bladder cancer, radical cystectomy provides 5-year survival rates ranging from 77% for stage I to 12% for stage IV disease. Combined modality therapy with chemotherapy and radiotherapy can yield 5-year survival rates of 50-69% and organ preservation rates of 38-45% for invasive bladder cancer.
1. Androgen deprivation therapy (ADT) for prostate cancer is associated with rapid bone loss and increased fracture risk. Several treatments have been shown to prevent bone loss and reduce fractures in men receiving ADT, including zoledronic acid, denosumab, and bisphosphonates.
2. Bone markers like N-telopeptide and bone-specific alkaline phosphatase can help predict risks of skeletal-related events and survival in men with bone metastases from prostate cancer. High bone marker levels are associated with worse outcomes.
3. Having multiple bone metastases is also associated with shorter time to first skeletal-related event and reduced survival compared to having fewer bone lesions. Normalizing elevated bone marker levels in response
The document discusses drug-induced osteoporosis, focusing on glucocorticoids, aromatase inhibitors, androgen deprivation therapy, Depo-provera, proton pump inhibitors, and selective serotonin reuptake inhibitors. It summarizes their effects on bone loss and fracture risk, mechanisms of action, and treatment approaches. Key findings include rapid bone loss associated with glucocorticoid use, increased fracture risk from aromatase inhibitors and androgen deprivation therapy for cancer patients, and conflicting data on fracture risk from proton pump inhibitor use.
This document discusses recommendations from the European Calcified Tissue Society (ECTS) regarding treatment after stopping denosumab therapy. It summarizes findings from ECTS papers in 2017 and 2021 on risks of rebound vertebral fractures when discontinuing denosumab. The ECTS recommends pretreatment or post-treatment with bisphosphonates to prevent bone mineral density loss and fractures after stopping denosumab, especially for those on long-term denosumab therapy of over 2.5 years. New Dutch guidelines advise treating with denosumab for 3 years, then reevaluating fracture risk before extending treatment another 3 years up to a maximum of 10 years, and ensuring adequate bisphosphonate treatment after stopping to prevent
Osteoarthritis is a common joint disease that worsens over time due to factors like aging, injury, and excess weight. It involves breakdown of cartilage in the joints. NSAIDs are commonly used for pain relief but can have side effects with long term use. Guidelines for managing osteoarthritis include lifestyle changes like exercise and weight loss, physical therapy, braces or other assistive devices, and medications like NSAIDs in the short term and occasionally corticosteroid injections. Surgery is considered as a last option for advanced cases.
El 17 de octubre de 2014, la Fundación Ramón Areces celebró una nueva conferencia del ciclo 'Envejecimiento, Sociedad y Salud: envejecimiento y enfermedad', que organiza en colaboración con el Centro de Estudios del Envejecimiento. En esta ocasión, el doctor Valentín Fuster, director del Centro Nacional de Investigaciones Cardiovasculares Carlos III- CNIC, habló sobre 'Enfermedad subclínica de corazón y cerebro: el reto de la década'. En esta entrevista previa a su intervención, deja claro que nunca es tarde para cuidarse y que la clave no está tanto en el corazón, sino en el cerebro, donde se toman las decisiones para llevar hábitos de vida saludables.
The document summarizes key information about prostate cancer including incidence, mortality rates, clinical stages, risk groups for localized prostate cancer, treatment options for advanced disease including hormone therapy and chemotherapy, and results from clinical trials of chemotherapy agents like docetaxel and cabazitaxel.
This document discusses several topics related to predicting toxicity after androgen deprivation therapy for prostate cancer, including:
1) Androgen deprivation therapy can cause rapid bone loss of 4-8% per year for the first few years after treatment.
2) Studies have shown patients receiving androgen deprivation therapy have higher rates of fractures compared to those not receiving the therapy.
3) Having more than 3 bone lesions is associated with shorter time to first skeletal-related event and decreased survival compared to having 3 or fewer bone lesions.
4) Bone marker levels, such as N-telopeptide, can help predict risk of skeletal-related events and survival outcomes in prostate cancer patients. Reductions in bone marker
Osteoporosis, How to diagnose and treat _ Oral and Infusion Treatment.pptxparyanti2
The VERT study found that daily treatment with risedronate significantly reduced the risk of new vertebral fractures by 41% and new morphometric vertebral fractures by 49% compared to placebo in postmenopausal women with osteoporosis over 3 years. Risedronate also reduced the risk of hip fractures by 39% and other nonvertebral fractures by 25%, although the results for nonvertebral fractures were not statistically significant. The study demonstrated that risedronate is a safe and effective treatment for reducing fracture risk in postmenopausal osteoporosis.
A great deal is happening in lupus-related research. This presentation will update participants on recent research developments and their impact on those affected by lupus. Dr. Petri will provide an overview of current lupus research and the prospects for the future of lupus treatments. Learn how to better manage your lupus and make knowledgeable decisions regarding your treatment plan.
The document discusses osteoporosis prevention and management. It describes how gynecologists can help achieve peak bone mass during adolescence and adulthood, prevent bone loss during peri-menopause through screening and treatment if needed, and manage age-related osteoporosis. Key roles include promoting physical activity and nutrition, addressing drug-related bone loss, and treating with exercise, calcium/vitamin D supplementation, and medications like bisphosphonates or hormones if screening shows low bone mineral density.
This document discusses glucocorticoid induced osteoporosis. It begins with an epidemiology section noting that glucocorticoids are the most common cause of secondary osteoporosis. Treatment options discussed include adequate calcium and vitamin D, exercise therapy, optimal treatment of underlying disease, smoking cessation, and drug therapies. Drug therapies shown to increase bone mineral density and reduce fractures include alendronate, risedronate, zoledronic acid, teriparatide, and denosumab. Head-to-head trials found that teriparatide was more effective at reducing fractures than alendronate. The EuroGIOPS study similarly found teriparatide more effective at improving bone mineral density and
The document summarizes key points from the 18th International Conference on Co-morbidities and Adverse Drug Reactions in HIV. It discusses findings related to bone health, cardiovascular health, and physical activity levels in people living with HIV. Regarding bone health, studies showed bone mineral density loss with tenofovir-containing antiretroviral therapy and PrEP. Loss was also seen with glucocorticoid use. For cardiovascular health, studies suggested lower risk of atherosclerotic events with NNRTI-based initial ART and possible lower risk with atazanavir. Physical activity levels were associated with comorbidity risk, with higher risk at lower activity levels.
Zoledronic acid administered once yearly through intravenous infusion was found to significantly reduce fractures more effectively than placebo. Over six years, yearly zoledronic acid preserved bone mass and continued fracture protection compared to discontinuing treatment after three years. It provided reductions in hip, vertebral, and non-vertebral fractures with no increase in safety risks like atrial fibrillation or renal impairment. A single infusion also reduced bone turnover markers more rapidly than weekly oral bisphosphonates.
Zoledronic acid administered once yearly through intravenous infusion was found to significantly reduce fractures more effectively than placebo. Over six years, yearly zoledronic acid preserved bone mass and continued fracture protection compared to discontinuing treatment after three years. It provided reductions in hip, vertebral, and non-vertebral fractures compared to placebo with no increase in safety risks over the long term. A single infusion of zoledronic acid also reduced bone turnover markers more rapidly than weekly oral alendronate.
This document discusses osteoporosis and its treatment. It defines osteoporosis as a bone mineral density (BMD) at least 2.5 standard deviations below the young adult mean. It lists common risk factors for osteoporotic fractures such as female sex, smoking, family history, and low calcium/vitamin D intake. It discusses screening tools like FRAX score and recommendations for BMD testing and lifestyle changes. It provides guidelines for initiating drug therapy and lists common osteoporosis treatments like bisphosphonates, denosumab, calcium/vitamin D, and raloxifene.
Professor Andrew Davies is an Intensivist working at Peninsula Health in Melbourne. He has performed clinical research in the field of critical care for 20 years, as a participating investigator in over 50 studies (mostly clinical trials), predominantly in the areas of critical care nutrition, mechanical ventilation and acute lung injury and severe sepsis. He is a past Vice Chair of the Australian and New Zealand Intensive Care Society Clinical Trials Group (ANZICS-CTG) with a special interest in nutrition in the ICU, and is a past Chair of the Australian and New Zealand Society of Parenteral and Enteral Nutrition (AuSPEN).
In this talk, Professor Davies tackles the often overlooked aspect of nutrition in the ICU and it’s potential benefits for our patients.
This document summarizes the state of the art in permanent prostate brachytherapy (PPB) based on literature and a large single-institution series. Key findings include:
1) PPB monotherapy provides excellent long-term cancer control for low-intermediate risk prostate cancer, with 10-year biochemical no evidence of disease rates of 88-96%.
2) For all risk groups, PPB monotherapy results in similar long-term outcomes as radical prostatectomy or external beam radiation in terms of cancer control and survival. However, PPB may have fewer side effects.
3) Salvage treatments after PPB fail provide limited cancer control due to high toxicity, but focal therapy aimed at the
Osteoporosis is a disease characterized by low bone mass and deterioration of bone tissue, leading to fragile bones that break easily. The document discusses several studies on the drug alendronate for treating and preventing osteoporosis. The studies found that alendronate increased bone mineral density, reduced the risk of fractures including vertebral and hip fractures, and was more effective at increasing bone density when combined with hormone replacement therapy compared to hormone replacement therapy alone.
Similar to Musculoskeletal Complications of Cancer and its Treatments (20)
Next-Generation Safety Assessment Tools for Advancing In Vivo to In Vitro Tra...InsideScientific
Join Prof. Victoria Hutter and Dr. Louis Scott as they showcase the application of high-content imaging and advanced cell lines for drug safety assessment.
Safety concerns play a significant role in the unsuccessful progression of candidate compounds in the later stages of drug development. Establishing the connection between in vitro endpoints and human health outcomes is essential.
In this webinar, Prof. Victoria Hutter and Dr. Louis Scott present a novel tool for in vitro safety assessment in drug development. The morph_ONE™ assay provides a human-centric approach to potentially fill specific regulatory gaps concerning safety issues. This tool is capable of profiling both human and rat alveolar macrophages, offering valuable insights for hazard identification and toxicity assessments. By bridging the divide between cellular effects and overall risk, it has the potential to enhance our understanding of safety-related aspects in drug development.
Key Topics Include:
- Explore distinct in vitro screening techniques for evaluating the safety of emerging inhaled products, facilitating early and informed decisions in compound selection and development.
- How high-content image analysis (HCIA) cell painting assays can be used as a forward-looking high-throughput screening tool, distinguishing unique response patterns in alveolar macrophages.
- Understand the use of the ImmuPHAGE™ and ImmuLUNG™ models in conducting customized evaluations focused on inhalation safety.
A Ready-to-Analyze High-Plex Spatial Signature Development Workflow for Cance...InsideScientific
In this webinar, Aditya Pratapa and Lorcan Sherry present a new workflow for analyzing multiplex immunoflurescence images.
Spatial Signatures are a new class of highly predictive biomarkers that measure the interactions and cellular densities of tumor and immune cells that compose the tumor microenvironment. Based on multiplex immunofluorescence, spatial signatures provide a deeper understanding of complex interactions between tumors and the immune system, enabling improved patient stratification for immunotherapies. A significant hurdle to date has been in developing a data analysis workflow that is straightforward and user-friendly to transform the data rich images into meaningful quantitative spatial signatures.
In this webinar, Aditya and Lorcan review the key features of the new PhenoImager HT 2.0 data analysis workflow. This workflow introduces a simplified framework from scanning to analyzing spectrally unmixed multiplex immunofluorescence images generated on the PhenoImager HT platform. The ready-to-analyze data can be directly imported into image analysis software such as Visiopharm. This presentation covers key aspects of data analysis elements such as image QC, segmentation, phenotyping, and verification – all essential for creating outputs that support the development of a spatial signature.
Key Topics Include:
- Understand Akoya’s new HT 2.0 data analysis workflow
- The challenges in multiplex immunofluorescence analysis and the use of AI and cell
lineage segmentation considerations
- Explore OracleBio’s image analysis workflow incorporating Visiopharm
- Evaluation of analysis data to facilitate spatial profiling and interpretation
Molecule Transport across Cell Membranes: Electrochemical Quantification at t...InsideScientific
In this webinar, Dr. Sabine Kuss will discuss the importance of transmembrane molecule exchange and how to detect and quantify membrane transport of molecules in cells.
Complex biological processes, such as the transport of molecules across cell membranes, are difficult to understand using purely biological methodologies. Investigating cellular transport processes is challenging, because of the highly complex chemical composition of cells and the diffusion of molecules in and around cells at low concentrations. The development and advancement of electroanalytical methods over the last two decades has enabled the monitoring of living cells and their interaction with the environment, including external stimuli, such as pharma-molecules.
This presentation emphasizes electrochemical and electrophysiological methods of detection and quantification but also makes a comparison to other bioanalytical approaches. Join us to discover a substantial diversity in methods used to monitor the transport of cell metabolites, crucial for cell survival, and pharmaceutical compounds, involved in cell characteristics such as drug resistance.
Key Topics Include:
- Understanding transmembrane molecule transport through bioanalytical methods
- Electrochemical approaches to monitor molecule transport across cell membranes
- What bioanalytical and especially electrochemical approaches can reveal
- Challenges associated with instrument limitations
Exploring Predictive Biomarkers and ERK1/2 Phosphorylation: A New Horizon in ...InsideScientific
In this webinar, Dr. Victor Arrieta highlights the link between p-ERK activation and improved survival in rGBM patients using anti-PD-1 immunotherapy.
Recurrent glioblastoma (rGBM) has displayed a varied response to anti-PD-1 immunotherapy, necessitating the identification of predictive biomarkers. Through extensive analyses and 3 clinical studies, we have identified that activation of the MAPK/ERK signaling pathway, particularly ERK1/2 phosphorylation (p-ERK), is associated with longer overall survival (OS) in rGBM patients receiving PD-1 blockade. Initially, enrichment of BRAF/PTPN11 mutations was reported in 30% of responsive rGBM patients, prompting the investigation of p-ERK as a potential marker beyond these mutations.
Our research has unraveled an association between p-ERK abundance and better clinical outcomes following PD-1 blockade, with p-ERK mainly localized in tumor cells. Notably, high p-ERK GBMs contained unique microglia and macrophage phenotypes with elevated MHC class II expression, suggesting a novel interplay between MAPK activation and the tumor immune microenvironment.
While these insights establish a pivotal role for p-ERK in predicting PD-1 blockade response in rGBM, the implementation in clinical settings calls for further validation and accuracy. Nonetheless, these findings pave the way for more personalized and effective immunotherapy strategies, emphasizing the significance of the tumor microenvironment and its interaction with therapeutic interventions in GBM.
Key Topics Include:
- The activation of the MAPK signaling pathway, specifically ERK1/2 phosphorylation (p-ERK), is identified as a predictive biomarker for longer overall survival in recurrent glioblastoma (eGBM) patients undergoing PD-1 blockade
- High p-ERK tumors in rGBM present a distinct myeloid cell phenotype with elevated MHC class II expression, signifying a connection between MAPK pathway activation and the immune microenvironment
- The implementation of p-ERK as a predictive biomarker in clinical settings requires further validation and exploration of variables impacting its evaluation
Exploring Estrogen’s Role in Metabolism and the Use of 13C-Labeled Nutrients ...InsideScientific
Dr. Reilly Enos and Dr. Eran Levin discuss estrogen's metabolic impact and how isotopic labeling and 13C-labeled nutrients can be used for animal physiology and nutrition research.
Reilly Enos, PhD – Harnessing the power of estrogen to regulate metabolic processes
Dr. Reilly Enos’ research focuses on the role that sex steroids and their receptors play in regulating metabolic processes, particularly in the setting of obesity. In this webinar, Dr. Enos will discuss his research on tissue-specific fluctuations of sex steroids throughout the estrous cycle in mice, provide insights into the importance of the quantity of estrogen necessary to impact physiological processes, as well as an understanding of the central versus peripheral effects of estrogen action.
Eran Levin, PhD – Unlocking Insights: Utilizing 13C Labeled Nutrients for Cutting-Edge Physiology and Nutrition Research
Dr. Eran Levin will discuss the potential of using 13C-labeled nutrients in physiology and nutrition research in animal models. Specifically, he will share practical tips for designing and conducting experiments using isotopic labeling techniques and demonstrate how they can provide unprecedented insights into metabolic pathways, nutrient utilization, and behaviors in both vertebrate and invertebrate models including insects, reptiles, and mammals.
Key Topics Include:
- The role that estrogen plays in regulating metabolic and behavioral processes in males and females
- The tissue-specific fluctuations of sex steroids throughout the estrous cycle
- Insight into the importance of tissue-specificity in developing hormonal therapies
- The importance of estrogen quantity in regulating physiological processes
- Understand the diverse range of 13C labeled nutrients available
- Specific applications of labeled amino acids in studies of protein metabolism, cellular signaling, and typical nutrient utilization
- How to integrate 13C labeling techniques with respirometry for a comprehensive assessment of metabolic processes, energy expenditure, and substrate utilization in animal models
- How to calculate metabolic rates in free-flying animals using 13C bicarbonate
Longitudinal Plasma Samples: Paving the Way for Precision OncologyInsideScientific
Experts present a cell-free plasma biobank and describe the role of longitudinal plasma samples for cancer research, disease monitoring, and biomarker development.
Through liquid biopsies, it is now possible to repeatedly and non-invasively interrogate the molecular landscape of solid tumors via a blood draw over the whole treatment course. Until now, liquid biopsies can be used for screening, disease monitoring and prognosis. Circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) have been the most explored targets in this technology for commercial applications up to the present time.
In collaboration with a continuously expanding oncology network, Indivumed Services has established a unique high-quality cell-free plasma biobank that is exclusively focused on collecting longitudinal whole blood samples from cancer patients. This allows molecular insight by providing quick access to longitudinal plasma from cancer patients that have undergone treatment. ctDNA can then be isolated from longitudinal cell-free plasma to allow for monitoring of disease progression by providing diagnostic and prognostic information, potentially in real time.
Key Topics Include:
- Gain insights into Indivumed Services’ longitudinal plasma collection process
- Understand the advantages and benefits of utilizing longitudinal plasma samples for cancer research
- Explore applications of longitudinal plasma samples for biomarker research and development of companion diagnostics
Fully Characterized, Standardized Human Induced Pluripotent Stem Cell Line an...InsideScientific
This document summarizes a webinar presented by Andrew Gaffney and Erin Knock of STEMCELL Technologies. They discussed STEMCELL's development of the healthy control human iPSC line SCTi003-A and single-use iPSCdirect product, which were manufactured to high quality standards. They also discussed STEMCELL's neural progenitor cells derived from SCTi003-A, which can be expanded over multiple passages while maintaining their ability to differentiate into neurons and astrocytes. The neural progenitor cells demonstrate expected marker expression and can be cryopreserved and re-thawed while retaining their differentiation potential.
How to Create CRISPR-Edited T Cells More Efficiently for Tomorrow's Cell Ther...InsideScientific
Ian Foster and Steven Loo-Yong-Kee discuss Artisan Bio's STAR-CRISPR system for optimized gene editing in cell therapy, with a focus on the genetifc modification of T cells for cancer immunotherapy.
Cell therapy is an emerging field with great promise for the treatment of various diseases. One of the most exciting areas of cell therapy is the use of T cells that have been genetically modified to recognize and kill cancer cells. While the use of T cells for cancer immunotherapy has tremendous promise, there is still room for improvement. The efficiency, expansion, and functionality of T cells can be enhanced by genetic modification using the STAR-CRISPR system.
Artisan Bio is a biotechnology company focused on developing a CRISPR-mediated editing platform to improve the efficacy and safety of cell therapy products. In this webinar, we will provide a comprehensive overview of Artisan Bio’s STAR-CRISPR system, which is designed to improve the specificity and efficiency of gene editing for cell therapies. We will explain the system’s key components and how we are using a risk-based approach to optimize and validate the editing platform. The webinar will focus on Artisan Bio’s approach to building T cell OS/APPS through iterative improvements to achieve best-in-class editing capabilities and improved cell health metrics.
Key Topics Include:
- Learn about Artisan Bio’s proprietary high-performance STAR-CRISPR system for improving the specificity and efficiency of gene editing for cell therapies
- Explore Artisan Bio’s risk-based, systems approach to technology development, including how to implement Design of Experiments (DoE) and Quality by Design (QbD) principles to optimize and validate any process
- Case study of the application of QbD to Artisan Bio’s STAR-CRISPR platform to edit T cells for cancer immunotherapy with preliminary data showing improved efficacy, expansion, and functionality
Peripheral and Cerebral Vascular Responses Following High-Intensity Interval ...InsideScientific
Dr. Bert Bond and Max Weston will present an overview on their study investigating the effects high-intensity interval exercise has on cerebrovascular health.
Physical activity reduces the risk of developing cardiovascular diseases (CVD) and dementia. This benefit cannot be explained by changes in traditional CVD risk factors alone, and direct improvements in vascular health are thought to play a key role. However, our understanding of how exercise can be optimized for improvements in blood-vessel health is limited.
High-intensity interval exercise (HIIE) is known to improve peripheral vascular function, and there is a growing interest in the effects of HIIE on cerebrovascular health. However, it is not clear whether the acute improvements in peripheral vascular function following HIIE are also seen in the major blood-vessels of the brain.
In the Bond lab’s study, 30 minutes of HIIE completed at both 75% and 90% V̇O2max improved peripheral vascular function 1 and 3h following exercise in healthy young adults, compared with work-matched continuous moderate-intensity exercise and a sedentary control condition. By contrast, cerebrovascular function was unchanged following all conditions. This is the first study to identify that acute improvements in peripheral vascular function following high-intensity interval exercise are not mirrored by improvements in cerebrovascular function in healthy young adults.
Leveraging Programmable CRISPR-Associated Transposases for Next-Generation Ge...InsideScientific
Dr. Sam Sternberg discusses a novel CRISPR-Cas9 system using programmable, RNA-guided transposase, and highlights its implications for kilobase-scale genome engineering in cell and gene therapies.
The utility of programmable, RNA-guided CRISPR-Cas systems in genome engineering continues to evolve. Nature has afforded scientists novel and diverse gene editing functionality, from nuclease-dependent CRISPR-Cas9 to second-generation base and prime editors that do not produce double-strand breaks.
In this webinar, Dr. Sam Sternberg describes a new CRISPR-Cas9 paradigm relying on nuclease-deficient bacterial transposons that catalyze RNA-guided integration of mobile genetic elements into the genome. The discovery of a fully programmable, RNA-guided transposase lays the foundation for kilobase-scale genome engineering with broad applications for developing cell and gene therapies.
Key Topics Include:
- The basics of first- and second-generation CRISPR-Cas technologies from a scientist at the forefront of their development
- Mechanisms, accommodation, and cell type diversity of CRISPR-Cas programmable transposition
- How transposase factor coordination enables highly specific, genome-wide DNA integration to target sites
- Implications of programmable transposases that obviate the need for DNA double-strand breaks and homologous recombination
Simple Tips to Significantly Improve Rodent Surgical OutcomesInsideScientific
Dr. Marcel Perret-Gentil presents six simple-to-implement techniques to significantly improve surgical outcomes.
You may feel proficient, even confident in performing rodent surgery; however, you may be surprised how simple improvements can have a huge impact to your animal’s recovery and data. The presentation is designed for individuals who have minimal or no rodent surgical skills but is also a great opportunity for those with considerable experience wanting to improve outcomes as well as teach such key principles.
Key Topics Include:
- Improve surgical outcomes that will lessen post-op morbidity and mortality
- Improve data yield after rodent surgery
- Implementation of key principles into a rodent surgical program
Cardiovascular Autonomic Dysfunction in the Post-COVID Landscape: Detection a...InsideScientific
This document discusses cardiovascular autonomic dysfunction in post-COVID patients. It begins with a case study of a 41-year-old woman who developed post-COVID symptoms like fatigue, palpitations and orthostatic intolerance. Tests showed she had postural orthostatic tachycardia syndrome (POTS). Between 10-15% of COVID patients develop long COVID, and 30% of highly symptomatic long COVID patients have POTS. Tilt testing, active standing tests and Holter monitoring can help diagnose POTS and other forms of autonomic dysfunction. Treatment focuses on lifestyle changes, compression garments, increasing fluids and salts, and regulating heart rate and blood pressure with medications. Further research is still
Creating Better Gene-Edited Cell Lines with the FAST-HDR SystemInsideScientific
Cell lines are the core of biological research. Scientists need cell lines for drug development, basic biology research, safety testing, and biologic therapeutic production. Since the 1980s, genetic manipulation has allowed researchers to tailor cell lines to the experiment or production purpose. Over time, the requirements for these cell lies have risen. In many cases, the cells require multiple genetic edits and must produce data that passes FDA. Moreover, the current funding environment often requires rapid delivery of these cells so scientists can produce data to support further budget and/or investment. This is particularly acute for knock-in cell lines. Current technologies may take months to complete a cell line, allow a limited number of edits, and often have off-target effects that are not suitable for FDA filings. ExpressCells uses its patented FAST-HDR plasmid--along with CRISPR, to address these problems. The FAST-HDR process can precisely knock-in multiple genes (while supporting other types of genetic modifications), ensure precise placement of these edits, and deliver them months faster than competing technologies.
This webinar will discuss the basis of the FAST-HDR technology and illustrate several uses. The first part is a presentation by Oscar Perez-Leal, MD, the inventor of the technology. Oscar will discuss the problems he faced as a researcher and how FAST-HDR was designed to address them. He will outline the details of the technology, the history of its development, and several examples where he used FAST-HDR. The second part is a conversation with Jon Weidanz, PhD. Jon will outline the challenges he faced at AbeXXa and how he selected a FAST-HDR custom cell line for his project. He'll outline the learnings from using this cell line, some of which were unexpected, but valuable to future development.
By attending this program, attendees will:
- Understand the current challenges in creating custom gene-edited cell lines
- Know the technology underlying the FAST-HDR gene-editing system, including its use with CRISPR
- Be able to describe the advantages of the FAST-HDR system
- Learn about several case studies using gene-edited cell lines
Functional Recovery of the Musculoskeletal System Following Injury - Leveragi...InsideScientific
Watch Dr. Sarah Greising discuss the current pathophysiologic understanding of the skeletal muscle remaining following traumatic musculoskeletal injuries.
Volumetric muscle loss (VML) injuries result in the abrupt loss of skeletal muscle fibers, causing chronic functional disability in part due to limited muscle regeneration and vast co-morbidities. With a focus on clinically relevant outcome measurements for skeletal muscle function in both small and large animal models of VML injury, this webinar presents various near-term interventions for the restoration of tissue function following complex injuries. Interventions evaluated focus on regenerative rehabilitation approaches using regenerative pharmaceuticals to correct underlying muscle pathophysiology.
Designing Causal Inference Studies Using Real-World DataInsideScientific
In this webinar, experts provide an overview of causal inference, along with step-by-step guidance to designing these studies using real-world healthcare data.
Causal inference is used to answer cause and effect research questions and yield estimates of effect. Causal study design considerations and statistical methods address the effects of confounding variables and other potential biases and allow researchers to answer questions such as, “Does treatment A produce better patient outcomes compared to Treatment B?”
Causal study interpretations have traditionally been restricted to randomized controlled trials; however, causal inference applied to observational healthcare data is growing in importance, driven by the need for generalizable and rapidly delivered real-world evidence to inform regulatory, payer, and patient/provider decision making. The application of causal inference methods leads to stronger and more powerful evidence. When these techniques are applied to observational data, the results generated are both from and for the real world.
Presenters walk through several real-world case studies including the PCORI-funded BESTMED study and a collaborative study with a prominent pharmacy payer.
Social Media Data: Opportunities and Insights for Clinical ResearchInsideScientific
Many new data are emerging in recent years - real time data is collected through digital health technologies, including apps and wearables, monitoring data, social media data, public datasets, and patient organization data, in addition to primary and secondary datasets.
Real life data are highly informative and can be used to address a range of challenges throughout the product life cycle. Data from social media can generate valuable insights as patients often gather in digital communities to get answers and share their experiences. Conversations on social networks merit special consideration as they can have real world influence over treatment management decisions.
Social media data can reveal the motivations that impact patient healthcare decisions and behaviors through each stage of the care pathway. These data provide both the patient and caregiver perspectives at the same time. For this reason, conversations on social networks offer an opportunity to deepen our understanding on:
- The fears and hopes associated with patient treatments
- Daily needs and difficulties patients are facing in managing their disease
- The impact of disease on patient health related quality of life
- Identification in real life of the stages of the care pathway and patient perceptions
- Reactions to health policies
Watch this webinar for insights on how to collect, use, analyze, and interpret social media data in different contexts. Our experts share knowledge from over fifteen years of successfully developing and adapting algorithms to treat this kind of data.
We Are More Than What We Eat Dietary Interventions Depend on Sex and Genetic ...InsideScientific
To learn more visit: https://insidescientific.com/webinar/we-are-more-than-what-we-eat-dietary-interventions-depend-on-sex-and-genetic-background/
Despite evidence that sex and genetic background are key factors in the response to diet, most studies of how diet regulates metabolic health and even longevity in mice examine only a single strain and sex.
Using multiple strains and both male and female mice, Dr Lamming's team has found that improvements in metabolic health and in longevity in response to reduced levels of protein or specific amino acids strongly depend on sex and strain. While some phenotypes were conserved across strains and sexes, including increased glucose tolerance and energy expenditure, they observed high variability in adiposity, insulin sensitivity, and circulating hormones. Using a multi-omics approach, they identified mega-clusters of differentially expressed hepatic genes, metabolites, and lipids associated with each phenotype, gaining new insight into role of the energy balance hormone FG21 in the response to protein restriction.
Antibody Discovery by Single B Cell Screening on Beacon®InsideScientific
Amy Sheng, PhD provides an overview of antibody screening platforms and presents applications and case studies using the Beacon® platform for antibody discovery.
Single B cell screening is a powerful and efficient strategy for generating antigen-specific monoclonal antibodies. Distinguished with fluorescence-activated B cell sorting, the Beacon® platform is based on plasma cell screening, making it easier to obtain antibody genes.
The Beacon® single-cell optofluidic system combines a unique optoelectro positioning (OEP) technology with novel microfluidic technology. It can be used to accurately select single cells on a chip, perform multiple single-cell assays, and export target cells based on specific results. The Beacon® optofluidic platform preserves the diversity of B cells, generating high-quality positive hits at an early stage of discovery and avoiding the loss of “good clones”.
Key Topics Include:
- B cell differentiation and development
- Pros and cons of mainstream antibody screening platforms
- Mechanisms, applications, and case studies using the Beacon® platform for antibody screening
- Sino Biological’s capacity using the Beacon® platform
Experimental Design Considerations to Optimize Chronic Cardiovascular Telemet...InsideScientific
Phil Griffiths, PhD, presents a summary of chronic cardiovascular telemetry studies and considerations for experimental design.
Ensuring you collect the best and most physiologically accurate data from your chronic telemetry experiments requires careful planning and experimental design. This webinar will give an insight into the practical aspects of designing chronic animal experiments to set you on the best path for success. The benefits of chronic studies, how to select the most appropriate sample size for your study, some basic tips and tricks for data acquisition and handling, and how to ensure high animal welfare are discussed.
Key Topics Include:
- What are the benefits of chronic over acute studies?
- How to decide the best sample sizes and the length of experiments?
- Basic tips for data acquisition and handling
- How to maintain high animal welfare standards
Strategic Approaches to Age-Related Metabolic Insufficiency and Transition in...InsideScientific
In this webinar, Dr. Dennis Turner delves into dementia syndrome, the metabolic changes that occur, and the importance of proper physiological monitoring of animal models.
Brain metabolism transforms with normal aging, and transient, dynamic metabolic insufficiency may underlie critical progression from aging into dementia syndrome and Alzheimer’s disease (AD). Age-related brain metabolism balances vascular-related substrate supply and transport mechanisms into extracellular space to neurons with cellular metabolic needs and utilization. Dynamic metabolic insufficiency can occur when there is intermittent supply-demand mismatch.
Adequacy of neurovascular coupling to provide sufficient cerebral blood flow (CBF) to meet neuronal demand in vivo in a mouse AD model, compared to aged controls were studied. Dr. Turner’s lab analyzed the response to maximal neuronal metabolic demands, spreading depression and anoxia, using imaging, CBF measurements, and oxygen and glucose levels. These in vivo studies require human-similar anesthesia conditions, through monitoring temperature, blood pressure/pulse oximetry, and respiration, to maintain homeostasis. The lab confirmed abnormal neurovascular coupling in a mouse model of AD in response to these metabolic challenges, showing disruption much earlier in dementia than in equivalently aged individuals. Chronic metabolic treatments could influence dementia syndrome progression.
Remote Sensing and Computational, Evolutionary, Supercomputing, and Intellige...University of Maribor
Slides from talk:
Aleš Zamuda: Remote Sensing and Computational, Evolutionary, Supercomputing, and Intelligent Systems.
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Inter-Society Networking Panel GRSS/MTT-S/CIS Panel Session: Promoting Connection and Cooperation
https://www.etran.rs/2024/en/home-english/
Immersive Learning That Works: Research Grounding and Paths ForwardLeonel Morgado
We will metaverse into the essence of immersive learning, into its three dimensions and conceptual models. This approach encompasses elements from teaching methodologies to social involvement, through organizational concerns and technologies. Challenging the perception of learning as knowledge transfer, we introduce a 'Uses, Practices & Strategies' model operationalized by the 'Immersive Learning Brain' and ‘Immersion Cube’ frameworks. This approach offers a comprehensive guide through the intricacies of immersive educational experiences and spotlighting research frontiers, along the immersion dimensions of system, narrative, and agency. Our discourse extends to stakeholders beyond the academic sphere, addressing the interests of technologists, instructional designers, and policymakers. We span various contexts, from formal education to organizational transformation to the new horizon of an AI-pervasive society. This keynote aims to unite the iLRN community in a collaborative journey towards a future where immersive learning research and practice coalesce, paving the way for innovative educational research and practice landscapes.
The use of Nauplii and metanauplii artemia in aquaculture (brine shrimp).pptxMAGOTI ERNEST
Although Artemia has been known to man for centuries, its use as a food for the culture of larval organisms apparently began only in the 1930s, when several investigators found that it made an excellent food for newly hatched fish larvae (Litvinenko et al., 2023). As aquaculture developed in the 1960s and ‘70s, the use of Artemia also became more widespread, due both to its convenience and to its nutritional value for larval organisms (Arenas-Pardo et al., 2024). The fact that Artemia dormant cysts can be stored for long periods in cans, and then used as an off-the-shelf food requiring only 24 h of incubation makes them the most convenient, least labor-intensive, live food available for aquaculture (Sorgeloos & Roubach, 2021). The nutritional value of Artemia, especially for marine organisms, is not constant, but varies both geographically and temporally. During the last decade, however, both the causes of Artemia nutritional variability and methods to improve poorquality Artemia have been identified (Loufi et al., 2024).
Brine shrimp (Artemia spp.) are used in marine aquaculture worldwide. Annually, more than 2,000 metric tons of dry cysts are used for cultivation of fish, crustacean, and shellfish larva. Brine shrimp are important to aquaculture because newly hatched brine shrimp nauplii (larvae) provide a food source for many fish fry (Mozanzadeh et al., 2021). Culture and harvesting of brine shrimp eggs represents another aspect of the aquaculture industry. Nauplii and metanauplii of Artemia, commonly known as brine shrimp, play a crucial role in aquaculture due to their nutritional value and suitability as live feed for many aquatic species, particularly in larval stages (Sorgeloos & Roubach, 2021).
ESPP presentation to EU Waste Water Network, 4th June 2024 “EU policies driving nutrient removal and recycling
and the revised UWWTD (Urban Waste Water Treatment Directive)”
EWOCS-I: The catalog of X-ray sources in Westerlund 1 from the Extended Weste...Sérgio Sacani
Context. With a mass exceeding several 104 M⊙ and a rich and dense population of massive stars, supermassive young star clusters
represent the most massive star-forming environment that is dominated by the feedback from massive stars and gravitational interactions
among stars.
Aims. In this paper we present the Extended Westerlund 1 and 2 Open Clusters Survey (EWOCS) project, which aims to investigate
the influence of the starburst environment on the formation of stars and planets, and on the evolution of both low and high mass stars.
The primary targets of this project are Westerlund 1 and 2, the closest supermassive star clusters to the Sun.
Methods. The project is based primarily on recent observations conducted with the Chandra and JWST observatories. Specifically,
the Chandra survey of Westerlund 1 consists of 36 new ACIS-I observations, nearly co-pointed, for a total exposure time of 1 Msec.
Additionally, we included 8 archival Chandra/ACIS-S observations. This paper presents the resulting catalog of X-ray sources within
and around Westerlund 1. Sources were detected by combining various existing methods, and photon extraction and source validation
were carried out using the ACIS-Extract software.
Results. The EWOCS X-ray catalog comprises 5963 validated sources out of the 9420 initially provided to ACIS-Extract, reaching a
photon flux threshold of approximately 2 × 10−8 photons cm−2
s
−1
. The X-ray sources exhibit a highly concentrated spatial distribution,
with 1075 sources located within the central 1 arcmin. We have successfully detected X-ray emissions from 126 out of the 166 known
massive stars of the cluster, and we have collected over 71 000 photons from the magnetar CXO J164710.20-455217.
The debris of the ‘last major merger’ is dynamically youngSérgio Sacani
The Milky Way’s (MW) inner stellar halo contains an [Fe/H]-rich component with highly eccentric orbits, often referred to as the
‘last major merger.’ Hypotheses for the origin of this component include Gaia-Sausage/Enceladus (GSE), where the progenitor
collided with the MW proto-disc 8–11 Gyr ago, and the Virgo Radial Merger (VRM), where the progenitor collided with the
MW disc within the last 3 Gyr. These two scenarios make different predictions about observable structure in local phase space,
because the morphology of debris depends on how long it has had to phase mix. The recently identified phase-space folds in Gaia
DR3 have positive caustic velocities, making them fundamentally different than the phase-mixed chevrons found in simulations
at late times. Roughly 20 per cent of the stars in the prograde local stellar halo are associated with the observed caustics. Based
on a simple phase-mixing model, the observed number of caustics are consistent with a merger that occurred 1–2 Gyr ago.
We also compare the observed phase-space distribution to FIRE-2 Latte simulations of GSE-like mergers, using a quantitative
measurement of phase mixing (2D causticality). The observed local phase-space distribution best matches the simulated data
1–2 Gyr after collision, and certainly not later than 3 Gyr. This is further evidence that the progenitor of the ‘last major merger’
did not collide with the MW proto-disc at early times, as is thought for the GSE, but instead collided with the MW disc within
the last few Gyr, consistent with the body of work surrounding the VRM.
Describing and Interpreting an Immersive Learning Case with the Immersion Cub...Leonel Morgado
Current descriptions of immersive learning cases are often difficult or impossible to compare. This is due to a myriad of different options on what details to include, which aspects are relevant, and on the descriptive approaches employed. Also, these aspects often combine very specific details with more general guidelines or indicate intents and rationales without clarifying their implementation. In this paper we provide a method to describe immersive learning cases that is structured to enable comparisons, yet flexible enough to allow researchers and practitioners to decide which aspects to include. This method leverages a taxonomy that classifies educational aspects at three levels (uses, practices, and strategies) and then utilizes two frameworks, the Immersive Learning Brain and the Immersion Cube, to enable a structured description and interpretation of immersive learning cases. The method is then demonstrated on a published immersive learning case on training for wind turbine maintenance using virtual reality. Applying the method results in a structured artifact, the Immersive Learning Case Sheet, that tags the case with its proximal uses, practices, and strategies, and refines the free text case description to ensure that matching details are included. This contribution is thus a case description method in support of future comparative research of immersive learning cases. We then discuss how the resulting description and interpretation can be leveraged to change immersion learning cases, by enriching them (considering low-effort changes or additions) or innovating (exploring more challenging avenues of transformation). The method holds significant promise to support better-grounded research in immersive learning.
The ability to recreate computational results with minimal effort and actionable metrics provides a solid foundation for scientific research and software development. When people can replicate an analysis at the touch of a button using open-source software, open data, and methods to assess and compare proposals, it significantly eases verification of results, engagement with a diverse range of contributors, and progress. However, we have yet to fully achieve this; there are still many sociotechnical frictions.
Inspired by David Donoho's vision, this talk aims to revisit the three crucial pillars of frictionless reproducibility (data sharing, code sharing, and competitive challenges) with the perspective of deep software variability.
Our observation is that multiple layers — hardware, operating systems, third-party libraries, software versions, input data, compile-time options, and parameters — are subject to variability that exacerbates frictions but is also essential for achieving robust, generalizable results and fostering innovation. I will first review the literature, providing evidence of how the complex variability interactions across these layers affect qualitative and quantitative software properties, thereby complicating the reproduction and replication of scientific studies in various fields.
I will then present some software engineering and AI techniques that can support the strategic exploration of variability spaces. These include the use of abstractions and models (e.g., feature models), sampling strategies (e.g., uniform, random), cost-effective measurements (e.g., incremental build of software configurations), and dimensionality reduction methods (e.g., transfer learning, feature selection, software debloating).
I will finally argue that deep variability is both the problem and solution of frictionless reproducibility, calling the software science community to develop new methods and tools to manage variability and foster reproducibility in software systems.
Exposé invité Journées Nationales du GDR GPL 2024
Deep Software Variability and Frictionless Reproducibility
Musculoskeletal Complications of Cancer and its Treatments
1. Click to edit Master title style
Click to edit Master subtitle style
2021-11-18 1
Andrea Bonetto, PhD
Musculoskeletal Complications of Cancer
and its Treatments
Associate Professor
Surgery
Indiana University
2. Click to edit Master title style
Click to edit Master subtitle style
2021-11-18 2
Musculoskeletal Complications of Cancer
and its Treatments
An expert presents new research on
cancer and cachexia, and their
complications to anti-cancer treatment.
4. •Frequent in malignancy
•Reduced response to treatments
•Weight loss correlated with mortality
•Accounts for ~1/3 of cancer deaths
•Will cause the deaths of ~150,000
Americans every year
Cancer cachexia
There is currently no cure for cachexia
5. Preservation of muscle mass prolongs survival in tumor hosts
(Benny Klimek et al., 2010; Zhou et al., 2010)
Cancer patients with cachexia show severe chemotherapy toxicity
Patients with higher muscle mass are more resistant to chemotherapy
(Prado et al., 2011, 2013; Antoun et al., 2010)
Pro-anabolic strategies counteract chemotherapy effects on muscle
(Le Bricon et al., 1995; Damrauer et al., 2008; Garcia et al., 2008; Fanzani et al., 2011; Chen et al., 2015)
The role of skeletal muscle mass in cancer
6. • 1.8 million cases of cancer in the US, 600,000 will die
• Over 19 million cancer survivors by 2024
• Weakness and fatigue affect 70-100% of patients receiving cancer
treatments
• Persistent muscle weakness following chemotherapy
Poorer QOL, worse outcomes, relevant costs
(American Cancer Society, 2021; Siegel et al., 2021)
Chemotherapy toxicities in cancer: impact on skeletal muscle
10. Cancer affects muscle function, both in males and in females
Bonetto Lab, unpublished
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11. Bonetto Lab, unpublished
Colorectal cancer contributes to reduced activity in mice
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**
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Vehicle
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***
*
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Frequency (Hz)
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(g)
EDL - Force
*** *** *** *** ***
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*** *** *** *** ***
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100µm
CHEMOTHERAPY
Chemotherapy drives loss of muscle mass and function
Barreto et al., Oncotarget 2016
Barreto, Mandili et al., Front Physiol 2016
13. Bonetto Lab, unpublished
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F a tig u e
C o n tra c tio n #
%
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* * * * *
* * * *
Cisplatin affects muscle function in vivo
14. Bonetto Lab, unpublished
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15. Barreto et al., Oncotarget 2016
Barreto, Mandili et al., Front Physiol 2016
Cancer and chemotherapy activate different signaling pathways
22. Bone and muscle: a long-lasting relationship
Bonetto and Bonewald, Basic and Applied Bone Biology 2019
23. Unbalances in bone- and muscle-derived biochemical factors
may play a role in the pathogenesis of cachexia
Myokines
IL-6
IGF-1
Myostatin
FGF-2
BAIBA
Irisin
…
Osteokines
Activin A
TGF-β
IGF-1
BMP-2
RANKL
…
Bone
Muscle
Bone and muscle: a long-lasting relationship
24. Vehicle Cisplatin
Essex, Pin et al., Front Endocrinol 2019
V
C
0
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20
30
BV/TV
%
***
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Barreto et al., Sci Rep 2017
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25. Essex, Pin et al., Front Endocrinol 2019
Generation of marrow-
flushed bone CM (48h)
Myotubes exposed to bone
CM (48h)
Tibiae excised
>48h after last
treatment
Bone-derived soluble factors may participate in muscle wasting
27. Bisphosphonates prevent muscle weakness in a murine model of
breast-cancer induced bone metastases
Waning et al., 2015 Nat Med
Pamidronate improves muscle mass and function in burn children
Borsheim et al., 2015 JBMR; Pin et al., 2019 Front Endocrinol
Bisphosphonates are bone-targeting anti-resorptive agents
Bisphosphonates promote osteoclast apoptosis and inhibit osteoclastic bone resorption
Hughes et al. 1995 J Bone Miner Res; Mundy and Yoneda 1998 N Engl J Med
28. Essex, Pin et al., Front Endocrinol 2019
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Bisphosphonates preserve trabecular bone in combination with cisplatin
29. Essex, Pin et al., Front Endocrinol 2019
Zoledronate improves muscle mass and strength in cisplatin-treated animals
V
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30. Bonetto et al., Front Physiol 2016
Waning et al., Nat Med 2015
Non-bone metastatic cancers promote loss of muscle with differential effects on bone
31. BMI (kg/m2) 30.5 ± 3.7 33.7 ± 5.2 27.6 ± 4.9b
SMI (cm2/m2) 45.6 ± 6.0 49.8 ± 8.2 39.6 ± 5.1aa bbb
Visceral Fat (cm2) 156.5 ± 59.5 132.7 ± 64.1 90.3 ± 59.5aa
Pin et al., under review
Fearon et al., Lancet Oncol, 2011
Diagnostic Criteria:
1. Weight loss >5% (prior 6 months)
2. Weight loss >2% + BMI <20kg/m2
3. Weight loss >2% + Sarcopenia
Control
OvCa
(no cachexia)
OvCa
(cachexia)
Skeletal muscle
Intramuscular fat
Visceral adipose
Subcutaneous adipose
Ovarian cancer presents with evidence of muscle wasting
32. ES-2 OVARIAN CANCER
Pin et al., JCSM 2018
5
Control
ES-2
C
ontrol
ES-2
-4
-2
0
2
4
Grams
(g)
BW change
***
BW
Muscle
C
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t
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l
E
S
-
2
0.00
0.05
0.10
0.15
0.20
Weight
/
100mg
IBW
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***
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100mg
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***
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***
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Ovarian cancer is accompanied by loss of muscle and bone
ES-2 tumors recapitulate the
clinical presentation of HGS-OC
33. Pin et al., under review
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***
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2
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ume
(ml)
0.4
0.6
0.8
1.0
Quad
/
100mg
IBW
***
##
$$
0.4
0.6
GSN
/
100mg
IBW
***
###
$
0.10
0.15
0.20
TA
/
100mg
IBW
***
###
Bone
Preservation of bone is also beneficial for muscle mass
34. Osteocytes
CTX-I
CTX-I CTX-I
CTX-I
Pin et al., under review
C
2
C
1
2
C
2
6
E
S
-
2
0
10
20
30
RANKL (CM)
pg/ml
* $$
C
o
n
t
r
o
l
E
S
-
2
0
200
400
600
RANKL (plasma)
pg/ml
**
C
2
6
I
D
8
O
V
C
A
R
3
0
5
10
15
50
100
150
Fold
change
RANKL mRNA expression
***
**
Bone homeostasis: the role of RANKL
ZA
E
S-2
ES-
2
+
Z
A
Tb.N
**
$$$
##
C ZA
ES-2
ES-2
+
ZA
0
10
20
30
Tb.Pf
1/µm
*
##
$$$
C ZA
ES-2
ES-2
+
ZA
0
100
200
300
Conn.Dn
1/µm
3
$$
C
Z
A
E
S
-2
E
S
-2
+
ZA
0
2
4
6
8
Tnfsf11/Tnfrsf11b
Fold
change
ratio
***
###
$
C Z
A
E
S
-
2
E
S
-2
+
ZA
0
100
200
300
RANKL
pg/ml
**
$
##
35. Normal ovary Clear cell carcinoma Serous
adenocarcinoma
Serous papillary
adenocarcinoma
Transitional cell
carcinoma
RANKL
Methyl
green
Pin et al., under review
Low RANKL expression
(n=281)
High RANKL expression
(n=92)
C
o
n
t
r
o
l
O
v
C
a
0.0
0.5
1.0
1.5
2.0
2.5
CTX-1
ng/ml
**
C
o
n
t
r
o
l
O
v
C
a
0.0
0.2
0.4
0.6
0.8
RANKL
mol/l
*
0.0 0.5 1.0 1.5 2.0 2.5
0.0
0.2
0.4
0.6
0.8
Correlation
CTX-1
sRANKL
R=0.40**
Ovarian cancer associates with RANKL-dependent bone turnover
36. Activation of RANK signaling in myofibers drives muscle atrophy
and weakness in denervated mice
Dufresne et al., Am J Physiol Cell Physiol 2016
Blockade of RANKL by OPG-Fc improves the muscle phenotype in dystrophic animals
Dufresne et al., Acta Neuropathol Commun 2018
RANKL mediates muscle atrophy and dysfunction in a mouse model of COPD
Xiong et al., Am J Respir Cell Mol Biol 2021
RANKL inhibition improves muscle strength and insulin sensitivity (in mice) and restores bone
mass (in osteoporotic women)
Bonnet et al., JCI 2019
Role of RANKL in skeletal muscle
37. Pin et al., under review
P
B
S
R
A
N
K
L
0
5
1 0
1 5
2 0
H S M M m y o tu b e s iz e
F
ib
e
r
d
ia
m
e
te
r
(
m
m
)
***
P
B
S
R
A
N
K
L
0
5
1 0
1 5
2 0
C 2 C 1 2 m y o tu b e s iz e
F
ib
e
r
d
ia
m
e
te
r
(
m
m
)
**
MyHC
C2C12
PBS
RANKL
HSMM
PBS
RANKL
MyHC
PBS RANKL
207
75
RANKL promotes muscle atrophy
38. Pin et al., under review
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
0
5 0 0
1 0 0 0
1 5 0 0
2 0 0 0
2 5 0 0
R A N K L
p
g
/m
l
***
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
0
2 0 0
4 0 0
6 0 0
8 0 0
O P G
p
g
/m
l
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
0
5 0
1 0 0
1 5 0
2 0 0
R A N K L /O P G ra tio
F
o
ld
c
h
a
n
g
e
***
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
0 .1 0
0 .1 5
0 .2 0
0 .2 5
0 .3 0
T A
W
e
i
g
h
t
/
1
0
0
m
g
I
B
W
* *
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
0 .4 5
0 .5 0
0 .5 5
0 .6 0
0 .6 5
0 .7 0
0 .7 5
G S N
W
e
i
g
h
t
/
1
0
0
m
g
I
B
W
*
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
1 0 0 0
1 5 0 0
2 0 0 0
2 5 0 0
3 0 0 0
C S A
µm
2
*
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
6
8
1 0
1 2
1 4
F o rc e
m
N
×m
*
l
i
n
e
w
e
e
k
w
e
e
k
w
e
e
k
e
e
k
0 .0 4 0
0 .0 4 5
0 .0 5 0
0 .0 5 5
0 .0 6 0
B M D
g
/
c
m
2
* * *
e
l
i
n
e
w
e
e
k
w
e
e
k
w
e
e
k
e
e
k
0 .2 5
0 .3 0
0 .3 5
0 .4 0
0 .4 5
0 .5 0
B M C
g
A A V -N U L L
A A V -R A N K L
*
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
0
5 0 0
1 0 0 0
1 5 0 0
2 0 0 0
2 5 0 0
R A N K L
p
g
/m
l
***
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
0
2 0 0
4 0 0
6 0 0
8 0 0
O P G
p
g
/m
l
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
0
5 0
1 0 0
1 5 0
2 0 0
R A N K L /O P G ra tio
F
o
ld
c
h
a
n
g
e
***
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
0 .1 0
0 .1 5
0 .2 0
0 .2 5
0 .3 0
T A
W
e
i
g
h
t
/
1
0
0
m
g
I
B
W
**
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
0 .4 5
0 .5 0
0 .5 5
0 .6 0
0 .6 5
0 .7 0
0 .7 5
G S N
W
e
i
g
h
t
/
1
0
0
m
g
I
B
W
*
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
1 0 0 0
1 5 0 0
2 0 0 0
2 5 0 0
3 0 0 0
C S A
µm
2
*
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
6
8
1 0
1 2
1 4
F o rc e
m
N
×m
*
e
l
i
n
e
w
e
e
k
w
e
e
k
w
e
e
k
e
e
k
0 .0 4 0
0 .0 4 5
0 .0 5 0
0 .0 5 5
0 .0 6 0
B M D
g
/
c
m
2
** *
e
l
i
n
e
w
e
e
k
w
e
e
k
w
e
e
k
w
e
e
k
0 .2 5
0 .3 0
0 .3 5
0 .4 0
0 .4 5
0 .5 0
B M C
g
A A V -N U L L
A A V -R A N K L
*
AAV-NULL AAV-RANKL
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
0
5 0 0
1 0 0 0
1 5 0 0
p
g
/
m
l
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
0
2 0 0
4 0 0
6 0 0
p
g
/
m
l
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
0
5 0
1 0 0
1 5 0
F
o
ld
c
h
a
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
0 .1 0
0 .1 5
0 .2 0
0 .2 5
W
e
ig
h
t
/
1
0
0
* *
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
0 .4 5
0 .5 0
0 .5 5
0 .6 0
0 .6 5
W
e
ig
h
t
/
1
0
0
*
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
1 0 0 0
1 5 0 0
2 0 0 0
2 5 0 0
3 0 0 0
C S A
µm
2
*
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
6
8
1 0
1 2
1 4
F o rc e
m
N
×m
*
B
a
s
e
l
i
n
e
1
w
e
e
k
2
w
e
e
k
3
w
e
e
k
4
w
e
e
k
0 .0 4 0
0 .0 4 5
0 .0 5 0
0 .0 5 5
0 .0 6 0
B M D
g
/
c
m
2
* * *
B
a
s
e
l
i
n
e
1
w
e
e
k
2
w
e
e
k
3
w
e
e
k
4
w
e
e
k
0 .2 5
0 .3 0
0 .3 5
0 .4 0
0 .4 5
0 .5 0
B M C
g
A A V -N U L L
A A V -R A N K L
*
A
A
V
-
N
U
L
L
A
V
-
R
A
N
K
L
0
5
1 0
1 5
2 0
2 5
B V /T V
%
* *
A
A
V
-
N
U
L
L
A
V
-
R
A
N
K
L
0 .0 0
0 .0 2
0 .0 4
0 .0 6
0 .0 8
T b .T h
µm
** *
A
A
V
-
N
U
L
L
A
V
-
R
A
N
K
L
0 .0
0 .1
0 .2
0 .3
0 .4
0 .5
T b .S p
µm
**
A
A
V
-
N
U
L
L
A
V
-
R
A
N
K
L
0
1
2
3
4
T b .N
1
/µm
* **
A
A
V
-
N
U
L
L
A
V
-
R
A
N
K
L
0
5
1 0
1 5
2 0
2 5
T b .P f
1
/µm
A
A
V
-
N
U
L
L
A
V
-
R
A
N
K
L
0
1 0 0
2 0 0
3 0 0
4 0 0
5 0 0
C o n n .D n
1
/µm
AAV-NULL AAV-RANKL
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
0
5 0 0
1 0 0 0
1 5 0 0
2 0 0 0
2 5 0 0
R A N K L
p
g
/m
l
***
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
0
2 0 0
4 0 0
6 0 0
8 0 0
O P G
p
g
/m
l
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
0
5 0
1 0 0
1 5 0
2 0 0
R A N K L /O P G ra tio
F
o
ld
c
h
a
n
g
e
***
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
0 .1 0
0 .1 5
0 .2 0
0 .2 5
0 .3 0
T A
W
e
ig
h
t
/
1
0
0
m
g
I
B
W
**
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
0 .4 5
0 .5 0
0 .5 5
0 .6 0
0 .6 5
0 .7 0
0 .7 5
G S N
W
e
ig
h
t
/
1
0
0
m
g
I
B
W
*
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
1 0 0 0
1 5 0 0
2 0 0 0
2 5 0 0
3 0 0 0
C S A
µm
2
*
A
A
V
-
N
U
L
L
A
A
V
-
R
A
N
K
L
6
8
1 0
1 2
1 4
F o rc e
m
N
×m
*
B M D B M C
High RANKL is sufficient to cause muscle and bone loss
39. GAPDH (37 kDa)
RANKL (32 kDa)
1- Marker
2- rmRANKL
3- C26
4- C26pR
1 2 3 4
C
2
6
C
2
6
p
R
0
50
100
150
200
RANKL
rg/ml
**
C
2
6
C
2
6
p
R
0
5
10
15
20
25
FBW
Grams
(g)
*
C
2
6
C
2
6
p
R
0
5
10
15
20
25
FBW - Tumor
Grams
(g)
*
C
2
6
C
2
6
p
R
0
5
10
15
Carcass
Grams
(g)
*
C
2
6
C
2
6
p
R
0.0
0.2
0.4
0.6
0.8
Quadriceps
Weight
/
100mg
IBW
*
C
2
6
C
2
6
p
R
0.0
0.2
0.4
0.6
Heart
Weight
/
100mg
IBW
C
2
6
C
2
6
p
R
0
2
4
6
Liver
Weight
/
100mg
IBW
C
2
6
C
2
6
p
R
0.0
0.2
0.4
0.6
0.8
1.0
Spleen
Weight
/
100mg
IBW
C
2
6
C
2
6
p
R
0.0
0.5
1.0
1.5
WAT
Weight
/
100mg
IBW
C
2
6
C
2
6
p
R
0
500
1000
1500
RANKL
rg/ml
**
C
2
6
C
2
6
p
R
0
200
400
600
800
OPG
rg/ml
C
2
6
C
2
6
p
R
0.00
0.05
0.10
0.15
0.20
0.25
TA
Weight
/
100mg
IBW
C
2
6
C
2
6
p
R
0.0
0.2
0.4
0.6
GSN
Weight
/
100mg
IBW
**
C
2
6
C
2
6
p
R
0
50
100
150
200
RANKL
rg/ml
**
C
2
6
C
2
6
p
R
0
5
10
15
20
25
FBW
Grams
(g)
*
C
2
6
C
2
6
p
R
0
5
10
15
20
25
FBW - Tumor
Grams
(g) *
C
2
6
C
2
6
p
R
0
5
10
15
Carcass
Grams
(g)
*
C
2
6
C
2
6
p
R
0.0
0.2
0.4
0.6
0.8
Quadriceps
Weight
/
100mg
IBW
*
C
2
6
C
2
6
p
R
0.0
0.2
0.4
0.6
Heart
Weight
/
100mg
IBW
C
2
6
C
2
6
p
R
0
2
4
6
Liver
Weight
/
100mg
IBW
C
2
6
C
2
6
p
R
0.0
0.2
0.4
0.6
0.8
1.0
Spleen
Weight
/
100mg
IBW
C
2
6
C
2
6
p
R
0.0
0.5
1.0
1.5
WAT
Weight
/
100mg
IBW
C
2
6
C
2
6
p
R
0
500
1000
1500
RANKL
rg/ml
**
C
2
6
C
2
6
p
R
0
200
400
600
800
OPG
rg/ml
C
2
6
C
2
6
p
R
0
2
4
6
8
RANKL/OPG
Fold
change
**
C
2
6
C
2
6
p
R
0.00
0.05
0.10
0.15
0.20
0.25
TA
Weight
/
100mg
IBW
C
2
6
C
2
6
p
R
0.0
0.2
0.4
0.6
GSN
Weight
/
100mg
IBW
**
I
B
W
d
a
y
7
d
a
y
9
d
a
y
1
0
d
a
y
1
1
80
85
90
95
100
105
Body weight change
%IBW
C26
C26pR
*
*
L
e
a
n
m
.
F
a
t
m
.
0
5
10
15
20
25
EchoMRI
Grams
(g)
C26
C26pR
*
C
2
6
C
2
6
p
R
0.0
0.2
0.4
0.6
0.8
Tumor
Grams
(g)
C
2
6
C
2
6
p
R
0.00
0.02
0.04
0.06
BMD
g/cm
2
***
C
2
6
C
2
6
p
R
0.0
0.1
0.2
0.3
0.4
BMC
Grams
(g)
*
C
2
6
C
2
6
p
R
0
10
20
30
BV/TV
Grams
(g)
*
C
2
6
C
2
6
p
R
0.00
0.02
0.04
0.06
0.08
0.10
Tb.Th
µm
C
2
6
C
2
6
p
R
0.00
0.05
0.10
0.15
0.20
0.25
Tb.Sp
µm
*
Tb.N Tb.Pf Conn.Dn
C
2
6
C
2
6
p
R
0
50
100
150
200
RANKL
rg/ml
**
C
2
6
C
2
6
p
R
0
5
10
15
20
25
FBW
*
C
2
6
C
2
6
p
R
0
5
10
15
20
25
FBW - Tumor
Grams
(g)
*
C
2
6
C
2
6
p
R
0
5
10
15
Carcass
Grams
(g)
*
C
2
6
C
26
p
R
0.0
0.2
0.4
0.6
0.8
Quadriceps
Weight
/
100mg
IBW
*
C
2
6
C
2
6
p
R
0.0
0.2
0.4
0.6
Heart
C
2
6
C
2
6
p
R
0
2
4
6
Liver
Weight
/
100mg
IBW
C
2
6
C
2
6
p
R
0.0
0.2
0.4
0.6
0.8
1.0
Spleen
Weight
/
100mg
IBW
C
2
6
C
2
6
p
R
0.0
0.5
1.0
1.5
WAT
Weight
/
100mg
IBW
C
2
6
C
2
6
p
R
0
500
1000
1500
RANKL
rg/ml
**
C
2
6
C
2
6
p
R
0
200
400
600
800
OPG
rg/ml
C
2
6
C
2
6
p
R
0
2
4
6
8
RANKL/OPG
Fold
change
**
C
2
6
C
2
6
p
R
0.00
0.05
0.10
0.15
0.20
0.25
TA
Weight
/
100mg
IBW
C
2
6
C
2
6
p
R
0.0
0.2
0.4
0.6
GSN
Weight
/
100mg
IBW
**
I
B
W
d
a
y
7
d
a
y
9
d
a
y
1
0
d
a
y
1
1
80
85
90
95
100
105
Body weight change
%IBW
C26
C26pR
*
*
L
e
a
n
m
.
F
a
t
m
.
0
5
10
15
20
25
EchoMRI
Grams
(g)
C26
C26pR
*
C
2
6
C
2
6
p
R
0.0
0.2
0.4
0.6
0.8
Tumor
Grams
(g)
C
2
6
C
2
6
p
R
0.00
0.02
0.04
0.06
BMD
g/cm
2
***
C
2
6
C
2
6
p
R
0.0
0.1
0.2
0.3
0.4
BMC
Grams
(g)
*
C
2
6
C
2
6
p
R
0
10
20
30
BV/TV
Grams
(g)
*
C
2
6
C
2
6
p
R
0.00
0.02
0.04
0.06
0.08
0.10
Tb.Th
µm
C
2
6
C
2
6
p
R
0.00
0.05
0.10
0.15
0.20
0.25
Tb.Sp
µm
*
C
26
C
26pR
0
500
1000
1500
RANKL
rg/ml
**
C
26
C
26pR
0
200
400
600
800
OPG
rg/ml
C
26
C
26pR
0
2
4
6
8
RANKL/OPG
Fold
change
**
C
26
C
26pR
0.00
0.05
0.10
0.15
0.20
0.25
TA
Weight
/
100mg
IBW
C
26
C
26pR
0.0
0.2
0.4
0.6
GSN
Weight
/
100mg
IBW
**
80
85
90
95
100
105
%IBW
Lean
m
.
Fat m
.
0
5
10
15
20
25
EchoMRI
Grams
(g)
C26
C26pR
*
0.0
0.2
0.4
0.6
0.8
Grams
(g)
C
26
C
26pR
0.00
0.02
0.04
0.06
BMD
g/cm
2
***
C
26
C
26pR
0.0
0.1
0.2
0.3
0.4
BMC
Grams
(g)
*
C
26
C
26pR
0
10
20
30
BV/TV
Grams
(g)
*
C
26
C
26pR
0.00
0.02
0.04
0.06
0.08
0.10
Tb.Th
µm
C
26
C
26pR
0
1
2
3
4
Tb.N
1/µm
*
C
26
C
26pR
0
50
100
150
200
250
Tb.Pf
1/µm
C26 C26pR
RANKL worsens cancer-induced muscle and bone loss
Pin et al., under review
40. IgG2a R Ab ES-2 + IgG2a ES-2 + R Ab
Pin et al., under review
E
S
-
2
E
S
-
2
+
R
A
b
0
5
1 0
M y o tu b e s iz e
F
ib
e
r
d
ia
m
e
te
r
(
m
m
)
**
MyHC
ES-2
ES-2+R Ab
Anti-RANKL treatments preserve muscle and bone mass in cancer
41. Cancer and chemotherapy promote the development of cachexia,
accompanied by loss of muscle and bone mass
The muscle/bone crosstalk is affected by cancer and chemotherapy
Anti-resorptive strategies protect from muscle and bone loss
in cancer or following chemotherapy
Growth of non-metastatic cancers can result in bone loss
RANKL is a new regulator of muscle size in cachexia
Conclusions
42. Acknowledgments
Dept. Anatomy, Cell Biology & Physiology -
ICMH
Lynda Bonewald
Lilian Plotkin
Dept. Otolaryngology – Head & Neck Surgery
Thomas O’Connell
Dept. Surgery
Teresa Zimmers
Ashok Narasimhan
Rafael Barreto
abonetto@iu.edu
@A_Bonetto_PhD
43. Click to edit Master title style
Click to edit Master subtitle style
2021-11-18 43
Andrea Bonetto, PhD
Associate Professor
Surgery
Indiana University
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This file is intended to assist you in creating your master Virtual Poster Presentation. There are a number of slide layouts to choose from, and we ask that you stay true to these options for uniformity across the program. That said, there are several options to choose from and you may pick and choose from them as you wish.
TITLE SLIDE – You will notice that there is a space for your institution logo. Please delete the grey box, and replace it with the logo. There is also a large, high resolution sample image in the back with the rest of the slide hovering overtop with a transparency applied. If you have an image that you feel is suitable to this space, please feel free to change it out (and ensure that you right click the image and “send it to the back”). When inserting your headshot, please right click the place holder image, click ’Change picture’, and select a square image that it at least 300px x 300px.