This document describes a study that used various regression models to identify genes whose DNA methylation rates are strongly correlated with breast cancer survival rates. The researchers used datasets containing survival data, genomic data, and methylation data for over 1,000 breast cancer patients. They applied proportional hazards regression, elastic net regression, ridge regression, and lasso regression to identify genes where high methylation rates are favorably or adversely correlated with survival. The goal is to better understand how methylation relates to survival and aid in developing personalized therapy strategies.
Determining the intrinsic quality of a summary (for Automatic Summarization E...Nishita Jaykumar
The document discusses factors that contribute to the quality of summaries generated by an automatic summarization system. It examines how the topic being summarized, source documents, and summarization method all impact the results. The system is evaluated by comparing summary content to curated medical resources to determine how well the high-level information is conveyed in a condensed format.
This study assessed the safety, tolerability, and immunogenicity of a polyvalent WT1 peptide vaccine in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). Sixteen patients received at least one vaccination of four WT1 peptides designed to stimulate both CD4 and CD8 T-cell responses. Vaccinations were well-tolerated with no discontinuations due to toxicity. Two AML patients experienced relapse-free survival over 1 year, exceeding the duration of their first remission, suggesting potential clinical benefit from the vaccine. The vaccine engaged protective immune responses against WT1, warranting further clinical trials.
ResQu: A Framework for Automatic Evaluation of Knowledge-Driven Automatic Sum...Nishita Jaykumar
Automatic generation of summaries that capture the salient aspects of a search resultset
(i.e., automatic summarization) has become an important task in biomedical research. Automatic
summarization offers an avenue for overcoming the information overload problem
prevalent in large online digital libraries. However, across many of the knowledge-driven
approaches for automatic summarization it is not always clear which features highly impact
or influence the quality of a summary. Instead, there has been considerable focus on
utilizing schema knowledge to facilitate browsing and exploration of generated summaries
a posteriori. Informative features should not be ignored, since they could be utilized to
help optimize the models that generate these semantic summaries in the first place.
In this research, we adopt a leave-one-out approach to assess the impact of various
features on the quality of automatically generated summaries that contain structured background
knowledge. We first create the gold standard summaries, using information-theoretic
methods, by extraction and validation, then the semantic summaries are transformed into
an equivalent textual format. Finally, various similarity metrics, such as cosine similarity,
euclidean distance, and Jensen-Shannon divergence are computed under different feature
combinations, to assess summary quality against the textual gold standard. We report on
the relative importance of the various features used to automatically generate the semantic
summaries in a biomedical application. Our evaluation suggests that the proposed approach
is an effective automatic
Continuous Exposure to Chrysotile Asbestos Can CauseGhazal Khan
This document summarizes a study that found continuous exposure to chrysotile asbestos can induce transformation of human mesothelial cells through signaling of HMGB1 and TNF-α, similar to effects of crocidolite asbestos exposure. Both asbestos types induced epithelial-to-mesenchymal transition in cells, characterized by downregulation of E-cadherin and phosphorylation/nuclear translocation of β-catenin. While crocidolite exposure induced sustained gene expression changes and HMGB1 release, chrysotile effects returned to baseline within 5-8 weeks. Continuous chrysotile exposure was required to maintain elevated HMGB1 levels, supporting the role of fiber persistence in biological activity.
Opening remarks on IO in 1st-Line NSCLCMauricio Lema
This document discusses immune-oncology and its role as a new paradigm for first-line treatment of non-small cell lung cancer (NSCLC). It provides a brief history of developments in immunotherapy including checkpoint inhibitors like pembrolizumab. Clinical trials results are presented showing that combining pembrolizumab with chemotherapy improves overall survival across all PD-L1 expression levels for both non-squamous and squamous NSCLC. The document concludes that immune checkpoint blockade is transforming NSCLC treatment.
The document describes a study that identified distinct methylation subtypes of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) using genome-wide DNA methylation data. Four subtypes were identified with high (HM), intermediate (IM), low (LM), or minimal (MM) levels of methylation. The subtypes showed differences in epigenetically silenced genes and frequencies of genetic alterations. Specifically, the HM subtype was enriched for ERBB2 alterations and ARID1A mutations. The findings suggest etiological and biological differences between the subtypes that could help direct clinical care.
Zauderer, M.G., et al. Clinical Cancer Research, 2017.sellasq4
1. This randomized phase II trial evaluated the WT1 peptide vaccine galinpepimut-S combined with GM-CSF and Montanide in patients with malignant pleural mesothelioma after multimodality therapy.
2. The trial randomized 41 patients to galinpepimut-S plus adjuvants or adjuvants alone. The control arm was stopped early due to a futility analysis showing progression within 1 year in over 10 of the first 20 patients.
3. Trends toward improved progression-free survival (10.1 vs 7.4 months) and overall survival (22.8 vs 18.3 months) were observed in the vaccine arm compared to control, but the trial was
This document describes a study that used various regression models to identify genes whose DNA methylation rates are strongly correlated with breast cancer survival rates. The researchers used datasets containing survival data, genomic data, and methylation data for over 1,000 breast cancer patients. They applied proportional hazards regression, elastic net regression, ridge regression, and lasso regression to identify genes where high methylation rates are favorably or adversely correlated with survival. The goal is to better understand how methylation relates to survival and aid in developing personalized therapy strategies.
Determining the intrinsic quality of a summary (for Automatic Summarization E...Nishita Jaykumar
The document discusses factors that contribute to the quality of summaries generated by an automatic summarization system. It examines how the topic being summarized, source documents, and summarization method all impact the results. The system is evaluated by comparing summary content to curated medical resources to determine how well the high-level information is conveyed in a condensed format.
This study assessed the safety, tolerability, and immunogenicity of a polyvalent WT1 peptide vaccine in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). Sixteen patients received at least one vaccination of four WT1 peptides designed to stimulate both CD4 and CD8 T-cell responses. Vaccinations were well-tolerated with no discontinuations due to toxicity. Two AML patients experienced relapse-free survival over 1 year, exceeding the duration of their first remission, suggesting potential clinical benefit from the vaccine. The vaccine engaged protective immune responses against WT1, warranting further clinical trials.
ResQu: A Framework for Automatic Evaluation of Knowledge-Driven Automatic Sum...Nishita Jaykumar
Automatic generation of summaries that capture the salient aspects of a search resultset
(i.e., automatic summarization) has become an important task in biomedical research. Automatic
summarization offers an avenue for overcoming the information overload problem
prevalent in large online digital libraries. However, across many of the knowledge-driven
approaches for automatic summarization it is not always clear which features highly impact
or influence the quality of a summary. Instead, there has been considerable focus on
utilizing schema knowledge to facilitate browsing and exploration of generated summaries
a posteriori. Informative features should not be ignored, since they could be utilized to
help optimize the models that generate these semantic summaries in the first place.
In this research, we adopt a leave-one-out approach to assess the impact of various
features on the quality of automatically generated summaries that contain structured background
knowledge. We first create the gold standard summaries, using information-theoretic
methods, by extraction and validation, then the semantic summaries are transformed into
an equivalent textual format. Finally, various similarity metrics, such as cosine similarity,
euclidean distance, and Jensen-Shannon divergence are computed under different feature
combinations, to assess summary quality against the textual gold standard. We report on
the relative importance of the various features used to automatically generate the semantic
summaries in a biomedical application. Our evaluation suggests that the proposed approach
is an effective automatic
Continuous Exposure to Chrysotile Asbestos Can CauseGhazal Khan
This document summarizes a study that found continuous exposure to chrysotile asbestos can induce transformation of human mesothelial cells through signaling of HMGB1 and TNF-α, similar to effects of crocidolite asbestos exposure. Both asbestos types induced epithelial-to-mesenchymal transition in cells, characterized by downregulation of E-cadherin and phosphorylation/nuclear translocation of β-catenin. While crocidolite exposure induced sustained gene expression changes and HMGB1 release, chrysotile effects returned to baseline within 5-8 weeks. Continuous chrysotile exposure was required to maintain elevated HMGB1 levels, supporting the role of fiber persistence in biological activity.
Opening remarks on IO in 1st-Line NSCLCMauricio Lema
This document discusses immune-oncology and its role as a new paradigm for first-line treatment of non-small cell lung cancer (NSCLC). It provides a brief history of developments in immunotherapy including checkpoint inhibitors like pembrolizumab. Clinical trials results are presented showing that combining pembrolizumab with chemotherapy improves overall survival across all PD-L1 expression levels for both non-squamous and squamous NSCLC. The document concludes that immune checkpoint blockade is transforming NSCLC treatment.
The document describes a study that identified distinct methylation subtypes of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) using genome-wide DNA methylation data. Four subtypes were identified with high (HM), intermediate (IM), low (LM), or minimal (MM) levels of methylation. The subtypes showed differences in epigenetically silenced genes and frequencies of genetic alterations. Specifically, the HM subtype was enriched for ERBB2 alterations and ARID1A mutations. The findings suggest etiological and biological differences between the subtypes that could help direct clinical care.
Zauderer, M.G., et al. Clinical Cancer Research, 2017.sellasq4
1. This randomized phase II trial evaluated the WT1 peptide vaccine galinpepimut-S combined with GM-CSF and Montanide in patients with malignant pleural mesothelioma after multimodality therapy.
2. The trial randomized 41 patients to galinpepimut-S plus adjuvants or adjuvants alone. The control arm was stopped early due to a futility analysis showing progression within 1 year in over 10 of the first 20 patients.
3. Trends toward improved progression-free survival (10.1 vs 7.4 months) and overall survival (22.8 vs 18.3 months) were observed in the vaccine arm compared to control, but the trial was
Autism & Related Disabilities is a developmental disorder that affects the brain's normal development of social and communication skills. It is also known as a complex developmental disability. Austin Journal of Autism & Related Disabilities is an open access, peer reviewed scholarly journal committed to publication of unique contributions concerned with Autism & Related Disabilities.
Austin Journal of Autism & Related Disabilities accepts original research articles, review articles, case reports, clinical images and rapid communication on all the aspects of Autism & Related Disabilities.
EHA poster Genomic Analysis by MyAML with ChemotherapySuzanne M. Graham
1. This study analyzed genomic mutations from 24 AML patient samples using MyAML sequencing and correlated the mutation data with in vitro drug sensitivity profiles to identify associations between specific mutations and drug responses.
2. On average, each sample exhibited 129 missense mutations and over 12 coding insertions/deletions identified by MyAML.
3. Statistical analysis revealed several significant correlations between individual gene mutations and chemotherapy drug sensitivities, though further validation is still needed. The aim is to determine if genomic data can help predict optimal drug treatments for AML patients.
- Immunotherapy with checkpoint inhibitors such as nivolumab has shown superior efficacy compared to docetaxel chemotherapy in previously treated advanced non-small cell lung cancer (NSCLC) based on results from randomized clinical trials.
- In the CheckMate 017 trial of pretreated squamous NSCLC, nivolumab demonstrated a median progression-free survival of 3.5 months compared to 2.8 months for docetaxel, as well as improved 1-year progression-free survival rates.
- These results established nivolumab and other immune checkpoint inhibitors as new standard treatment options for patients with advanced NSCLC who have progressed on previous chemotherapy.
Cómo funciona la inmunoterapia antineoplásicaMauricio Lema
This document summarizes the mechanisms of immunotherapy. It discusses how immunotherapy works to boost the immune system's ability to detect and destroy cancer cells by overcoming tumor-induced immunosuppression. Key discoveries discussed include CTLA-4 as an immune checkpoint protein inhibited by ipilimumab, and PD-1 and its ligands inhibited by drugs like nivolumab and pembrolizumab. The roles of scientists like James Allison, Tasuku Honjo, and mechanisms of therapies like CAR T-cell therapy are summarized.
1) The study examines the molecular interaction between an autoreactive T cell receptor (TCR) expressed by a CD8+ T cell clone (1E6) and its target, a human leukocyte antigen HLA-A*0201 complexed with a glucose-sensitive preproinsulin peptide (A2-ALW).
2) Functional tests confirmed the 1E6 clone efficiently kills human islet beta cells in a HLA-A*0201-restricted manner.
3) Biophysical analysis revealed the 1E6 TCR binds the A2-ALW complex with extraordinarily weak affinity, around 278 μM, much lower than typical pathogen-specific TCR-pMHC interactions in the 1-10
This presentation summarizes data related to the CAR-T cell technology and its potential application for cancer therapy. This oral presentation was presented at the 39th PAMM winter meeting in Roma the 8th f February 2018 by Eric Raymond
This presentation contains all the updated information regarding ongoing treatment protocol, HSCT, Antibiotic prophylaxis, upcoming targeted therapies related to AML
maintrac liquid biopsy on circulating epithelial tumor cells Peter Pachmann
This document summarizes a study on monitoring the response of circulating epithelial tumor cells (CETCs) to adjuvant chemotherapy in breast cancer patients. The study found that CETCs can be quantified from blood samples of patients before, during, and after chemotherapy. Three typical response patterns were observed: a decrease of more than 10-fold in CETC numbers correlated with a good prognosis; marginal changes in CETC numbers correlated with a medium prognosis; and an increase of more than 10-fold in CETC numbers, even after an initial decrease, correlated with a poor prognosis and high risk of early relapse. Patients with increasing CETC numbers had a significantly worse relapse-free survival compared to the other groups. Therefore,
This document discusses transarterial therapies for the treatment of intrahepatic cholangiocarcinoma (ICC), a rare but devastating cancer. It reviews the current evidence for chemoembolization and radioembolization in treating ICC. Several studies show that chemoembolization, using various chemotherapy regimens with or without drug-eluting beads, can provide median survival rates of 9-23 months for unresectable ICC. Emerging evidence also supports the potential role of radioembolization, but further research is still needed. Overall, transarterial therapies may help improve outcomes for ICC when surgery is not possible.
Chemotherapy in ca urinary bladder dr prasanta dashPrasanta Dash
This document discusses chemotherapy options for metastatic bladder cancer. It notes that the prognosis remains poor with a median survival of 14 months. It reviews response rates of single agents like cisplatin, methotrexate, and doxorubicin. It then discusses combination regimens like MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin), noting response rates of around 50% and median survival of approximately 12 months based on several studies. Larger phase 3 trials found MVAC improved median survival compared to cisplatin or cisplatin/cyclophosphamide regimens.
Cancer Precision Medicine Physiological Function of C MYC as Targeted Moleculeijtsrd
The genome represents a design for creating the body, with each one being different. In cancer genomic medicine, many genes are simultaneously examined using mainly cancer tissues the oncogene panel test , and gene mutations are revealed. Cancer treatments are then initiated according to each individual's constitution and medical condition based on gene mutations. A system for cancer genome medical treatment is currently being developed. In the treatment of several cancer types, the "oncogene test with an oncogene companion diagnosis" is already being performed as a standard test using cancer tissue to detect one or several gene mutations. Precision Medicine discovering unique therapies that treat an individual's cancer based on the specific abnormalities, i.e. germline or somatic mutations of their tumors. In this paper, we will explain the biological role of C MYC and emphasize the importance of C MYC as a target factor in cancer precision medicine. The functional activated C MYC for cell proliferation and tumorigenesis is potential candidate as anti oncogenic molecule. Takuma Hayashi | Ikuo Konishi "Cancer Precision Medicine: Physiological Function of C-MYC as Targeted Molecule" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-5 , August 2019, URL: https://www.ijtsrd.com/papers/ijtsrd28030.pdfPaper URL: https://www.ijtsrd.com/medicine/other/28030/cancer-precision-medicine-physiological-function-of-c-myc-as-targeted-molecule/takuma-hayashi
Modeling the Dynamics of Glioblastoma Multiforme and Cancer Stem CellsStephen Steward
In this talk, we extend the work of Kronik, Kogan, Vainstein, and Agur (2008) by incorporating the cancer stem cell hypothesis into a treatment model for Glioblastoma Multiforme. Cancer Stem Cells (CSCs) are a specialized form of tumor cell with normal adult stem cell properties. CSCs are believed to be one of the primary reasons for cancer recurrence since they are more resilient to current treatment practices and are able to repopulate the tumor. We present a system of nonlinear ordinary differential equations that describes the interaction between cancer stem cells, tumor cells, and alloreactive cytotoxic-T-lymphocytes (CTLs). Under the assumption of constant treatment, we present conditions on the treatment amount that leads to a locally stable cure state. We also explore a more biologically accurate treatment schedule in which CTLs are injected periodically. In the case of periodic treatment, we numerically establish treatment schedules that lead to cancer persistence, cancer recurrence, and cancer eradication. We conclude with a sensitivity analysis of our parameters and a discussion of biological implications.
This document summarizes research on anaplastic large cell lymphoma (ALCL) associated with breast implants. The researchers established three new cell lines from patient biopsy specimens to study the unique biology of this cancer. Characterization found chromosomal abnormalities but no common genetic translocations. The cancer cells showed markers of T-cells and antigen presentation. Studies revealed strong activation of STAT3 signaling related to increased interleukin-6 and decreased SHP-1 phosphatase, suggesting a mechanism of cell survival. Inhibiting STAT3 or treating with chemotherapy killed the cancer cells in vitro, indicating potential new therapies for this disease. The cell lines provide models to further understand breast implant-associated ALCL and identify effective treatments.
Guidelines for the prescribed activity for 131I remnant ablation on different...Michael
This document summarizes and compares guidelines from seven professional organizations - ATA, ESMO, BTA, NCCN, SNM, EANM, CSE - regarding the prescribed radioactive iodine (131I) activity for remnant ablation in patients with differentiated thyroid cancer. Most guidelines recommend 30-100 mCi. However, the objectives and definitions vary - ablation is defined as eliminating thyroid remnant by some, but may also treat microscopic tumors by others. Two recent randomized controlled trials found that 30 mCi was as effective as 100 mCi for ablation, with fewer side effects. Successful ablation can be achieved with as little as 30 mCi according to these studies and ATA guidelines.
Nigella sativa bioactives against Non-Small Cell Lung Cancer & Breast CancerYusuf Asad
This document summarizes a study on targeting the ERK and AKT pathways in non-small cell lung cancer and triple-negative breast cancer cells with bioactives from Nigella sativa. The study found that thymoquinone (TQ) and thymol (THY) from N. sativa exhibited cytotoxic effects on cancer cells in a dose-dependent manner. Combining THY and TQ showed greater inhibition of cell viability than either component alone. Treatment with the combination also significantly downregulated expression of the AKT and ERK genes involved in proliferation. The findings suggest TQ may improve the efficacy of THY as an adjuvant therapy for lung and breast cancers.
Critical Role of PET-Scan in Unravelling the Dual Pathology- Review of Litera...AnonIshanvi
Simultaneous presentation of two lymphatic haematological malignancies is extremely rare. Adequate and optimal diagnostic steps including various imaging techniques and histopathological biopsies are required unpin the exact diagnoses to be able to deliver the best management strategies
Critical Role of PET-Scan in Unravelling the Dual Pathology- Review of Litera...daranisaha
Simultaneous presentation of two lymphatic haematological malignancies is extremely rare. Adequate and optimal diagnostic steps including various imaging techniques and histopathological biopsies are required unpin the exact diagnoses to be able to deliver the best management strategies...
Critical Role of PET-Scan in Unravelling the Dual Pathology- Review of Litera...JohnJulie1
Simultaneous presentation of two lymphatic haematological malignancies is extremely rare. Adequate and optimal diagnostic steps including various imaging techniques and histopathological biopsies are required unpin the exact diagnoses to be able to deliver the best management strategies...
Critical Role of PET-Scan in Unravelling the Dual Pathology- Review of Litera...NainaAnon
This document presents a case report of a rare occurrence of simultaneous diffuse large B-cell lymphoma (DLBCL) and multiple myeloma in a 70-year-old man. Positron emission tomography/computed tomography (PET/CT) scanning revealed discrepancies in fluorodeoxyglucose (FDG) uptake between myelomatous bone lesions and an inguinal lymph node. Biopsy of the lymph node confirmed DLBCL. The case highlights the important role of PET/CT scanning in determining the optimal biopsy site when evaluating patients for potential dual hematological malignancies. PET/CT scanning can help guide diagnosis and treatment planning in these complex cases.
Autism & Related Disabilities is a developmental disorder that affects the brain's normal development of social and communication skills. It is also known as a complex developmental disability. Austin Journal of Autism & Related Disabilities is an open access, peer reviewed scholarly journal committed to publication of unique contributions concerned with Autism & Related Disabilities.
Austin Journal of Autism & Related Disabilities accepts original research articles, review articles, case reports, clinical images and rapid communication on all the aspects of Autism & Related Disabilities.
EHA poster Genomic Analysis by MyAML with ChemotherapySuzanne M. Graham
1. This study analyzed genomic mutations from 24 AML patient samples using MyAML sequencing and correlated the mutation data with in vitro drug sensitivity profiles to identify associations between specific mutations and drug responses.
2. On average, each sample exhibited 129 missense mutations and over 12 coding insertions/deletions identified by MyAML.
3. Statistical analysis revealed several significant correlations between individual gene mutations and chemotherapy drug sensitivities, though further validation is still needed. The aim is to determine if genomic data can help predict optimal drug treatments for AML patients.
- Immunotherapy with checkpoint inhibitors such as nivolumab has shown superior efficacy compared to docetaxel chemotherapy in previously treated advanced non-small cell lung cancer (NSCLC) based on results from randomized clinical trials.
- In the CheckMate 017 trial of pretreated squamous NSCLC, nivolumab demonstrated a median progression-free survival of 3.5 months compared to 2.8 months for docetaxel, as well as improved 1-year progression-free survival rates.
- These results established nivolumab and other immune checkpoint inhibitors as new standard treatment options for patients with advanced NSCLC who have progressed on previous chemotherapy.
Cómo funciona la inmunoterapia antineoplásicaMauricio Lema
This document summarizes the mechanisms of immunotherapy. It discusses how immunotherapy works to boost the immune system's ability to detect and destroy cancer cells by overcoming tumor-induced immunosuppression. Key discoveries discussed include CTLA-4 as an immune checkpoint protein inhibited by ipilimumab, and PD-1 and its ligands inhibited by drugs like nivolumab and pembrolizumab. The roles of scientists like James Allison, Tasuku Honjo, and mechanisms of therapies like CAR T-cell therapy are summarized.
1) The study examines the molecular interaction between an autoreactive T cell receptor (TCR) expressed by a CD8+ T cell clone (1E6) and its target, a human leukocyte antigen HLA-A*0201 complexed with a glucose-sensitive preproinsulin peptide (A2-ALW).
2) Functional tests confirmed the 1E6 clone efficiently kills human islet beta cells in a HLA-A*0201-restricted manner.
3) Biophysical analysis revealed the 1E6 TCR binds the A2-ALW complex with extraordinarily weak affinity, around 278 μM, much lower than typical pathogen-specific TCR-pMHC interactions in the 1-10
This presentation summarizes data related to the CAR-T cell technology and its potential application for cancer therapy. This oral presentation was presented at the 39th PAMM winter meeting in Roma the 8th f February 2018 by Eric Raymond
This presentation contains all the updated information regarding ongoing treatment protocol, HSCT, Antibiotic prophylaxis, upcoming targeted therapies related to AML
maintrac liquid biopsy on circulating epithelial tumor cells Peter Pachmann
This document summarizes a study on monitoring the response of circulating epithelial tumor cells (CETCs) to adjuvant chemotherapy in breast cancer patients. The study found that CETCs can be quantified from blood samples of patients before, during, and after chemotherapy. Three typical response patterns were observed: a decrease of more than 10-fold in CETC numbers correlated with a good prognosis; marginal changes in CETC numbers correlated with a medium prognosis; and an increase of more than 10-fold in CETC numbers, even after an initial decrease, correlated with a poor prognosis and high risk of early relapse. Patients with increasing CETC numbers had a significantly worse relapse-free survival compared to the other groups. Therefore,
This document discusses transarterial therapies for the treatment of intrahepatic cholangiocarcinoma (ICC), a rare but devastating cancer. It reviews the current evidence for chemoembolization and radioembolization in treating ICC. Several studies show that chemoembolization, using various chemotherapy regimens with or without drug-eluting beads, can provide median survival rates of 9-23 months for unresectable ICC. Emerging evidence also supports the potential role of radioembolization, but further research is still needed. Overall, transarterial therapies may help improve outcomes for ICC when surgery is not possible.
Chemotherapy in ca urinary bladder dr prasanta dashPrasanta Dash
This document discusses chemotherapy options for metastatic bladder cancer. It notes that the prognosis remains poor with a median survival of 14 months. It reviews response rates of single agents like cisplatin, methotrexate, and doxorubicin. It then discusses combination regimens like MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin), noting response rates of around 50% and median survival of approximately 12 months based on several studies. Larger phase 3 trials found MVAC improved median survival compared to cisplatin or cisplatin/cyclophosphamide regimens.
Cancer Precision Medicine Physiological Function of C MYC as Targeted Moleculeijtsrd
The genome represents a design for creating the body, with each one being different. In cancer genomic medicine, many genes are simultaneously examined using mainly cancer tissues the oncogene panel test , and gene mutations are revealed. Cancer treatments are then initiated according to each individual's constitution and medical condition based on gene mutations. A system for cancer genome medical treatment is currently being developed. In the treatment of several cancer types, the "oncogene test with an oncogene companion diagnosis" is already being performed as a standard test using cancer tissue to detect one or several gene mutations. Precision Medicine discovering unique therapies that treat an individual's cancer based on the specific abnormalities, i.e. germline or somatic mutations of their tumors. In this paper, we will explain the biological role of C MYC and emphasize the importance of C MYC as a target factor in cancer precision medicine. The functional activated C MYC for cell proliferation and tumorigenesis is potential candidate as anti oncogenic molecule. Takuma Hayashi | Ikuo Konishi "Cancer Precision Medicine: Physiological Function of C-MYC as Targeted Molecule" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-5 , August 2019, URL: https://www.ijtsrd.com/papers/ijtsrd28030.pdfPaper URL: https://www.ijtsrd.com/medicine/other/28030/cancer-precision-medicine-physiological-function-of-c-myc-as-targeted-molecule/takuma-hayashi
Modeling the Dynamics of Glioblastoma Multiforme and Cancer Stem CellsStephen Steward
In this talk, we extend the work of Kronik, Kogan, Vainstein, and Agur (2008) by incorporating the cancer stem cell hypothesis into a treatment model for Glioblastoma Multiforme. Cancer Stem Cells (CSCs) are a specialized form of tumor cell with normal adult stem cell properties. CSCs are believed to be one of the primary reasons for cancer recurrence since they are more resilient to current treatment practices and are able to repopulate the tumor. We present a system of nonlinear ordinary differential equations that describes the interaction between cancer stem cells, tumor cells, and alloreactive cytotoxic-T-lymphocytes (CTLs). Under the assumption of constant treatment, we present conditions on the treatment amount that leads to a locally stable cure state. We also explore a more biologically accurate treatment schedule in which CTLs are injected periodically. In the case of periodic treatment, we numerically establish treatment schedules that lead to cancer persistence, cancer recurrence, and cancer eradication. We conclude with a sensitivity analysis of our parameters and a discussion of biological implications.
This document summarizes research on anaplastic large cell lymphoma (ALCL) associated with breast implants. The researchers established three new cell lines from patient biopsy specimens to study the unique biology of this cancer. Characterization found chromosomal abnormalities but no common genetic translocations. The cancer cells showed markers of T-cells and antigen presentation. Studies revealed strong activation of STAT3 signaling related to increased interleukin-6 and decreased SHP-1 phosphatase, suggesting a mechanism of cell survival. Inhibiting STAT3 or treating with chemotherapy killed the cancer cells in vitro, indicating potential new therapies for this disease. The cell lines provide models to further understand breast implant-associated ALCL and identify effective treatments.
Guidelines for the prescribed activity for 131I remnant ablation on different...Michael
This document summarizes and compares guidelines from seven professional organizations - ATA, ESMO, BTA, NCCN, SNM, EANM, CSE - regarding the prescribed radioactive iodine (131I) activity for remnant ablation in patients with differentiated thyroid cancer. Most guidelines recommend 30-100 mCi. However, the objectives and definitions vary - ablation is defined as eliminating thyroid remnant by some, but may also treat microscopic tumors by others. Two recent randomized controlled trials found that 30 mCi was as effective as 100 mCi for ablation, with fewer side effects. Successful ablation can be achieved with as little as 30 mCi according to these studies and ATA guidelines.
Nigella sativa bioactives against Non-Small Cell Lung Cancer & Breast CancerYusuf Asad
This document summarizes a study on targeting the ERK and AKT pathways in non-small cell lung cancer and triple-negative breast cancer cells with bioactives from Nigella sativa. The study found that thymoquinone (TQ) and thymol (THY) from N. sativa exhibited cytotoxic effects on cancer cells in a dose-dependent manner. Combining THY and TQ showed greater inhibition of cell viability than either component alone. Treatment with the combination also significantly downregulated expression of the AKT and ERK genes involved in proliferation. The findings suggest TQ may improve the efficacy of THY as an adjuvant therapy for lung and breast cancers.
Critical Role of PET-Scan in Unravelling the Dual Pathology- Review of Litera...AnonIshanvi
Simultaneous presentation of two lymphatic haematological malignancies is extremely rare. Adequate and optimal diagnostic steps including various imaging techniques and histopathological biopsies are required unpin the exact diagnoses to be able to deliver the best management strategies
Critical Role of PET-Scan in Unravelling the Dual Pathology- Review of Litera...daranisaha
Simultaneous presentation of two lymphatic haematological malignancies is extremely rare. Adequate and optimal diagnostic steps including various imaging techniques and histopathological biopsies are required unpin the exact diagnoses to be able to deliver the best management strategies...
Critical Role of PET-Scan in Unravelling the Dual Pathology- Review of Litera...JohnJulie1
Simultaneous presentation of two lymphatic haematological malignancies is extremely rare. Adequate and optimal diagnostic steps including various imaging techniques and histopathological biopsies are required unpin the exact diagnoses to be able to deliver the best management strategies...
Critical Role of PET-Scan in Unravelling the Dual Pathology- Review of Litera...NainaAnon
This document presents a case report of a rare occurrence of simultaneous diffuse large B-cell lymphoma (DLBCL) and multiple myeloma in a 70-year-old man. Positron emission tomography/computed tomography (PET/CT) scanning revealed discrepancies in fluorodeoxyglucose (FDG) uptake between myelomatous bone lesions and an inguinal lymph node. Biopsy of the lymph node confirmed DLBCL. The case highlights the important role of PET/CT scanning in determining the optimal biopsy site when evaluating patients for potential dual hematological malignancies. PET/CT scanning can help guide diagnosis and treatment planning in these complex cases.
Critical Role of PET-Scan in Unravelling the Dual Pathology- Review of Litera...semualkaira
Simultaneous presentation of two lymphatic haematological malignancies is extremely rare. Adequate and optimal diagnostic steps including various imaging techniques and histopathological biopsies are required unpin the exact diagnoses to be able to deliver the best management strategies...
Critical Role of PET-Scan in Unravelling the Dual Pathology- Review of Litera...semualkaira
Simultaneous presentation of two lymphatic haematological malignancies is extremely rare. Adequate and optimal diagnostic steps including various imaging techniques and histopathological biopsies are required unpin the exact diagnoses to be able to deliver the best management strategies...
The simultaneous occurrence of two lymphatic malignancies in
one patient is extremely rare with an incidence rate of 1.4–6.5
cases/1,000,000 individuals [8]. Co-existence of MM and other
lymphoid malignancies like Chronic Lymphocytic Leukemia (CLL)
[9], MM and Hodgkin’s Disease (HD) [10], MM and Lympho
Plasmacytic Lymphoma (LPL) [11] has been reported. However,
there are less than 5 reported cases in PubMed of simultaneous
presentation of DLBCL and MM
Critical Role of PET-Scan in Unravelling the Dual Pathology- Review of Litera...EditorSara
This document presents a case report of a rare occurrence of simultaneous diffuse large B-cell lymphoma (DLBCL) and multiple myeloma in a 70-year-old male patient. Positron emission tomography/computed tomography (PET/CT) imaging revealed discrepancies in fluorodeoxyglucose (FDG) uptake between myelomatous bone lesions and an inguinal lymph node. Biopsy of the lymph node confirmed DLBCL. The case highlights the critical role of PET/CT in determining the optimal biopsy site and unraveling the dual pathology. It also discusses the rarity and complex treatment considerations of concurrent lymphoid malignancies.
Similar to CDAC 2018 Angaroni optimal control (20)
This document summarizes a paper that presents a new tool called Simulated Annealing Single Cell (SASC) for inferring cancer progression from single-cell sequencing data. SASC allows for the loss of mutations, which violates the common assumption that mutations cannot occur in the same location. SASC uses simulated annealing, a heuristic technique, to search for maximum likelihood trees representing cancer evolution. It was shown to accurately infer ancestor-descendant mutation relationships and detect mutation losses on both simulated and real single-cell sequencing data, outperforming existing tools that do not allow for mutation loss. The paper concludes that SASC provides an improved model for analyzing intra-tumor heterogeneity from single-cell data.
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CDAC 2018 Angaroni optimal control
1. Optimal Control of chronic myeloid leukemia treatment
F.Angaroni
May 24, 2018
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 1 / 36
2. 1 The disease
Differential equations model
2 Optimal control
Analytic solution: the Pontryagins maximum principle
Numerical solution: the Pontryagins maximum principle
Optimal control: the CML therapy examples
Optimal control: the CML therapy
3 Future works
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 1 / 36
3. The disease: Mathematical hypothesis
This disease is driven by the BRC-ABL oncogene.
Since BCR-ABL mutation is present in all leukemic cells the ratio of
cancer cells respect to healthy cells is a ”simple” measurements.
About 2000 follow up could be found in literature. Their are an
example of measurements of the in vivo kinetics (F.Michor)
Exponential decay of cancer cells, and exponential blast after the stop
of the therapy, tell us that N(t) should be an exponential (solution of
first order differential equation) or described by a Poisson process.
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 2 / 36
4. The disease: Mathematical hypothesis
We divide the cells of the tiusse under study in ne non intersecting
ensambles, every ensamble represents a certain stage of cell differentiation.
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 3 / 36
5. Compartments Model
In this case, we divide the cells in
four ensambles:
1 Stem cells (SC)
2 Precursors Cells (PC)
3 Differentiated cells (PC)
4 Terminally differentiated cells
(TD)
Every collection of these ensembles
is a branch.
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 4 / 36
6. Differential equations model
Since BCR-ABL mutation is present in all leukemic cells we can distinguish
between
Healthy branch
Leukemic branch
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 5 / 36
7. Differential equations model
We attach a function ci,l (t) to every ensemble, it represents the number
of cells in one ensemble.
We will study transition rate between classes.
Given the following parameters:
pi,k the division rate of the cells
di,k the death rate of the cells
ai,k ∈ [0, 1] the probability of self-renewal
λ the probability for unit of time for a SC to develop the mutation
s(t) = 1
1+k( 4
i=1
h
j=l ci,j (t))
biochemical signal that regulate the cells
proliferation, it depends only on the number of mature cells
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 6 / 36
8. Differential equations model
Considering only symmetric differentiation, the transition rate for the ci,k
ensamble are:
+2pi,kai,kci (t)s(t) a in-going flux caused by the replication, this
contribute is absent for the TD ensembles,
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 7 / 36
9. Differential equations model
Considering only symmetric differentiation, the transition rate for the ci,k
ensamble are:
+s(t)pi−1,k(1 − ai−1,k)ci−1,k(t) a in-going flux due to the
differentiation in the previous ensemble of the branch, it is not present
for the SC (i = 1)
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 8 / 36
10. Differential equations model
Considering only symmetric differentiation, the transition rate for the ci,k
ensamble are: :
−di,kci,k out-going flux due to the death of cells,
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 9 / 36
11. Differential equations model
Considering only symmetric differentiation, the transition rate for the ci,k
ensamble are:
−s(t)pi ci (t) out-going flux due to the differentiation,
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 10 / 36
12. Differential equations model
Considering only symmetric differentiation, the transition rate are give by:
λc1,k in-going flux for c1,k+1 and out-going flux for c1,k. It represents
the generation of the tumor SC from the healthy SC.
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 11 / 36
14. Differential equations model
This tumor has a molecularly targeted therapy: Imatinib an inhibitor of
BCR-ABL gene.
The therapy is simulate as a decrease of 3 order of magnitude of division
rate of tumoral cells.
Figure: From:Dynamics of chronic myeloid leukemia F.Michor et al.
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 13 / 36
15. Differential equations model
The model is in a good agreement with the experimental data,
defining a figure of merit (FOM)
T(t) =
4
i=1 ci,l (t)
4
i=1
h
k=l ci,k(t)
. (2)
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 14 / 36
16. Differential equations model
The model presents a steady state where the tumoral stem cells are
constant: life-long disease.
c∗
1,l =
λc∗
1,h
(2a1,h − 1)p1,hs∗ − d1,l
, (3)
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 15 / 36
17. Differential equations model
The steady state is present only if:
d1,l c∗
1,l = [(2a1,l − 1)p1,l s∗
)]c∗
1,l + λc∗
1,h (4)
An early estimation of parameters could help in clinical management
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 16 / 36
18. Optimal control: motivation
The therapy has several drawbacks:
1 Fails in eradicating disease
Figure: From:Dynamics of chronic myeloid leukemia F.Michor et al.
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 17 / 36
19. Optimal control: motivation
The therapy has several drawbacks:
1 Fails in eradicating disease
2 Too expensive to be effective in a epidemiology contest
Figure: From:The price of drugs for chronic myeloid leukemia (CML) is a
reflection of the unsustainable prices of cancer drugs: from the perspective of a
large group of CML experts
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 18 / 36
20. Optimal control: motivation
The therapy has several drawbacks:
1 Fails in eradicating disease
2 Too expensive to be effective in a epidemiology contest
3 Is a life-long therapy (?)
Figure: From:Early molecular response and female sex strongly predict stable
undetectable BCR-ABL1, the criteria for imatinib discontinuation in patients with
CML
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 19 / 36
21. Optimal control: motivation
The therapy has several drawbacks:
1 Fails in eradicating disease
2 Too expensive to be effective in a epidemiology contest
3 Is a life-long therapy (?)
4 The therapy fails in approximately 15 − 25% of patients due to the
presence of resistant subclones, but Pharmacologic inhibitors for
imatinib-resistant CML exist and dose escalation can improve the
response in a subset of patients with resistance to standard dose
imatinib
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 20 / 36
22. Control Theory
Control Theory deals with systems that can be controlled, i.e. whose
evolution can be influenced by some external agent described by
u ∈ U ⊆ Rn, e.g.:
dx
dt
= f (x, u) (5)
There are two classes of control:
1 Open loop. Choose u as function of time t,
2 Closed loop or Feedback. Choose u as function of space variable x
Optimal control belongs to the first class.
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 21 / 36
23. Open loop control: the problem
Given the dynamics:
dx
dt
= f (x, u) (6)
T is the ensemble of final possible state x(T) at time t = T, if
x(0) = x0
L(x(t), u)dt is the running cost
φ(x(T)) is the pay-off
the optimal control problem is to find u∗(t) such that:
min[φ(x(T)) +
t
0
dtL(x(t), u(t))] x(0) = x0 x(T) ∈ T (7)
One approach to the optimal problem is the maximum principle :
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 22 / 36
24. Optimal control: Pontryagins Maximum Principle
The cornerstone of optimal control is the Pontryagins maximum
principle.
If u∗(t) and x∗(t) are optimal optimal solution and H(t, x(t), u(t), λ(t)) is
an Hamiltonian defined as follows:
H(t, x(t), u(t), λ(t)) = λf (t, u(t), x(t)) + L(u(t), x(t)) (8)
then there exists a piecewise differentiable adjoint variable λ(t) such that:
dλ(t)
dt
= −
∂H(t, x(t), u(t), λ(t))
dx
(9)
λ(T) = φ(x(T)) (10)
H(t, x∗
(t), u(t), λ(t)) ≤ H(t, x∗
(t), u∗
(t), λ(t)) (11)
with
∂H
∂u u=u∗
= 0 (12)
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 23 / 36
25. Optimal control: Numerical solution
Consider an optimal control system:
1) Cost
max φ(x(T)) +
T
t0
L(t, x(t), u(t))dt (13)
2) Dynamics
x(t0) = a
dx(t)
dt
= f (t, x(t), u(t)) (14)
3) The dynamics of the adjoint
λ(T) = φ(x(T))
dλ
dt
= −
∂H
∂x
(15)
4) Characterization of the optimal control
∂H
∂u u=u∗
= 0 (16)
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 24 / 36
26. Numerical solution: Forward-Backward Sweep Method
A rough outline of the algorithm to solve the optimal control problem is
the following:
1 Make an initial guess for u over the interval.
2 Solve Forward in time the Dynamics:
x(t0) = a
dx(t)
dt
= f (t, x(t), u(t)) (17)
3 Solve Backward in time the dynamics of the adjoint:
λ(T) = φ(x(T))
dλ
dt
= −
∂H
∂x
(18)
4 Update u using λ(t) and x(t) into the characterization of the
optimal control
∂H
∂u u=u∗
= 0 (19)
5 Check convergence. If values of the variables in this iteration and the
last iteration are negligibly close, output the current values as
solutions. If values are not close, return to Step 2.
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 25 / 36
28. Optimal control: the CML therapy
Where the control is given by:
U = {u(t)|∀t, 1 ≤ u(t)≤103}; (21)
We use the following cost:
C(t, x(t), u(t)) =
T
0
dt{Au2
(t) + B
4
i=1
c2
i,l (t)} (22)
where:
A economic cost per dose
u(t) is the control,
B 4
i=1 c2
i,l represents a running cost that depends on the size of the
tumor
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 27 / 36
29. Optimal control: the CML therapy
We define an Hamiltonian:
H = Au(t)2
+ B
4
i=1
c2
i,l (t) +
4
i=1
h
k=l
λi,k
dc1,k(t)
dt
(23)
We have 8 adjoint equation:
dλi,k
dt
= −
∂H
∂ci,h
i = 1, 2, 3, 4 k = l, h
and the characterization of the optimal control:
0 = −2Au(t) + log(u(t))(2a1,l − 1)p1,l s(t)c1,l +
+ log(u(t))(2(1 − a1,l )p1,l c1,l (t) + (2a2,l − 1)p2,l s(t)c2,l (t)))+
+ log(u(t))2(1 − a2,l )p2,l s(t)c2,l
(24)
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 28 / 36
30. Optimal control: the CML therapy
The Greedy controller (A = 100, B = 0 =⇒ u(t) = 1)
150 200 250 300
-4
-3
-2
-1
0
1
2
t (days)
Log[T]+2
150 200 250 300
0
2000
4000
6000
8000
10000
t (days)
cost
The Careful controller (A = 0, B = 1 =⇒ u(t) = 103)
150 200 250 300
-4
-3
-2
-1
0
1
2
t (days)
Log[T]+2
150 200 250 300
0
5.0×1014
1.0×1015
1.5×1015
t (days)
cost
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 29 / 36
31. Optimal control: the CML therapy
Problems:
the optimal solution exists and it is unique only for certain costs
Optimal control solutions implies continuous measurements and
action on the system: Optimal control is very complicated to apply to
a real system,
Since the functional space is very rich compared to a “discrete” space
the optimal control gives the upper bond of a decision process and
could be used to evaluate the sustainability of a therapy
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 30 / 36
32. Therapy control: future works
Using a random optimizer:
1 Consider the real pharmacodynamics and pharmacokinetics
Figure: From:Pharmacokinetics and pharmacodynamics of dasatinib in the chronic
phase of newly diagnosed chronic myeloid leukemia
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 31 / 36
33. Therapy control: future works
Using a random optimizer:
1 Consider the real pharcodynamics
2 Consider a more realistic cost, not quadratic
C(t, x(t), u(t)) =
T
0
dt{Ad(u) + Bd(u) + D
4
i=1
ci,l (t)} (25)
where:
d(u) the function that represent the dosage of the molecular therapy,
A economic cost per dose, B quality of life cost per dose (toxicity)
D 4
i=1 ci,l (t) represents a cost that depends on the number of
leukemic cells
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 32 / 36
34. Therapy control: future works
Using a random optimizer:
1 Consider the real pharcodynamics
2 Consider a more realistic cost
3 Consider a resistant branch and then manage the switch of the
therapy
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 33 / 36
35. Therapy control: future works
Using a random optimizer:
1 Consider the real pharcodynamics
2 Consider a more realistic cost
3 Consider a resistant branch and then manage the switch of the
therapy
4 Consider a discrete follow up
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 34 / 36
36. Therapy control: future works
Using a random optimizer:
1 Consider the real pharcodynamics
2 Consider a more realistic cost
3 Consider a discrete follow up
4 Consider resistant branch and then the switch of the therapy
5 Consider a hybrid therapy with “conventional“ radiotherapy or
chemotherapy with the aim of eradicate residual cancer stem cells
F.Angaroni (U. Bicocca) Optimal Control of the chronic myeloid leukemia treatment 23 May 2018 35 / 36
37. Thank you
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