CANCER DRUG PREVIEW PRESENTATION Challenges in Developing Preclinical Models of Hepatocellular Carcinoma Cedo Bagi, Senior Research Fellow, Pfizer, Inc.
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This is a conference presentation preview of the 7th Annual Cancer Drugs Research and Development Conference.
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The liver performs many important metabolic functions:
1) It plays a central role in carbohydrate, protein, and lipid metabolism, maintaining blood glucose levels and producing most plasma proteins.
2) Carbohydrate metabolism includes glycogen storage and gluconeogenesis to regulate blood sugar.
3) The liver manufactures many proteins including blood clotting factors, enzymes, and carrier proteins.
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Renal Tumour Angiomyolipoma - Bizarre Presentation
A 28-year old female presented with fever, chills, and flank pain. Imaging showed a large liver lesion initially thought to be a tumor or abscess. Further CT and MRI revealed the lesion to be retroperitoneal and connected to the upper pole of the right kidney. At surgery, 1.5 liters of pus was drained. Histopathology of the renal mass found it to be an angiomyolipoma, a rare renal tumor. Literature review discussed diagnostic challenges and optimal imaging techniques for diagnosing renal angiomyolipomas.
The pathway to uroradiology
1. MDCT uses a rotating X-ray tube and row of detectors to provide stronger X-rays than conventional CT. It can perform multiphase scans and multiplanar reconstructions.
2. MRI is useful for evaluating scrotal masses when ultrasound findings are discrepant, testicular involvement is diffuse, or fibrous lesions, lipomas or hemorrhage are suspected.
3. FDG-PET is limited in detecting localized prostate, bladder, and renal cancers due to low glycolytic activity of malignant cells and urinary excretion of FDG. However, it can help evaluate changes in tumor burden and site during and after therapy.
Tumors of kidney & urinary tract 2012
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RENAL TUMOURS
This document discusses renal tumours from the Department of Urology at Govt Royapettah Hospital and Kilpauk Medical College in Chennai. It provides an introduction to renal tumours and classifications. It describes various benign renal tumours including papillary adenoma, oncocytoma, angiomyolipoma and others. It also describes malignant renal cell carcinomas, including clear cell carcinoma, papillary renal cell carcinoma, chromophobe renal cell carcinoma and others. It discusses staging, histopathology, molecular markers and clinical presentation of renal tumours.
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Liver
The liver performs many important metabolic functions:
1) It plays a central role in carbohydrate, protein, and lipid metabolism, maintaining blood glucose levels and producing most plasma proteins.
2) Carbohydrate metabolism includes glycogen storage and gluconeogenesis to regulate blood sugar.
3) The liver manufactures many proteins including blood clotting factors, enzymes, and carrier proteins.
Transarterial radioembolization (tare)
TARE - TransArterial RadioEmbolization
interventional procedure with nuclear medicine
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Hematopoiesis
This document discusses hematology and hematopoiesis. It describes how blood cells are produced in the bone marrow from stem cells and progenitor cells that can differentiate into red blood cells, white blood cells, or platelets. The behavior of progenitor cells is regulated by the bone marrow microenvironment and hematopoietic growth factors. Growth factors bind to receptors on cells and influence cell differentiation through signal transduction pathways. In summary, the bone marrow produces blood cells through hematopoiesis driven by progenitor cells and growth factors.
Renal Tumour Angiomyolipoma - Bizarre Presentation
A 28-year old female presented with fever, chills, and flank pain. Imaging showed a large liver lesion initially thought to be a tumor or abscess. Further CT and MRI revealed the lesion to be retroperitoneal and connected to the upper pole of the right kidney. At surgery, 1.5 liters of pus was drained. Histopathology of the renal mass found it to be an angiomyolipoma, a rare renal tumor. Literature review discussed diagnostic challenges and optimal imaging techniques for diagnosing renal angiomyolipomas.
The pathway to uroradiology
1. MDCT uses a rotating X-ray tube and row of detectors to provide stronger X-rays than conventional CT. It can perform multiphase scans and multiplanar reconstructions.
2. MRI is useful for evaluating scrotal masses when ultrasound findings are discrepant, testicular involvement is diffuse, or fibrous lesions, lipomas or hemorrhage are suspected.
3. FDG-PET is limited in detecting localized prostate, bladder, and renal cancers due to low glycolytic activity of malignant cells and urinary excretion of FDG. However, it can help evaluate changes in tumor burden and site during and after therapy.
Tumors of kidney & urinary tract 2012
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Obesity induces changes to the gut microbiota and its metabolites that promote cellular senescence and a senescence-associated secretory phenotype (SASP) in hepatic stellate cells. This SASP facilitates the development of hepatocellular carcinoma (HCC) in mice. Specifically, a high-fat diet alters the gut microbiota to increase production of deoxycholic acid, which provokes SASP in hepatic stellate cells. This leads to proinflammatory cytokines and tumour-promoting factors that promote HCC upon exposure to a chemical carcinogen. Blocking deoxycholic acid production or depleting the gut microbiota reduced HCC development by decreasing senescent hepatic stellate cells.
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This document describes a case of a giant primary yolk sac tumor (YST) of the liver in a 39-year-old female patient. Imaging showed a large 25 cm solid heterogeneous mass in the right lobe of the liver as well as two smaller masses. The patient underwent right extended hepatectomy to remove the tumors. Pathology revealed the large mass was a YST. Primary YST of the liver is rare, and this case was notable for the giant size of the primary tumor as well as the presence of multifocal liver lesions. YST can be difficult to diagnose preoperatively due to similarities in imaging and serum markers with other liver tumors like hepatocellular carcinoma.
Circulating Endothelial Cells and Endothelial Progenitor Cells
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This document discusses various imaging modalities used to evaluate renal masses, including plain radiography, intravenous urography, ultrasound, computed tomography, magnetic resonance imaging, and renal arteriography. For each modality, it describes their utility in detecting and characterizing renal masses and differentiating renal cell carcinoma from other lesions. It also provides examples of imaging findings for various renal pathologies such as abscesses, cysts, angiomyolipomas, and others.
9 focal renal mass
This document discusses several renal masses that can be identified on clinical imaging. It provides examples of column of Bertin, renal cysts, renal cell carcinoma, Wilms' tumor, and renal hamartoma as seen on excretory urograms, nephrotomograms, renal scans, and arteriograms. Key imaging findings that help differentiate these masses include displacement of surrounding structures, density or vascularity of the mass, and characteristics of walls or borders. Differential diagnosis of renal masses is important for determining appropriate clinical management.
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Transarterial chemoembolization (TACE) involves delivering chemotherapy drugs and embolic agents directly into liver cancers via catheters in the hepatic artery. TACE is generally used to treat hepatocellular carcinoma that cannot be surgically removed. During the procedure, a catheter is placed into the hepatic artery supplying the tumor and chemotherapy mixed with iodinated oil is injected, followed by embolization of the artery with gelatin sponges. TACE can reduce tumor size and symptoms but common side effects include abdominal pain and nausea. Response to treatment is evaluated after 3-4 weeks using imaging to assess the extent of tumor coverage by the oil and residual enhancement.
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This document provides information on renal cell carcinoma (RCC), including epidemiology, risk factors, histologic subtypes, staging, clinical presentation, investigations, and management. RCC accounts for 2-3% of adult cancers. Clear cell RCC is the most common subtype. Presentation is often nonspecific, though flank pain, hematuria, and abdominal mass may occur. Imaging like CT and MRI are used to stage and characterize lesions. Treatment involves surgery (radical or partial nephrectomy) for localized disease. Up to 30% of patients experience relapse post-surgery.
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A 60-year-old male presented with painless hematuria and an abdominal lump. On examination, a palpable lump was found. Differential diagnoses included renal cell carcinoma (RCC), given the patient's age and presenting symptoms of hematuria and abdominal lump. RCC is the most common type of kidney cancer in adults. It typically presents in individuals aged 40-60 years and is more common in males. Risk factors include smoking and occupational exposures like asbestos. On pathology, RCC appears as a homogenous yellow mass replacing the renal parenchyma, with microscopically visible clear and dark cells lining blood vessels - explaining its early metastatic potential.
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This document discusses renal cell carcinoma in a 55-year-old male factory worker presenting with hematuria, loin pain, and a loin mass. It describes the patient's investigations, pathology findings of clear cell renal cell carcinoma, staging according to AJCC TNM classification, and treatment options including radical or partial nephrectomy depending on tumor size and extent. The prognosis is outlined with 5-year survival rates ranging from 65% for stage 1-2 disease to 10% for stage 4 metastatic renal cell carcinoma.
imaging in RCC
Ultrasound, CT, MRI, and PET scans are used to image renal cell carcinoma. Ultrasound has low sensitivity and specificity for detecting RCC. Color Doppler ultrasound and contrast-enhanced ultrasound can detect venous tumor thrombi and differentiate RCC from other masses. CT is more sensitive and specific and can assess tumor complexity using nephrometry scores. MRI is an alternative that is useful for smaller masses but carries risks for patients with kidney disease. PET scans have limited utility in RCC imaging. Staging requires determining tumor size, location and spread using the TNM system.
PATH610-Sheppard
The ureters demonstrate relative constrictions in three places:
- At the junction of ureters and renal pelves
- Where the ureters cross the brim of the pelvic inlet
- During their passage through the wall of the urinary bladder
These constricted areas are potential sites of obstruction by ureteric stones (calculi).
Liver fibrosis
Hepatic fibrosis is a reversible wound healing response characterized by the accumulation of extracellular matrix in the liver following chronic liver disease. The hepatic stellate cell is the principal cell involved in fibrogenesis, undergoing activation from a quiescent vitamin A storing cell to a proliferative, contractile myofibroblast that secretes extracellular matrix proteins. Assessment of fibrosis includes invasive liver biopsy as well as non-invasive markers and imaging. Treatment strategies target inhibiting liver injury, reducing inflammation, blocking hepatic stellate cell activation and proliferation, and modulating nuclear receptors involved in fibrosis. Several drugs are in clinical trials for treating hepatic fibrosis.
Renal lymphoma
Renal lymphoma can involve the kidneys through either primary or secondary spread. Imaging findings on CT scans commonly demonstrate multiple renal masses, a solitary mass, renal invasion from adjacent retroperitoneal disease, perirenal involvement, or diffuse renal infiltration. MRI findings are generally similar to CT, with lymphoma appearing as low signal intensity on T1-weighted images and isointense or moderately hyperintense on T2-weighted images, often with minimal contrast enhancement.
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Renal cell carcinoma
Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, originating from the lining of the proximal convoluted tubule. Risk factors include tobacco use, genetic factors, cystic kidney diseases, and exposure to certain chemicals. RCC is typically diagnosed through imaging tests and biopsy. Surgical removal of the kidney is the main treatment for localized RCC, while advanced or metastatic RCC may be treated with targeted drugs or immunotherapy. Prognosis depends on the stage, with localized RCC having high survival rates.
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Obesity induces changes to the gut microbiota and its metabolites that promote cellular senescence and a senescence-associated secretory phenotype (SASP) in hepatic stellate cells. This SASP facilitates the development of hepatocellular carcinoma (HCC) in mice. Specifically, a high-fat diet alters the gut microbiota to increase production of deoxycholic acid, which provokes SASP in hepatic stellate cells. This leads to proinflammatory cytokines and tumour-promoting factors that promote HCC upon exposure to a chemical carcinogen. Blocking deoxycholic acid production or depleting the gut microbiota reduced HCC development by decreasing senescent hepatic stellate cells.
10.1007_s11605-016-3123-1 YST
This document describes a case of a giant primary yolk sac tumor (YST) of the liver in a 39-year-old female patient. Imaging showed a large 25 cm solid heterogeneous mass in the right lobe of the liver as well as two smaller masses. The patient underwent right extended hepatectomy to remove the tumors. Pathology revealed the large mass was a YST. Primary YST of the liver is rare, and this case was notable for the giant size of the primary tumor as well as the presence of multifocal liver lesions. YST can be difficult to diagnose preoperatively due to similarities in imaging and serum markers with other liver tumors like hepatocellular carcinoma.
Circulating Endothelial Cells and Endothelial Progenitor Cells
Circulating endothelial cells (CEC) and endothelial progenitor cells (EPC) are markers of vascular damage and neovascularization, respectively. CEC detach from vessel walls during endothelial damage and reflect loss of vascular integrity, while EPC originate from bone marrow and contribute to new blood vessel formation. Both cell types are elevated in cancers and other diseases involving vascular dysfunction. CEC are mature endothelial cells in the blood indicating severe damage, whereas EPC are immature progenitor cells that promote neovascularization through differentiation into new endothelial cells. Together, CEC and EPC provide insights into vascular pathology and angiogenesis.
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This document presents a case report of a 54-year-old Egyptian woman found to have metastatic hepatocellular carcinoma (HCC) to the ovaries. Her initial presentation was an abdominal mass and elevated alpha-fetoprotein levels. Imaging revealed hepatic lesions and involvement of both ovaries. Histopathological examination of biopsy samples from the ovaries and liver showed features consistent with HCC. While rare, metastatic HCC should be considered in the differential diagnosis of hepatoid and oxyphil cell tumors of the ovary, especially in patients with risk factors for HCC such as hepatitis infection and cirrhosis. The case report reviews similar literature cases and discusses diagnostic criteria and distinguishing metastatic HCC from other potential ovarian tumors.
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The document discusses hematopoiesis, the process of blood cell production. It covers the discovery of hematopoietic stem cells, their development and migration during embryogenesis, and their residence in the bone marrow in adults. It also details the cytokines and growth factors that control hematopoiesis, including early-acting and later-acting factors. Additionally, it examines cytokine receptors, signaling pathways, transcription factors, and the hematopoietic microenvironment including the stem cell niche in the bone marrow.
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This document discusses various imaging modalities used to evaluate renal masses, including plain radiography, intravenous urography, ultrasound, computed tomography, magnetic resonance imaging, and renal arteriography. For each modality, it describes their utility in detecting and characterizing renal masses and differentiating renal cell carcinoma from other lesions. It also provides examples of imaging findings for various renal pathologies such as abscesses, cysts, angiomyolipomas, and others.
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This document discusses several renal masses that can be identified on clinical imaging. It provides examples of column of Bertin, renal cysts, renal cell carcinoma, Wilms' tumor, and renal hamartoma as seen on excretory urograms, nephrotomograms, renal scans, and arteriograms. Key imaging findings that help differentiate these masses include displacement of surrounding structures, density or vascularity of the mass, and characteristics of walls or borders. Differential diagnosis of renal masses is important for determining appropriate clinical management.
TACE- Transarterial Chemoembolisation
Transarterial chemoembolization (TACE) involves delivering chemotherapy drugs and embolic agents directly into liver cancers via catheters in the hepatic artery. TACE is generally used to treat hepatocellular carcinoma that cannot be surgically removed. During the procedure, a catheter is placed into the hepatic artery supplying the tumor and chemotherapy mixed with iodinated oil is injected, followed by embolization of the artery with gelatin sponges. TACE can reduce tumor size and symptoms but common side effects include abdominal pain and nausea. Response to treatment is evaluated after 3-4 weeks using imaging to assess the extent of tumor coverage by the oil and residual enhancement.
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This document discusses renal tumors based on a CT scan. It begins by describing the types of scans that can be used to evaluate renal tumors, with multislice CT scans being the most accurate test. It then outlines how to interpret CT scans to diagnose renal tumors based on enhancement and density measurements. Clinical presentations of renal tumors are provided, along with descriptions of paraneoplastic syndromes. Finally, treatment options for renal tumors via various types of nephrectomy are summarized.
Recent Advances:Hepatocellular Nodules
This document discusses various types of liver lesions including regenerative nodules, dysplastic nodules, hepatocellular adenoma, focal nodular hyperplasia, and hepatocellular carcinoma. It provides details on the histological and immunohistochemical features that can help differentiate these lesions. Key points include that dysplastic nodules are believed to be HCC precursors, hepatocellular adenomas can be single or multifocal and classified based on molecular features, and the distinction between well-differentiated HCC and hepatocellular adenoma can be challenging based on overlapping histological features alone.
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This document provides information on renal cell carcinoma (RCC), including epidemiology, risk factors, histologic subtypes, staging, clinical presentation, investigations, and management. RCC accounts for 2-3% of adult cancers. Clear cell RCC is the most common subtype. Presentation is often nonspecific, though flank pain, hematuria, and abdominal mass may occur. Imaging like CT and MRI are used to stage and characterize lesions. Treatment involves surgery (radical or partial nephrectomy) for localized disease. Up to 30% of patients experience relapse post-surgery.
Renal cell carcinoma
A 60-year-old male presented with painless hematuria and an abdominal lump. On examination, a palpable lump was found. Differential diagnoses included renal cell carcinoma (RCC), given the patient's age and presenting symptoms of hematuria and abdominal lump. RCC is the most common type of kidney cancer in adults. It typically presents in individuals aged 40-60 years and is more common in males. Risk factors include smoking and occupational exposures like asbestos. On pathology, RCC appears as a homogenous yellow mass replacing the renal parenchyma, with microscopically visible clear and dark cells lining blood vessels - explaining its early metastatic potential.
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This document discusses renal cell carcinoma in a 55-year-old male factory worker presenting with hematuria, loin pain, and a loin mass. It describes the patient's investigations, pathology findings of clear cell renal cell carcinoma, staging according to AJCC TNM classification, and treatment options including radical or partial nephrectomy depending on tumor size and extent. The prognosis is outlined with 5-year survival rates ranging from 65% for stage 1-2 disease to 10% for stage 4 metastatic renal cell carcinoma.
imaging in RCC
Ultrasound, CT, MRI, and PET scans are used to image renal cell carcinoma. Ultrasound has low sensitivity and specificity for detecting RCC. Color Doppler ultrasound and contrast-enhanced ultrasound can detect venous tumor thrombi and differentiate RCC from other masses. CT is more sensitive and specific and can assess tumor complexity using nephrometry scores. MRI is an alternative that is useful for smaller masses but carries risks for patients with kidney disease. PET scans have limited utility in RCC imaging. Staging requires determining tumor size, location and spread using the TNM system.
PATH610-Sheppard
The ureters demonstrate relative constrictions in three places:
- At the junction of ureters and renal pelves
- Where the ureters cross the brim of the pelvic inlet
- During their passage through the wall of the urinary bladder
These constricted areas are potential sites of obstruction by ureteric stones (calculi).
Liver fibrosis
Hepatic fibrosis is a reversible wound healing response characterized by the accumulation of extracellular matrix in the liver following chronic liver disease. The hepatic stellate cell is the principal cell involved in fibrogenesis, undergoing activation from a quiescent vitamin A storing cell to a proliferative, contractile myofibroblast that secretes extracellular matrix proteins. Assessment of fibrosis includes invasive liver biopsy as well as non-invasive markers and imaging. Treatment strategies target inhibiting liver injury, reducing inflammation, blocking hepatic stellate cell activation and proliferation, and modulating nuclear receptors involved in fibrosis. Several drugs are in clinical trials for treating hepatic fibrosis.
Renal lymphoma
Renal lymphoma can involve the kidneys through either primary or secondary spread. Imaging findings on CT scans commonly demonstrate multiple renal masses, a solitary mass, renal invasion from adjacent retroperitoneal disease, perirenal involvement, or diffuse renal infiltration. MRI findings are generally similar to CT, with lymphoma appearing as low signal intensity on T1-weighted images and isointense or moderately hyperintense on T2-weighted images, often with minimal contrast enhancement.
01. Hematopoiesis
Hematopoiesis is the formation of blood cells, including red blood cells, white blood cells, and platelets. It begins with pluripotent stem cells in the bone marrow that can differentiate into various blood cell types. The differentiation is regulated by hematopoietic growth factors and occurs through defined cellular pathways involving progenitor cells, precursors, and mature effector cells. Key growth factors include erythropoietin, which stimulates red blood cell production, and granulocyte colony-stimulating factor, which promotes granulocyte development.
Renal cell carcinoma
Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, originating from the lining of the proximal convoluted tubule. Risk factors include tobacco use, genetic factors, cystic kidney diseases, and exposure to certain chemicals. RCC is typically diagnosed through imaging tests and biopsy. Surgical removal of the kidney is the main treatment for localized RCC, while advanced or metastatic RCC may be treated with targeted drugs or immunotherapy. Prognosis depends on the stage, with localized RCC having high survival rates.
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Animal models like inbred mouse strains and techniques like adoptive transfer are useful for immunology research by reducing genetic variability. Inbred strains are genetically identical due to inbreeding, allowing the study of immune responses without interference from individual genetic differences. Adoptive transfer involves transferring lymphocytes from a donor mouse into an irradiated recipient mouse to study the immune response in isolation. SCID mice that lack mature immune cells accept grafts from other species, enabling the study of human immune system development within a mouse model through the use of SCID-human mice implanted with human tissues.
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This document provides an overview of animal models used in periodontal research. It discusses the definition and history of animal models, the need for animal models in periodontal research given limitations of human studies, and various categories and classifications of animal models. The document then examines specific animal models used in periodontal research, including rats, mice, and hamsters, describing their anatomy, how periodontal disease presents in each, and advantages and limitations of each model.
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Hepatocellular carcinoma is a primary cancer of the liver that is commonly associated with cirrhosis and hepatitis. Common causes include cirrhosis from various sources, chronic hepatitis B or C infection, and alcohol consumption. Symptoms can include abdominal pain, weight loss, jaundice, and nausea. Diagnosis involves imaging such as CT or MRI scans of the liver along with blood tests. Treatment options depend on factors like tumor size and liver function, and may include resection, transplantation, ablation, embolization, or chemotherapy. Prognosis can be assessed using scoring systems like the Child-Pugh score.
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2) Other potentially resectable isolated metastases, such as those in the lungs or peritoneum, may also be treated with surgery, providing 5-year survival rates around 20-40%.
3) Neoadjuvant chemotherapy can downsize initially unresectable liver metastases to make them resectable and improve long-term outcomes compared to surgery alone.
Renal cell carcinoma
A 60-year-old male presented with a 6-month history of blood in his urine, passing ribbon-like clots on two occasions with right flank pain radiating to his groin. He had weight loss and a previous investigation showed hypercalcemia. Imaging showed a hypoechoic solid mass in the right kidney cortex. The differential diagnosis includes renal cell carcinoma, the most common malignant tumor of the kidney in adults. Renal cell carcinoma originates in the renal cortex and presents with hematuria, flank pain, and weight loss. Staging investigations and surgery or other ablative techniques are used for treatment depending on the stage, with surveillance after for early detection of recurrence.
WHO CLASSIFICATION 2016 RENAL CELL CARCINOMA.pptx
The document summarizes updates to the 2016 WHO classification of renal cell carcinoma compared to the 2004 classification. Key changes include recognizing RCC as distinct subtypes based on histology, architecture, location, associated diseases and molecular alterations. The 2016 classification adds 9 new renal tumor entities, separates some subtypes, and groups familial and sporadic forms of RCC together. It provides greater specificity in RCC diagnosis and classification based on recent advances in understanding RCC pathogenesis and genetics.
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This document provides an overview of hematopoietic stem cell transplantation (HSCT). It defines hematopoietic stem cells and HSCT, and describes the types of transplants including autologous and allogenic. The key indications for each type are outlined. The process of HSCT is summarized, including donor selection, stem cell collection, cryopreservation, conditioning chemotherapy, stem cell infusion, and engraftment recovery. Post-transplant complications and supportive care measures are briefly discussed.
Benign tumors of the liver: Tumor like lesions
Benign tumors of the liver tumor like lesions that includes Mesenchymal hamartoma of the liver , focal fatty sparing and others
Principles of Oncology
This document discusses principles of oncology including cell number control, growth disorders, cancer classification, tumor spread and metastasis, stages of cancer, and an overview of carcinogenesis. It defines key terms like neoplasia, benign and malignant tumors, dysplasia, carcinoma and sarcoma. It also summarizes the hallmarks of cancer including self-sufficiency in growth signals, evasion of apoptosis, unlimited replicative potential, sustained angiogenesis, and genetic instability.
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This document summarizes the management of hepatocellular carcinoma (HCC). It discusses the incidence, biological markers, staging evaluations, and treatment options for HCC depending on the stage. For early stage disease (BCLC stages 0 and A), primary curative treatments include surgical resection or liver transplantation. For intermediate stage disease (BCLC stage B), locoregional therapies like radiofrequency ablation, microwave ablation, stereotactic body radiation therapy, and selective internal radiation therapy are options. For more advanced HCC (BCLC stages C and D), palliative treatments like transarterial chemoembolization or systemic therapies like sorafenib are utilized. SBRT is also explored as a bridge to liver transplantation
Hallmarks of cancer
The document discusses the hallmarks of cancer as proposed by Hanahan and Weinberg. It identifies the eight hallmarks as sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, deregulating cellular energetics, and avoiding immune destruction. It also discusses two enabling characteristics - genome instability and mutation, and tumor-promoting inflammation. Finally, it summarizes how several of these hallmarks, including sustaining proliferative signaling, activating invasion and metastasis, resisting cell death, and genome instability and mutation have been identified in breast cancer and contribute to its heterogeneity and treatment resistance.
Lymphoma
This document discusses the anatomy and functions of the lymphatic system and bone marrow. It describes that bone marrow is the site of blood cell production and has two types - red and yellow marrow. The lymphatic system includes lymph nodes, spleen, thymus, and mucosa-associated lymphoid tissue. Hodgkin's and non-Hodgkin's lymphoma are also discussed, including their causes, symptoms, diagnostic tests, and common treatment methods like chemotherapy and radiation therapy.
Ca kidney [edmond]
This document discusses kidney cancer (renal cell carcinoma). It covers the epidemiology, etiology, hereditary forms, VHL disease, histology, staging, diagnosis, and screening recommendations. Some key points:
1. RCC incidence is increasing with a peak age of 60-70. Risk factors include smoking, obesity, and family history. Clear cell RCC is the most common type.
2. VHL disease is a hereditary form associated with clear cell RCC and other tumors. It is caused by a defective VHL gene.
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Organs On Chips (OOC)
An organ-on-a-chip (OOC) is a multi-channel 3-D microfluidic cell culture chip that simulates the activities, mechanics and physiological response of entire organs and organ systems, a type of artificial organ
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paris presentation.pptx
The Paris System provides a standardized approach for reporting urinary cytology results with the aim of improving reproducibility and communication. It defines categories for negative, atypical urothelial cells, suspicious for high-grade urothelial carcinoma, and high-grade urothelial carcinoma based on nuclear and cytoplasmic features. Low-grade urothelial neoplasia requires the presence of three-dimensional clusters with fibrovascular cores. The system also provides guidance on specimen adequacy and the assessment of other malignancies and clinical management. Validation studies are still needed but the goal is to reliably detect high-grade urothelial neoplasia.
Liver biopsy
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1. Liver biopsy was first performed in the late 19th century and has since been refined and used more widely. It remains an important diagnostic and prognostic tool.
2. Liver biopsy indications include diagnosing liver disease when blood tests and imaging are inconclusive, assessing fibrosis stage and prognosis, and assisting treatment decisions.
3. The most common type is percutaneous biopsy, though transjugular and laparoscopic biopsies are also used. Percutaneous biopsy can be blind or imaged-guided.
4. Liver biopsy is generally safe but requires consideration of contraindications like coagulopathy,
Cancer biology.ppt
This document provides an overview of cancer biology and management. It discusses the epidemiology of cancer, noting that over 1.6 million new cancer diagnoses occur annually in the US. The most common causes of cancer death are lung, prostate, breast and colorectal cancers. It also describes the hallmarks of cancer at the cellular level, including uncontrolled growth, evasion of cell death, limitless replicative potential and metastasis. The diagnosis and staging of cancer is covered, as well as tumor markers, and surgical and chemotherapy approaches to management.
Introduction - Cellular Pathology 22-23(1).pptx
Here is a 1500 word response covering the requested short notes:
Carcinoma
Carcinoma is a type of cancer that arises from epithelial cells. Epithelial cells line the inner and outer surfaces of the body such as the skin, lung, breast, prostate etc. Carcinomas are classified based on the epithelial tissue they originated from and the characteristics of the cancer cells. The main types are squamous cell carcinoma, adenocarcinoma, small cell carcinoma and large cell carcinoma. Squamous cell carcinoma arises from squamous cells, which are flat, scale-like cells that form the surface of the skin. Lung cancer and cervical cancer are common examples. Adenocarcinoma originates from glandular
CA Prostate
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CANCER DRUG PREVIEW PRESENTATION Challenges in Developing Preclinical Models of Hepatocellular Carcinoma Cedo Bagi, Senior Research Fellow, Pfizer, Inc.
- 1. “Challenges in Developing Preclinical Models of Hepatocellular Carcinoma” Cedo Bagi M.D., Ph.D. Senior Research Fellow, GS&T San Diego, January, 2010
- 2. Challenges in Developing HCC Models 1. Importance of the liver in pharmaceutical sciences 2. Management of primary liver tumors and metastases of other tumors to the liver are huge clinical problem Xenograft and orthotopic models Biomarkers and imaging Liver vasculature: Implications for tumor growth and tumor metastases to liver Drug administration and tumor targeting HCC cell lines and liver biopsies Need for combination therapies Chimeric mice models (humanized liver models) HBV/HCV and HCC models 2
- 3. Xenograft and Orthotopic HCC Models • Body weight • Caliper • AFP • Human albumin • Liver function and • Serum chemistry • Histology • Histochemstry • IVIS imaging • Ultrasound • X-ray + contrast • MRI/PET 3
- 4. Liver vasculature - Implication for tumor growth and metastases • Importance of functional and nutritional vasculature for liver function; Tumor vasculature • Theories behind tumor growth and metastases • seed and soil • anatomical • mechanical • haemodynamic • Basic lobular architecture - Blood flows from the portal tract into the hepatic sinusoids and leaves the lobule via the terminal (“central”) venule central vein -3 1 es 3 z on 2 central vein 1 portal triad portal triad 4
- 5. Liver vasculature - Implication for tumor growth and metastases Flow distribution • total liver blood flow represents approximately 25% of the cardiac output (1500ml/min) • total liver blood flow is 100-130 ml/min per 100 g liver independent of species • 25-30% comes through HA (500 ml/min), accounts for 65% oxygen supply • HA plays important role in liver blood vessel and connective tissue perfusion and bile duct integrity • there are both common and separate channels for arterial (spotty) and portal (uniform) blood supply 5
- 6. Hepatic artery cannulation – Implications for tumor growth • Nude Rats, n = 20 • Body weight • Day 0: Huh7.5 cell implantation • Liver weight • Day 11: Serum AFP, randomize • Tumor weight • Day 12, 13: HA Surgery • AFP • Days 18, 25, 32: Serum AFP • Serum chemistry • Day 32: Necropsy • Liver function rat mouse 6
- 7. Hepatic artery cannulation – Implications for tumor growth • Hepatic Artery Cannulation procedure reduced tumor growth; • Effect of cannulation on tumor growth should be considered when designing studies using the HA dose route Serum AFP at the end of study HA cannulation canula 7
- 8. 3. Tumor vasculature: Implication for drug delivery Mucrobubble delivery system Project Objective: • Microbubbles (MB) provide an optimal, internal, minimally invasive drug-delivery vehicle. They measure 2 to 4 microns, which is smaller than the size of a red blood cell. • This dimension enables these small vehicles to easily course within the flow of the smallest blood vessels. • Once injected, Microbubbles can transport therapeutics throughout the circulatory system, with their path tracked by ultrasonic imaging. 8
- 9. Liver vasculature - Implication for drug delivery Contrast Uptake in the Liver Study goal: Assess liver take rate of contrast agent by using 3 different routs of contrast injection: 1. tail vain 2. portal vain 3. hepatic artery • Species: rats • Contrast agent: VisualSonics Micromarker bubbles • Volume of contrast injected: 50ml • Visual Sonics Ultra Sound system used in the study 9
- 10. Liver vasculature - Implication for drug delivery tail vain portal vain hepatic artery 10
- 11. ATTENTION! The entire presentation is available to registered attendees only! To view the rest of this exciting presentation and many more! Please Register for the 7th Annual Cancer Drugs Research and Development Conference at www.gtcbio.com If you are already registered, please contact GTCbio for the full version.