Zoledronate was found to reduce VEGF secretion and modulate RANKL expression in vitro in a feline OSCC cell line. Cats with OSCC had higher serum CTx levels than healthy cats. Treating cats with OSCC using zoledronate alone rapidly decreased serum VEGF and CTx levels in vivo, suggesting it may slow tumor growth and reduce cancer-induced bone destruction associated with OSCC.
Osteoblasts remotely supply lung tumors with cancer-promoting SiglecFhigh neu...Gul Muneer
Osteoblasts remotely supply lung tumors with cancer-promoting SiglecFhigh neutrophils. Lung tumors disrupt bone homeostasis and increase osteoblast activity and bone formation. Osteoblasts amplify tumor-associated SiglecFhigh neutrophils that promote tumor growth through angiogenesis, immunosuppression and other mechanisms. Serum from tumor-bearing mice increases osteoblast activity through elevated sRAGE, which stimulates neutrophil maturation. SiglecFhigh neutrophils correlate with poor survival in lung cancer patients. Therefore, lung tumors communicate with bone through factors like sRAGE to modulate osteoblasts and promote neutrophil-driven tumor progression.
Transgenic mice that overexpress the Cux-1 gene in the kidney develop glomerulosclerosis and interstitial fibrosis. The study found that Cux-1 overexpression leads to increased mesangial cell proliferation and expansion of the mesangial matrix. This results in mesangial cell hyperplasia and mesangial matrix expansion. The changes are associated with disruption of podocyte architecture and loss of kidney filtration function. Overexpression of Cux-1 is sufficient to induce early changes characteristic of mesangioproliferative glomerulonephritis.
This document describes a screen of 50,000 compounds to identify inhibitors of hepatocyte growth factor (HGF)-induced epithelial scattering. Several structurally distinct compounds were identified that had not previously been reported to have biological activity. Further analysis revealed that many of the compounds broadly inhibit cancer cell proliferation by arresting cell division in G2/M phase with minimal induction of apoptosis. This effect is consistent with microtubule-targeting agents. Biochemical assays showed that several compounds directly inhibit microtubule polymerization. Some pharmacokinetic properties of the compounds were also assessed.
immunohistochemically and in situ hybridizati.pptxMarwa972783
This document discusses immunohistochemistry and in situ hybridization detection of COX2 in salivary gland tumors. It provides background on immunohistochemistry and in situ hybridization techniques. It then describes a study that examined COX2 expression in pleomorphic adenoma and mucoepidermoid carcinoma salivary gland tumor samples using immunohistochemistry. The study found higher COX2 expression in mucoepidermoid carcinoma samples compared to pleomorphic adenoma samples.
immunohistochemically and in situ hybridizati.pptxMarwa972783
This document discusses immunohistochemistry and in situ hybridization detection of COX2 in salivary gland tumors. It provides background on immunohistochemistry and in situ hybridization techniques. It then describes a study that examined COX2 expression in pleomorphic adenoma and mucoepidermoid carcinoma salivary gland tumor samples using immunohistochemistry. The study found higher COX2 expression in mucoepidermoid carcinoma samples compared to pleomorphic adenoma samples.
This study investigated the effects of autophagy on vascular endothelial growth factor (VEGF) expression in human retinal pigment epithelial cells (RPE-19) under hypoxic conditions. RPE-19 cells were divided into control, hypoxia, and autophagy inhibitor groups. The hypoxia group showed increased autophagy marker levels and VEGF expression compared to the control group. The autophagy inhibitor group showed decreased VEGF levels compared to the hypoxia group. Additionally, inducing autophagy with rapamycin also increased VEGF expression in normal oxygen conditions. Therefore, the study concluded that autophagy promotes VEGF expression in RPE-19 cells.
Metastatic bone disease: An old dogma and a new insightMohamed Abdulla
Metastatic bone disease is a challenging condition that places a heavy burden on patients. New insights into the cellular and molecular mechanisms have led to improved treatments. Cancer cells interact with the bone microenvironment through factors like RANKL, RANK, and osteoprotegerin, inducing a "vicious cycle" of bone destruction. Emerging therapies target these interactions by inhibiting RANKL with drugs like denosumab. Radiopharmaceuticals like radium-223 also show promise by targeting areas of new bone growth in metastases. While radiation remains important for pain relief, combination therapies offer the potential for improved outcomes in metastatic bone disease.
Objective: Tongue squamous cell carcinoma (TSCC) is a prominent type of oral cancer. Despite the numerous research studies on SCC and microRNAs (miRs), the relation between TSCC and miR-135b-5p is poorly discussed. This experiment aims to find out the possible effect of miR-135b-5p on TSCC with the network of its downstream genes.
Study Design: TSCC tissues and adjacent normal tissues were harvested. Then, expression of miR-135b-5p and AT-rich interactive domain‑containing protein 1A gene (ARID1A) and the phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKT) pathway was analyzed. After the transfection of miR-135b-5p inhibitor and its negative control into TSCC cells, functional assays were employed to measure cell proliferation, apoptosis, and cycle. Next, the target relation between miR-135b-5p and ARID1A was confirmed. In addition, the fact that miR-135b-5p promoted TSCC development via mediating ARID1A was demonstrated by functional rescue experiment.
Results: miR-135b-5p was upregulated in TSCC tissues and cells, while ARID1A was suppressed (p< 0.05). Silenced miR-135b-5p discouraged TSCC cell proliferation, improved apoptosis, induced cell cycle arrest, and increased ARID1A expression while inactivating the PI3K/AKT axis (p<0.05). Furthermore, knockdown of ARID1A reversed the impacts on TSCC cell proliferation and apoptosis exerted by silencing miR-135b-5p.
Conclusion: This research supported that silenced miR-135b-5p impeded TSCC proliferation and apoptosis by promoting ARID1A and inactivating the PI3K/AKT axis, which may provide some indications for TSCC alleviation.
Keywords: apoptosis; ARID1A; ARID1A protein, human; carcinoma, squamous cell; cell line, tumor; cell proliferation; drug resistance, neoplasm; microRNA-135b-5p; microRNAs; PI3K/AKT pathway; neoplasm metastasis; neoplastic stem cells; proliferation; protein binding; tongue; tongue squamous cell carcinoma
Osteoblasts remotely supply lung tumors with cancer-promoting SiglecFhigh neu...Gul Muneer
Osteoblasts remotely supply lung tumors with cancer-promoting SiglecFhigh neutrophils. Lung tumors disrupt bone homeostasis and increase osteoblast activity and bone formation. Osteoblasts amplify tumor-associated SiglecFhigh neutrophils that promote tumor growth through angiogenesis, immunosuppression and other mechanisms. Serum from tumor-bearing mice increases osteoblast activity through elevated sRAGE, which stimulates neutrophil maturation. SiglecFhigh neutrophils correlate with poor survival in lung cancer patients. Therefore, lung tumors communicate with bone through factors like sRAGE to modulate osteoblasts and promote neutrophil-driven tumor progression.
Transgenic mice that overexpress the Cux-1 gene in the kidney develop glomerulosclerosis and interstitial fibrosis. The study found that Cux-1 overexpression leads to increased mesangial cell proliferation and expansion of the mesangial matrix. This results in mesangial cell hyperplasia and mesangial matrix expansion. The changes are associated with disruption of podocyte architecture and loss of kidney filtration function. Overexpression of Cux-1 is sufficient to induce early changes characteristic of mesangioproliferative glomerulonephritis.
This document describes a screen of 50,000 compounds to identify inhibitors of hepatocyte growth factor (HGF)-induced epithelial scattering. Several structurally distinct compounds were identified that had not previously been reported to have biological activity. Further analysis revealed that many of the compounds broadly inhibit cancer cell proliferation by arresting cell division in G2/M phase with minimal induction of apoptosis. This effect is consistent with microtubule-targeting agents. Biochemical assays showed that several compounds directly inhibit microtubule polymerization. Some pharmacokinetic properties of the compounds were also assessed.
immunohistochemically and in situ hybridizati.pptxMarwa972783
This document discusses immunohistochemistry and in situ hybridization detection of COX2 in salivary gland tumors. It provides background on immunohistochemistry and in situ hybridization techniques. It then describes a study that examined COX2 expression in pleomorphic adenoma and mucoepidermoid carcinoma salivary gland tumor samples using immunohistochemistry. The study found higher COX2 expression in mucoepidermoid carcinoma samples compared to pleomorphic adenoma samples.
immunohistochemically and in situ hybridizati.pptxMarwa972783
This document discusses immunohistochemistry and in situ hybridization detection of COX2 in salivary gland tumors. It provides background on immunohistochemistry and in situ hybridization techniques. It then describes a study that examined COX2 expression in pleomorphic adenoma and mucoepidermoid carcinoma salivary gland tumor samples using immunohistochemistry. The study found higher COX2 expression in mucoepidermoid carcinoma samples compared to pleomorphic adenoma samples.
This study investigated the effects of autophagy on vascular endothelial growth factor (VEGF) expression in human retinal pigment epithelial cells (RPE-19) under hypoxic conditions. RPE-19 cells were divided into control, hypoxia, and autophagy inhibitor groups. The hypoxia group showed increased autophagy marker levels and VEGF expression compared to the control group. The autophagy inhibitor group showed decreased VEGF levels compared to the hypoxia group. Additionally, inducing autophagy with rapamycin also increased VEGF expression in normal oxygen conditions. Therefore, the study concluded that autophagy promotes VEGF expression in RPE-19 cells.
Metastatic bone disease: An old dogma and a new insightMohamed Abdulla
Metastatic bone disease is a challenging condition that places a heavy burden on patients. New insights into the cellular and molecular mechanisms have led to improved treatments. Cancer cells interact with the bone microenvironment through factors like RANKL, RANK, and osteoprotegerin, inducing a "vicious cycle" of bone destruction. Emerging therapies target these interactions by inhibiting RANKL with drugs like denosumab. Radiopharmaceuticals like radium-223 also show promise by targeting areas of new bone growth in metastases. While radiation remains important for pain relief, combination therapies offer the potential for improved outcomes in metastatic bone disease.
Objective: Tongue squamous cell carcinoma (TSCC) is a prominent type of oral cancer. Despite the numerous research studies on SCC and microRNAs (miRs), the relation between TSCC and miR-135b-5p is poorly discussed. This experiment aims to find out the possible effect of miR-135b-5p on TSCC with the network of its downstream genes.
Study Design: TSCC tissues and adjacent normal tissues were harvested. Then, expression of miR-135b-5p and AT-rich interactive domain‑containing protein 1A gene (ARID1A) and the phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKT) pathway was analyzed. After the transfection of miR-135b-5p inhibitor and its negative control into TSCC cells, functional assays were employed to measure cell proliferation, apoptosis, and cycle. Next, the target relation between miR-135b-5p and ARID1A was confirmed. In addition, the fact that miR-135b-5p promoted TSCC development via mediating ARID1A was demonstrated by functional rescue experiment.
Results: miR-135b-5p was upregulated in TSCC tissues and cells, while ARID1A was suppressed (p< 0.05). Silenced miR-135b-5p discouraged TSCC cell proliferation, improved apoptosis, induced cell cycle arrest, and increased ARID1A expression while inactivating the PI3K/AKT axis (p<0.05). Furthermore, knockdown of ARID1A reversed the impacts on TSCC cell proliferation and apoptosis exerted by silencing miR-135b-5p.
Conclusion: This research supported that silenced miR-135b-5p impeded TSCC proliferation and apoptosis by promoting ARID1A and inactivating the PI3K/AKT axis, which may provide some indications for TSCC alleviation.
Keywords: apoptosis; ARID1A; ARID1A protein, human; carcinoma, squamous cell; cell line, tumor; cell proliferation; drug resistance, neoplasm; microRNA-135b-5p; microRNAs; PI3K/AKT pathway; neoplasm metastasis; neoplastic stem cells; proliferation; protein binding; tongue; tongue squamous cell carcinoma
The document summarizes research on targeting cancer stem cells in acute myeloid leukemia (AML). It discusses how AML stem cells, or leukemia stem cells (LSCs), drive leukemia but are overlooked by standard treatment. The research aims to understand LSC function at a molecular level to enable LSC-directed therapies for AML cure. Experiments show the transcription factor PU.1 regulates LSCs, and the drug eltrombopag may help treat thrombocytopenia in AML without activating LSCs.
The document summarizes research on targeting cancer stem cells in acute myeloid leukemia (AML). It discusses how AML stem cells, or leukemia stem cells (LSCs), differ from normal stem cells and bulk leukemia cells in their ability to self-renew and initiate leukemia. The research aims to identify molecular mechanisms driving LSC function and transforming events leading to LSC formation. Experiments show that reducing the transcription factor PU.1 induces AML by downregulating JunB expression. Additional work profiles gene expression differences between normal and AML stem/progenitor cells. The document also evaluates using the thrombopoietin receptor agonist eltrombopag to treat thrombocytopenia in AML/MDS patients,
The document summarizes research on targeting cancer stem cells in acute myeloid leukemia (AML). It discusses how AML stem cells, or leukemia stem cells (LSCs), differ from normal stem cells and bulk leukemia cells in their ability to self-renew and initiate leukemia. The research aims to identify molecular mechanisms driving LSC function and transforming events leading to LSC formation. Experiments show that reducing the transcription factor PU.1 induces AML by downregulating JunB expression. Additional work profiles gene expression differences between normal and AML stem/progenitor cells. The document also evaluates using the thrombopoietin receptor agonist eltrombopag to treat thrombocytopenia in AML/MDS patients,
The document summarizes research on targeting cancer stem cells in acute myeloid leukemia (AML). It discusses how AML stem cells (leukemia stem cells or LSCs) differ from normal stem cells in their ability to self-renew and initiate leukemia. The research aims to understand the molecular mechanisms that drive LSC function and identify transforming events involved in LSC formation and maintenance. Preclinical studies show that the transcription factor PU.1 regulates genes like JunB that are important for LSC function. The document also discusses using a small molecule drug called Eltrombopag to stimulate megakaryopoiesis in MDS/AML patients without activating LSCs, as a potential treatment for thrombocytopenia.
The flavonoid quercetin transientyly inhibits the activity of taxol and nocod...Tiensae Teshome
This study examined the effects of the flavonoid quercetin on cancer cell viability and cell cycle progression when administered alone or in combination with the microtubule-targeting drugs taxol and nocodazole. The researchers found that while quercetin induced cancer cell death in a dose-dependent manner, lower doses of quercetin protected cancer cells from the G2/M cell cycle arrest induced by taxol and nocodazole. Specifically, quercetin delayed cell cycle progression, inhibited the accumulation of cyclin B1 at the microtubule organizing center, and partially restored viability of drug-treated cells for up to 72 hours. However, long-term exposure to quercetin still suppressed cancer cell proliferation and
Proteasome inhibitors in treatment of multiple myelomaAlok Gupta
This document summarizes the development of the proteasome inhibitor bortezomib, including its mechanism of action, clinical trials, safety profile, and peripheral neuropathy issues. Key findings include:
- Bortezomib is a reversible inhibitor of the proteasome's chymotrypsin-like activity and was found to induce apoptosis in cancer cells.
- Phase I and II clinical trials demonstrated efficacy in hematological malignancies like multiple myeloma with a tolerable safety profile.
- Peripheral neuropathy is a common side effect that can often improve after stopping treatment.
- Further research aimed to improve response rates, overcome resistance, expand use to solid tumors, and address neuropathy issues.
biochem of cancer modified dialysis treatmentThomas Brinkman
This document discusses a proposed method to remove tumor-secreted exosomes from the blood to prevent cancer metastasis. Specifically, it aims to:
1. Isolate the protein on Kupffer cells that pancreatic cancer exosomes bind to via integrin proteins.
2. Create antibodies that bind to the epidermal growth factor receptor (EGFR) biomarker found on pancreatic cancer exosomes.
3. Use a modified dialysis machine with microfluidic chips containing the isolated Kupffer cell proteins and EGFR antibodies to filter pancreatic cancer exosomes from patient blood.
This method aims to prevent exosomes from forming pre-metastatic niches and promoting cancer growth and spread by
This document discusses a study that investigated how inhibiting the epidermal growth factor receptor (EGFR) signaling pathway with the anti-EGFR monoclonal antibody IMC-C225 affects nuclear factor-kappa B (NF-κB) activation and regulation of apoptosis genes in human pancreatic cancer cells. The study found that IMC-C225 treatment blocked EGFR activation in pancreatic cancer cells, leading to decreased NF-κB DNA binding activity. This downregulation of NF-κB by IMC-C225 resulted in decreased expression of the anti-apoptotic genes bcl-xl and bfl-1. Therefore, targeting the NF-κB pathway with an anti-EGFR antibody may help restore apoptosis in pancreatic cancer cells and
The document describes screening methods for new anticancer drugs. It discusses how cancer arises from genetic mutations and different cancer types. Current treatments include chemotherapy, surgery and radiation. There is a need for more selective anticancer agents due to drug resistance and side effects. Various in vitro and in vivo screening assays are described to test compounds for cytotoxicity against cancer cells and tumors in animal models. The goal is to develop more effective and safer anticancer drugs.
This study examined promoter hypermethylation of the hmlh1 gene in esophageal cancer patients from Kashmir, India. The researchers collected tumor and normal tissue samples from 50 cancer patients and 20 controls. DNA was extracted from the samples and treated to detect methylation levels. Methylation-specific PCR was performed using methylated and unmethylated primers. The frequency of hmlh1 promoter hypermethylation was 56% in cancer tissues and 15% in normal tissues, which was a statistically significant difference. The results suggest aberrant hmlh1 promoter hypermethylation may play a role in esophageal carcinogenesis in this high-risk population.
This study analyzed mutations in the von Hippel-Lindau (VHL) gene in 67 cases of renal cell carcinoma (RCC) to determine if VHL mutations could help distinguish between RCC subtypes. Single strand conformational polymorphism analysis and sequencing identified VHL mutations in RCC samples. Exon 3 mutations were found primarily in conventional (clear cell) RCC and correlated with more aggressive tumor phenotypes. Mutations were absent in papillary RCC and oncocytoma samples. VHL mutations were found to help distinguish conventional RCC from chromophobe RCC showing clear cells, serving as an adjunct to histological diagnosis of RCC subtypes.
Most Recent Studies About Stem Cell & Autoimmune Diseasemeducationdotnet
This document summarizes recent studies on the relationship between stem cell transplants and autoimmune diseases. It discusses how stem cell transplants, particularly mesenchymal stem cell transplants, have shown promise in treating several autoimmune disorders like multiple sclerosis, systemic lupus erythematosus, pemphigus vulgaris, autoimmune hepatitis, and pure red cell aplasia. The document reviews specific studies that have found stem cell transplants can reduce disease activity, induce remission, and improve organ function for these conditions. It also notes that mesenchymal stem cell transplants appear to exert anti-inflammatory and regenerative effects with few adverse side effects reported.
This study investigated the effects of high-dose ascorbic acid (ASC) alone and in combination with the drug sorafenib (SF) on liver (HepG2), brain (SKNSH), and kidney (HEK) cell lines. ASC at 5mM caused more cell death than other compounds in SKNSH and HepG2 cells. ASC combined with lower doses of SF produced greater cytotoxic effects than other combinations in SKNSH cells. While ASC and SF individually killed cancer cells in a dose-dependent manner, very high doses of ASC up to 100mM did not kill non-cancerous HEK kidney cells. The results suggest that high-dose ASC alone or with lower doses of SF
This study examined the anti-tumor effects of Jianpi Huayu decoction (JHD) on liver cancer dormancy and recurrence. A mouse model of liver cancer dormancy was used. Mice were administered different doses of JHD after tumor dormancy was disrupted. JHD increased liver cancer dormancy rates in a dose-dependent manner by inhibiting angiogenesis. It did so by decreasing levels of proteins and genes involved in angiogenesis, such as HIF-1α, VEGF, MMP-9, TIMP-1 and EMMPRIN. JHD also inhibited the proliferation of circulating endothelial cells, which are involved in tumor blood vessel formation. The results suggest JHD may enhance liver cancer dormancy by inhibiting angiogenesis
Osteoblast numbers are reduced by 55% in patients with myelodysplastic syndromes and acute myeloid leukemia. Mice models of acute leukemia also show rapid decreases in osteoblast numbers. Genetic depletion of osteoblasts in mice injected with leukemia cells leads to increased leukemia burden in bone marrow, blood, and other tissues. This suggests osteoblasts play a role in restricting leukemia progression and that compromising osteoblast function favors tumor growth. Maintaining osteoblast numbers could potentially help control leukemia by creating a less permissive microenvironment for tumor cells.
This document provides an abstract program for the 25th Annual ACVIM Forum held in Seattle, WA from June 6-9, 2007. It lists 99 oral presentations given over the four days, organized by topic area (e.g. oncology, infectious disease, cardiology, etc.). The presentations include research studies on diseases and conditions in small animals, horses, food animals, and topics related to veterinary internal medicine specialties.
This document describes a case study of a Miniature Dachshund that was diagnosed with a ventricular septal defect (VSD) and aortic regurgitation. Echocardiography revealed a defect between the ventricles and a thickened aortic valve prolapsing into the defect. Cardiac catheterization confirmed a supracristal VSD with aortic regurgitation. Despite medication, the dog's left ventricular dimensions worsened over time. The dog ultimately underwent surgery to close the VSD using cardiopulmonary bypass, which improved the condition and controlled further valve deterioration.
Este documento proporciona información sobre anestesia y analgesia en perros y gatos. Explica los fármacos utilizados para premedicación, inducción anestésica y mantenimiento anestésico, así como analgésicos intraoperatorios. Detalla esquemas de dosis comunes para diferentes tipos de procedimientos y pacientes. Los principales fármacos discutidos incluyen opiáceos, benzodiacepinas, agonistas alfa-2, ketamina e isoflurano.
Guia Practica Analgesia y Anestesia.pdfleroleroero1
El documento presenta cuatro casos de protocolos anestésicos y analgésicos para diferentes procedimientos quirúrgicos en caninos y felinos. Divide los casos en categorías según el grado de dolor esperado y propone opciones de premedicación, inducción, mantenimiento y recuperación para cada uno, destacando la importancia de adaptar los protocolos a cada paciente.
buprenorfina y medetomidina en gatos.pdfleroleroero1
This study investigated the effects of using different combinations of medetomidine and buprenorphine as preanesthetic medications in cats undergoing ovariohysterectomy. Forty cats were divided into four groups receiving different doses of medetomidine alone or in combination with buprenorphine. The results showed that cats receiving 30 μg/kg medetomidine with 20 μg/kg buprenorphine required significantly less isoflurane to maintain anesthesia compared to cats receiving medetomidine alone. Heart rate was significantly lower and oxygen saturation was slightly lower in cats receiving the highest dose of medetomidine and buprenorphine. All groups receiving medetomidine and buprenorphine experienced significantly
This document appears to be a collection of page numbers without any accompanying text. It consists of page numbers from 2 through 11 but provides no other context or information to summarize.
complicaciones en toracotmías en ghatos.pdfleroleroero1
Lateral thoracotomy is commonly used to access the thoracic cavity in dogs and cats for surgical treatment of diseases. This study reviewed 83 cases (70 dogs and 13 cats) that underwent lateral thoracotomy. The most common indication was treatment of a vascular anomaly like a patent ductus arteriosus. Overall survival to discharge was high at 87%, though cats had lower survival than dogs. Younger animals and those undergoing vascular procedures like PDA ligation had higher survival than those undergoing lung or esophageal surgery. Post-operative complications within 2 weeks were reported in 47% of cases, but long-term complications in survivors were rare.
The document summarizes research on targeting cancer stem cells in acute myeloid leukemia (AML). It discusses how AML stem cells, or leukemia stem cells (LSCs), drive leukemia but are overlooked by standard treatment. The research aims to understand LSC function at a molecular level to enable LSC-directed therapies for AML cure. Experiments show the transcription factor PU.1 regulates LSCs, and the drug eltrombopag may help treat thrombocytopenia in AML without activating LSCs.
The document summarizes research on targeting cancer stem cells in acute myeloid leukemia (AML). It discusses how AML stem cells, or leukemia stem cells (LSCs), differ from normal stem cells and bulk leukemia cells in their ability to self-renew and initiate leukemia. The research aims to identify molecular mechanisms driving LSC function and transforming events leading to LSC formation. Experiments show that reducing the transcription factor PU.1 induces AML by downregulating JunB expression. Additional work profiles gene expression differences between normal and AML stem/progenitor cells. The document also evaluates using the thrombopoietin receptor agonist eltrombopag to treat thrombocytopenia in AML/MDS patients,
The document summarizes research on targeting cancer stem cells in acute myeloid leukemia (AML). It discusses how AML stem cells, or leukemia stem cells (LSCs), differ from normal stem cells and bulk leukemia cells in their ability to self-renew and initiate leukemia. The research aims to identify molecular mechanisms driving LSC function and transforming events leading to LSC formation. Experiments show that reducing the transcription factor PU.1 induces AML by downregulating JunB expression. Additional work profiles gene expression differences between normal and AML stem/progenitor cells. The document also evaluates using the thrombopoietin receptor agonist eltrombopag to treat thrombocytopenia in AML/MDS patients,
The document summarizes research on targeting cancer stem cells in acute myeloid leukemia (AML). It discusses how AML stem cells (leukemia stem cells or LSCs) differ from normal stem cells in their ability to self-renew and initiate leukemia. The research aims to understand the molecular mechanisms that drive LSC function and identify transforming events involved in LSC formation and maintenance. Preclinical studies show that the transcription factor PU.1 regulates genes like JunB that are important for LSC function. The document also discusses using a small molecule drug called Eltrombopag to stimulate megakaryopoiesis in MDS/AML patients without activating LSCs, as a potential treatment for thrombocytopenia.
The flavonoid quercetin transientyly inhibits the activity of taxol and nocod...Tiensae Teshome
This study examined the effects of the flavonoid quercetin on cancer cell viability and cell cycle progression when administered alone or in combination with the microtubule-targeting drugs taxol and nocodazole. The researchers found that while quercetin induced cancer cell death in a dose-dependent manner, lower doses of quercetin protected cancer cells from the G2/M cell cycle arrest induced by taxol and nocodazole. Specifically, quercetin delayed cell cycle progression, inhibited the accumulation of cyclin B1 at the microtubule organizing center, and partially restored viability of drug-treated cells for up to 72 hours. However, long-term exposure to quercetin still suppressed cancer cell proliferation and
Proteasome inhibitors in treatment of multiple myelomaAlok Gupta
This document summarizes the development of the proteasome inhibitor bortezomib, including its mechanism of action, clinical trials, safety profile, and peripheral neuropathy issues. Key findings include:
- Bortezomib is a reversible inhibitor of the proteasome's chymotrypsin-like activity and was found to induce apoptosis in cancer cells.
- Phase I and II clinical trials demonstrated efficacy in hematological malignancies like multiple myeloma with a tolerable safety profile.
- Peripheral neuropathy is a common side effect that can often improve after stopping treatment.
- Further research aimed to improve response rates, overcome resistance, expand use to solid tumors, and address neuropathy issues.
biochem of cancer modified dialysis treatmentThomas Brinkman
This document discusses a proposed method to remove tumor-secreted exosomes from the blood to prevent cancer metastasis. Specifically, it aims to:
1. Isolate the protein on Kupffer cells that pancreatic cancer exosomes bind to via integrin proteins.
2. Create antibodies that bind to the epidermal growth factor receptor (EGFR) biomarker found on pancreatic cancer exosomes.
3. Use a modified dialysis machine with microfluidic chips containing the isolated Kupffer cell proteins and EGFR antibodies to filter pancreatic cancer exosomes from patient blood.
This method aims to prevent exosomes from forming pre-metastatic niches and promoting cancer growth and spread by
This document discusses a study that investigated how inhibiting the epidermal growth factor receptor (EGFR) signaling pathway with the anti-EGFR monoclonal antibody IMC-C225 affects nuclear factor-kappa B (NF-κB) activation and regulation of apoptosis genes in human pancreatic cancer cells. The study found that IMC-C225 treatment blocked EGFR activation in pancreatic cancer cells, leading to decreased NF-κB DNA binding activity. This downregulation of NF-κB by IMC-C225 resulted in decreased expression of the anti-apoptotic genes bcl-xl and bfl-1. Therefore, targeting the NF-κB pathway with an anti-EGFR antibody may help restore apoptosis in pancreatic cancer cells and
The document describes screening methods for new anticancer drugs. It discusses how cancer arises from genetic mutations and different cancer types. Current treatments include chemotherapy, surgery and radiation. There is a need for more selective anticancer agents due to drug resistance and side effects. Various in vitro and in vivo screening assays are described to test compounds for cytotoxicity against cancer cells and tumors in animal models. The goal is to develop more effective and safer anticancer drugs.
This study examined promoter hypermethylation of the hmlh1 gene in esophageal cancer patients from Kashmir, India. The researchers collected tumor and normal tissue samples from 50 cancer patients and 20 controls. DNA was extracted from the samples and treated to detect methylation levels. Methylation-specific PCR was performed using methylated and unmethylated primers. The frequency of hmlh1 promoter hypermethylation was 56% in cancer tissues and 15% in normal tissues, which was a statistically significant difference. The results suggest aberrant hmlh1 promoter hypermethylation may play a role in esophageal carcinogenesis in this high-risk population.
This study analyzed mutations in the von Hippel-Lindau (VHL) gene in 67 cases of renal cell carcinoma (RCC) to determine if VHL mutations could help distinguish between RCC subtypes. Single strand conformational polymorphism analysis and sequencing identified VHL mutations in RCC samples. Exon 3 mutations were found primarily in conventional (clear cell) RCC and correlated with more aggressive tumor phenotypes. Mutations were absent in papillary RCC and oncocytoma samples. VHL mutations were found to help distinguish conventional RCC from chromophobe RCC showing clear cells, serving as an adjunct to histological diagnosis of RCC subtypes.
Most Recent Studies About Stem Cell & Autoimmune Diseasemeducationdotnet
This document summarizes recent studies on the relationship between stem cell transplants and autoimmune diseases. It discusses how stem cell transplants, particularly mesenchymal stem cell transplants, have shown promise in treating several autoimmune disorders like multiple sclerosis, systemic lupus erythematosus, pemphigus vulgaris, autoimmune hepatitis, and pure red cell aplasia. The document reviews specific studies that have found stem cell transplants can reduce disease activity, induce remission, and improve organ function for these conditions. It also notes that mesenchymal stem cell transplants appear to exert anti-inflammatory and regenerative effects with few adverse side effects reported.
This study investigated the effects of high-dose ascorbic acid (ASC) alone and in combination with the drug sorafenib (SF) on liver (HepG2), brain (SKNSH), and kidney (HEK) cell lines. ASC at 5mM caused more cell death than other compounds in SKNSH and HepG2 cells. ASC combined with lower doses of SF produced greater cytotoxic effects than other combinations in SKNSH cells. While ASC and SF individually killed cancer cells in a dose-dependent manner, very high doses of ASC up to 100mM did not kill non-cancerous HEK kidney cells. The results suggest that high-dose ASC alone or with lower doses of SF
This study examined the anti-tumor effects of Jianpi Huayu decoction (JHD) on liver cancer dormancy and recurrence. A mouse model of liver cancer dormancy was used. Mice were administered different doses of JHD after tumor dormancy was disrupted. JHD increased liver cancer dormancy rates in a dose-dependent manner by inhibiting angiogenesis. It did so by decreasing levels of proteins and genes involved in angiogenesis, such as HIF-1α, VEGF, MMP-9, TIMP-1 and EMMPRIN. JHD also inhibited the proliferation of circulating endothelial cells, which are involved in tumor blood vessel formation. The results suggest JHD may enhance liver cancer dormancy by inhibiting angiogenesis
Osteoblast numbers are reduced by 55% in patients with myelodysplastic syndromes and acute myeloid leukemia. Mice models of acute leukemia also show rapid decreases in osteoblast numbers. Genetic depletion of osteoblasts in mice injected with leukemia cells leads to increased leukemia burden in bone marrow, blood, and other tissues. This suggests osteoblasts play a role in restricting leukemia progression and that compromising osteoblast function favors tumor growth. Maintaining osteoblast numbers could potentially help control leukemia by creating a less permissive microenvironment for tumor cells.
Similar to dUCTO CERRADO POR MINI INVASIVA.pdf (15)
This document provides an abstract program for the 25th Annual ACVIM Forum held in Seattle, WA from June 6-9, 2007. It lists 99 oral presentations given over the four days, organized by topic area (e.g. oncology, infectious disease, cardiology, etc.). The presentations include research studies on diseases and conditions in small animals, horses, food animals, and topics related to veterinary internal medicine specialties.
This document describes a case study of a Miniature Dachshund that was diagnosed with a ventricular septal defect (VSD) and aortic regurgitation. Echocardiography revealed a defect between the ventricles and a thickened aortic valve prolapsing into the defect. Cardiac catheterization confirmed a supracristal VSD with aortic regurgitation. Despite medication, the dog's left ventricular dimensions worsened over time. The dog ultimately underwent surgery to close the VSD using cardiopulmonary bypass, which improved the condition and controlled further valve deterioration.
Este documento proporciona información sobre anestesia y analgesia en perros y gatos. Explica los fármacos utilizados para premedicación, inducción anestésica y mantenimiento anestésico, así como analgésicos intraoperatorios. Detalla esquemas de dosis comunes para diferentes tipos de procedimientos y pacientes. Los principales fármacos discutidos incluyen opiáceos, benzodiacepinas, agonistas alfa-2, ketamina e isoflurano.
Guia Practica Analgesia y Anestesia.pdfleroleroero1
El documento presenta cuatro casos de protocolos anestésicos y analgésicos para diferentes procedimientos quirúrgicos en caninos y felinos. Divide los casos en categorías según el grado de dolor esperado y propone opciones de premedicación, inducción, mantenimiento y recuperación para cada uno, destacando la importancia de adaptar los protocolos a cada paciente.
buprenorfina y medetomidina en gatos.pdfleroleroero1
This study investigated the effects of using different combinations of medetomidine and buprenorphine as preanesthetic medications in cats undergoing ovariohysterectomy. Forty cats were divided into four groups receiving different doses of medetomidine alone or in combination with buprenorphine. The results showed that cats receiving 30 μg/kg medetomidine with 20 μg/kg buprenorphine required significantly less isoflurane to maintain anesthesia compared to cats receiving medetomidine alone. Heart rate was significantly lower and oxygen saturation was slightly lower in cats receiving the highest dose of medetomidine and buprenorphine. All groups receiving medetomidine and buprenorphine experienced significantly
This document appears to be a collection of page numbers without any accompanying text. It consists of page numbers from 2 through 11 but provides no other context or information to summarize.
complicaciones en toracotmías en ghatos.pdfleroleroero1
Lateral thoracotomy is commonly used to access the thoracic cavity in dogs and cats for surgical treatment of diseases. This study reviewed 83 cases (70 dogs and 13 cats) that underwent lateral thoracotomy. The most common indication was treatment of a vascular anomaly like a patent ductus arteriosus. Overall survival to discharge was high at 87%, though cats had lower survival than dogs. Younger animals and those undergoing vascular procedures like PDA ligation had higher survival than those undergoing lung or esophageal surgery. Post-operative complications within 2 weeks were reported in 47% of cases, but long-term complications in survivors were rare.
1) The document describes a novel axial pattern flap for nasal and facial reconstruction in dogs. The flap is based on the commissure of the lip and receives blood supply from the angularis oris artery and other arteries.
2) Cadaver studies and dye infusion showed the flap has a reliable blood supply from three direct cutaneous arteries. The flap survived with good results in four clinical cases to reconstruct large facial or nasal defects.
3) The flap provides sufficient skin to reconstruct large defects involving the nose or face. It has a reliable blood supply and versatile design that allows it to be used for various reconstruction needs in dogs.
Laboratorios Richmond División Veterinaria es una empresa argentina dedicada al desarrollo y producción de medicamentos y equipamiento veterinario. Cuenta con instalaciones de investigación, desarrollo y producción que cumplen con los estándares GMP. Exporta sus productos a varios países de América Latina, África y Asia, ofreciendo tratamientos para una variedad de especies animales.
This study evaluated the effect of preoperative intrathecal administration of a low dose of morphine on intraoperative fentanyl requirements in dogs undergoing spinal surgery. Eighteen dogs undergoing cervical or thoracolumbar laminectomy were randomly assigned to receive intrathecal morphine (MG group) or no treatment (CG group). The MG group had significantly lower hourly fentanyl consumption and lower predicted plasma fentanyl concentrations compared to the CG group. This suggests that a low dose of preoperative intrathecal morphine has a sparing effect on intraoperative fentanyl requirements in dogs undergoing spinal surgery. No adverse effects were observed from the intrathecal morphine administration.
This study evaluated the effects of postoperative ketamine administration on pain control and feeding behavior in dogs undergoing mastectomy. Twenty-seven dogs undergoing mastectomy were randomly assigned to receive either placebo, low-dose ketamine, or high-dose ketamine intravenously at the end of surgery and as a 6-hour infusion. Pain levels, opioid requirements, sedation, and food intake were evaluated and compared between groups. The high-dose ketamine group showed significantly improved feeding behavior 20 hours after surgery compared to the low-dose and placebo groups, but opioid requirements did not differ significantly between groups.
This study evaluated 59 cats that underwent perineal urethrostomy surgery for feline lower urinary tract disease (FLUTD) at a university veterinary clinic. Early complications within 4 weeks of surgery occurred in 25.4% of cats, most commonly urethral stricture formation. Late complications after at least 4 months included recurring urinary tract infections in 28.2% of cats. Despite frequent complications, 32.2% of cats had no long-term issues, though recurring FLUTD symptoms still occurred in 23% of cats. Overall, the surgery provided a good quality of life for most cats, according to their owners.
This study evaluated the effects of acepromazine (a sedative) on cardiovascular changes induced by dopamine in anesthetized dogs. The researchers found that:
1) Acepromazine prevented the normal return of systemic vascular resistance to baseline levels during higher dopamine doses and reduced the magnitude of arterial pressure increases from dopamine.
2) However, acepromazine did not modify dopamine's ability to increase cardiac index and oxygen delivery, which are beneficial effects.
3) Previous acepromazine administration reduces dopamine's efficacy as a vasopressor agent under isoflurane anesthesia in dogs, but does not alter its other beneficial hemodynamic effects.
recuperación en hipotermia anestesia.pdfleroleroero1
Lower core body temperatures were associated with longer recovery times from general anesthesia in dogs undergoing routine sterilization surgery. Oesophageal temperatures at the end of surgery averaged 36.8°C, with lower temperatures correlated with significantly slower recoveries. Premedication with acepromazine and morphine also significantly increased recovery times compared to dogs that were not premedicated. The choice of induction or maintenance anesthetic agent did not affect recovery time. Hypothermia during general anesthesia can slow recovery through multiple mechanisms, such as decreasing anesthetic requirements and impairing drug metabolism.
This document summarizes a study on the survival characteristics and prognostic variables of dogs with myxomatous mitral valve disease (MMVD), the most common heart disease in dogs. The study included 558 dogs of varying breeds and severity of MMVD. Clinical exams, echocardiograms, and follow-up phone interviews with owners were conducted to evaluate survival times and prognostic factors. Variables found to be associated with reduced survival in univariate analysis included older age, syncope, increased heart rate and dyspnea, higher ISACHC heart failure class, diuretic use, increased end-systolic volume, enlarged left atrium, and higher transmitral flow velocities. Multivariate analysis identified syncope, enlarged left atrium
Este documento presenta información sobre fisiología cardiovascular, respiratoria y del sistema nervioso central. En tres oraciones: 1) Detalla parámetros hemodinámicos como presiones arteriales, índice cardíaco y resistencias vasculares. 2) Explica conceptos como contenido de oxígeno arterial y venoso, transporte de oxígeno y ecuaciones relacionadas a la ventilación. 3) Describe características del flujo sanguíneo cerebral y su regulación, así como parámetros del líquido cefalorraquídeo.
This study evaluated the effects of ephedrine and dopamine on cardiovascular parameters in anesthetized dogs experiencing hypotension. Twelve healthy dogs undergoing orthopedic surgery were randomly assigned to treatment with either ephedrine or dopamine if their mean arterial pressure dropped below 60 mmHg under isoflurane anesthesia. Both drugs improved cardiac output and oxygen delivery, but ephedrine only transiently increased blood pressure while dopamine maintained blood pressure and total peripheral resistance at a higher infusion rate. The study concluded that while both drugs were effective at improving hemodynamics, dopamine provided more sustained blood pressure support.
This document provides guidelines for the recognition, assessment, and treatment of pain in cats and dogs. It discusses the physiology and pathophysiology of pain, as well as methods for assessing acute and chronic pain. Guidelines are provided for managing pain associated with various procedures and conditions through the use of analgesics like opioids, NSAIDs, alpha2 agonists, and local anesthetics. Non-pharmacological approaches like rehabilitation, nutrition, and massage are also addressed. The document aims to help veterinarians effectively recognize and minimize pain in small animal patients.
Este documento describe las bases neuroanatómicas del dolor, incluyendo las vías periféricas y centrales de la transmisión del impulso nociceptivo. También discute el reconocimiento y tratamiento farmacológico del dolor en pequeños animales.
This study compared sevoflurane and isoflurane for maintaining anesthesia in 108 dogs undergoing surgical or diagnostic procedures. Dogs were randomly assigned to receive either sevoflurane (group S) or isoflurane (group I). Both groups had similar heart rates, respiratory rates, blood pressures, temperatures, and times to recovery. However, end-tidal carbon dioxide levels were higher in group S from 30-60 minutes after induction. Sevoflurane required higher vaporizer settings throughout but no adverse events occurred. The study concluded that sevoflurane was a suitable volatile anesthetic for maintaining routine clinical anesthesia in dogs.
Pictorial and detailed description of patellar instability with sign and symptoms and how to diagnose , what investigations you should go with and how to approach with treatment options . I have presented this slide in my 2nd year junior residency in orthopedics at LLRM medical college Meerut and got good reviews for it
After getting it read you will definitely understand the topic.
5-hydroxytryptamine or 5-HT or Serotonin is a neurotransmitter that serves a range of roles in the human body. It is sometimes referred to as the happy chemical since it promotes overall well-being and happiness.
It is mostly found in the brain, intestines, and blood platelets.
5-HT is utilised to transport messages between nerve cells, is known to be involved in smooth muscle contraction, and adds to overall well-being and pleasure, among other benefits. 5-HT regulates the body's sleep-wake cycles and internal clock by acting as a precursor to melatonin.
It is hypothesised to regulate hunger, emotions, motor, cognitive, and autonomic processes.
The biomechanics of running involves the study of the mechanical principles underlying running movements. It includes the analysis of the running gait cycle, which consists of the stance phase (foot contact to push-off) and the swing phase (foot lift-off to next contact). Key aspects include kinematics (joint angles and movements, stride length and frequency) and kinetics (forces involved in running, including ground reaction and muscle forces). Understanding these factors helps in improving running performance, optimizing technique, and preventing injuries.
The Children are very vulnerable to get affected with respiratory disease.
In our country, the respiratory Disease conditions are consider as major cause for mortality and Morbidity in Child.
This presentation gives information on the pharmacology of Prostaglandins, Thromboxanes and Leukotrienes i.e. Eicosanoids. Eicosanoids are signaling molecules derived from polyunsaturated fatty acids like arachidonic acid. They are involved in complex control over inflammation, immunity, and the central nervous system. Eicosanoids are synthesized through the enzymatic oxidation of fatty acids by cyclooxygenase and lipoxygenase enzymes. They have short half-lives and act locally through autocrine and paracrine signaling.
- Video recording of this lecture in English language: https://youtu.be/RvdYsTzgQq8
- Video recording of this lecture in Arabic language: https://youtu.be/ECILGWtgZko
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Giloy in Ayurveda - Classical Categorization and SynonymsPlanet Ayurveda
Giloy, also known as Guduchi or Amrita in classical Ayurvedic texts, is a revered herb renowned for its myriad health benefits. It is categorized as a Rasayana, meaning it has rejuvenating properties that enhance vitality and longevity. Giloy is celebrated for its ability to boost the immune system, detoxify the body, and promote overall wellness. Its anti-inflammatory, antipyretic, and antioxidant properties make it a staple in managing conditions like fever, diabetes, and stress. The versatility and efficacy of Giloy in supporting health naturally highlight its importance in Ayurveda. At Planet Ayurveda, we provide a comprehensive range of health services and 100% herbal supplements that harness the power of natural ingredients like Giloy. Our products are globally available and affordable, ensuring that everyone can benefit from the ancient wisdom of Ayurveda. If you or your loved ones are dealing with health issues, contact Planet Ayurveda at 01725214040 to book an online video consultation with our professional doctors. Let us help you achieve optimal health and wellness naturally.
Dr. Tan's Balance Method.pdf (From Academy of Oriental Medicine at Austin)GeorgeKieling1
Home
Organization
Academy of Oriental Medicine at Austin
Academy of Oriental Medicine at Austin
Academy of Oriental Medicine at Austin
About AOMA: The Academy of Oriental Medicine at Austin offers a masters-level graduate program in acupuncture and Oriental medicine, preparing its students for careers as skilled, professional practitioners. AOMA is known for its internationally recognized faculty, award-winning student clinical internship program, and herbal medicine program. Since its founding in 1993, AOMA has grown rapidly in size and reputation, drawing students from around the nation and faculty from around the world. AOMA also conducts more than 20,000 patient visits annually in its student and professional clinics. AOMA collaborates with Western healthcare institutions including the Seton Family of Hospitals, and gives back to the community through partnerships with nonprofit organizations and by providing free and reduced price treatments to people who cannot afford them. The Academy of Oriental Medicine at Austin is located at 2700 West Anderson Lane. AOMA also serves patients and retail customers at its south Austin location, 4701 West Gate Blvd. For more information see www.aoma.edu or call 512-492-303434.
Breast cancer: Post menopausal endocrine therapyDr. Sumit KUMAR
Breast cancer in postmenopausal women with hormone receptor-positive (HR+) status is a common and complex condition that necessitates a multifaceted approach to management. HR+ breast cancer means that the cancer cells grow in response to hormones such as estrogen and progesterone. This subtype is prevalent among postmenopausal women and typically exhibits a more indolent course compared to other forms of breast cancer, which allows for a variety of treatment options.
Diagnosis and Staging
The diagnosis of HR+ breast cancer begins with clinical evaluation, imaging, and biopsy. Imaging modalities such as mammography, ultrasound, and MRI help in assessing the extent of the disease. Histopathological examination and immunohistochemical staining of the biopsy sample confirm the diagnosis and hormone receptor status by identifying the presence of estrogen receptors (ER) and progesterone receptors (PR) on the tumor cells.
Staging involves determining the size of the tumor (T), the involvement of regional lymph nodes (N), and the presence of distant metastasis (M). The American Joint Committee on Cancer (AJCC) staging system is commonly used. Accurate staging is critical as it guides treatment decisions.
Treatment Options
Endocrine Therapy
Endocrine therapy is the cornerstone of treatment for HR+ breast cancer in postmenopausal women. The primary goal is to reduce the levels of estrogen or block its effects on cancer cells. Commonly used agents include:
Selective Estrogen Receptor Modulators (SERMs): Tamoxifen is a SERM that binds to estrogen receptors, blocking estrogen from stimulating breast cancer cells. It is effective but may have side effects such as increased risk of endometrial cancer and thromboembolic events.
Aromatase Inhibitors (AIs): These drugs, including anastrozole, letrozole, and exemestane, lower estrogen levels by inhibiting the aromatase enzyme, which converts androgens to estrogen in peripheral tissues. AIs are generally preferred in postmenopausal women due to their efficacy and safety profile compared to tamoxifen.
Selective Estrogen Receptor Downregulators (SERDs): Fulvestrant is a SERD that degrades estrogen receptors and is used in cases where resistance to other endocrine therapies develops.
Combination Therapies
Combining endocrine therapy with other treatments enhances efficacy. Examples include:
Endocrine Therapy with CDK4/6 Inhibitors: Palbociclib, ribociclib, and abemaciclib are CDK4/6 inhibitors that, when combined with endocrine therapy, significantly improve progression-free survival in advanced HR+ breast cancer.
Endocrine Therapy with mTOR Inhibitors: Everolimus, an mTOR inhibitor, can be added to endocrine therapy for patients who have developed resistance to aromatase inhibitors.
Chemotherapy
Chemotherapy is generally reserved for patients with high-risk features, such as large tumor size, high-grade histology, or extensive lymph node involvement. Regimens often include anthracyclines and taxanes.
June 2024 Oncology Cartoons By Dr Kanhu Charan Patro
dUCTO CERRADO POR MINI INVASIVA.pdf
1. In Vivo and In Vitro Efficacy of Zoledronate for Treating Oral
Squamous Cell Carcinoma in Cats
J.M. Wypij, T.M. Fan, R.L. Fredrickson, A.M. Barger, L.P. de Lorimier, and S.C. Charney
Background: Feline oral squamous cell carcinoma (OSCC) may cause painful bone destruction. Given the local invasiveness
and rapid clinical progression of OSCC, conventional therapies are often palliative. In human cancer patients, zoledronate
exerts anticancer effects by inhibiting tumor-induced angiogenesis and malignant osteolysis.
Hypothesis: Zoledronate will exert in vitro and in vivo anti-angiogenic and antiresorptive effects in feline OSCC.
Animals: Eight cats with OSCC were prospectively treated with zoledronate and conventional treatment modalities.
Methods: In vitro, zoledronate’s effects in modulating soluble vascular endothelial growth factor (VEGF) secretion and
receptor activator of nuclear factor KB (NF-kB) ligand (RANKL) expression were investigated in a feline OSCC cell line
(SCCF1). In vivo, basal serum C-telopeptide (CTx) concentrations were compared among normal and OSCC-bearing cats, and
the biologic effects of zoledronate administration in cats with naturally occurring OSCC were quantified by serially assessing
circulating serum VEGF and CTx concentrations.
Results: In vitro, zoledronate concentrations greater than 3 mM reduce soluble VEGF secretion in the SCCF1 cell line. The
expression of RANKL in the SCCF1 cell line was also modulated by zoledronate, with low concentrations (3 mM) decreasing
but higher concentrations (30 mM) increasing RANKL expression in comparison with untreated cells. In vivo, cats with bone-
invasive OSCC had greater serum CTx concentrations in comparison with geriatric, healthy controls. Treatment with zoled-
ronate rapidly decreased circulating serum VEGF and CTx concentrations in cats with spontaneously occurring OSCC.
Conclusions and Clinical Importance: Zoledronate exerts in vitro and in vivo effects that may favor the slowing of tumor
growth and pathologic bone turnover associated with OSCC.
Key words: Aminobisphosphonate; Cancer; Focal malignant osteolysis; Serum C-telopeptide; Soluble vascular endothelial
growth factor.
Oral squamous cell carcinoma (OSCC) accounts for
approximately 75% of malignancies involving the
oral cavity of cats. The tumor is invasive, resulting in
osteolysis and cancer-associated pain.1–3
Given the local
invasiveness of OSCC and the morbidity associated with
radical oral surgery in cats,4,5
curative intent resection is
usually not feasible. Treatment options for inoperable
OSCC remain palliative and include systemic chemother-
apy, coarse-fractionated radiation therapy, or a
combination of each. Responses to systemic chemother-
apy or palliative radiation therapy alone have been
disappointing, although radiation therapy combined
with either radiosensitizing agents or hyperthermia may
be more effective.6–12
The long-term prognosis for cats
with OSCC is poor, and for cats with incurable disease,
novel adjuvant therapies that slow down tumor growth
(anti-angiogenic therapies) or minimize cancer-induced
pain (antiresorptive therapies) warrant additional inves-
tigation.
Angiogenesis is considered a fundamental hallmark of
cancer,13
and is necessary for continued primary tumor
growth and successful distant metastases.14
Principally
regulated by vascular endothelial growth factor
(VEGF),15
angiogenesis is characterized by endothelial
cell proliferation, migration, and lumen formation.16
Given that sustained angiogenesis is a prerequisite for
tumor growth, therapeutic strategies that reduce or block
the effects of tumor-associated VEGF are currently being
investigated for the treatment of various cancers.17
Similar to angiogenesis, tissue invasion is another hall-
mark of malignantly transformed cells.13
Focal osteolysis
is a prerequisite for cancer cells to successful invade min-
eralized bone. Tumor-induced bone resorption is
mediated directly by cell surface ligands or indirectly
through the release of soluble factors that promote
osteoclast activity.18
Cancer cells that directly express
surface receptor activator of nuclear factor KB (NF-kB)
ligand (RANKL) are capable of subverting homeostatic
bone turnover mechanisms to cause pathologic bone re-
sorption.19,20
Because malignant osteolysis dramatically
reduces quality-of-life scores in humans with skeletal
neoplasms, antiresorptive therapies are being investigat-
ed for the management of tumor types that preferentially
metastasize to or invade bone.21
Zoledronate, a potent aminobisphosphonate, exerts
several in vitro antineoplastic effects, including the im-
pairment of neoplastic neovascularization, tumor cell
invasion, and migration.22–24
Zoledronate administra-
tion decreases tumor angiogenesis and inhibits
malignant osteolysis in rodent tumor models,22,25–27
and
treatment decreases the number of skeletal-related
events, improves pain scores, decreases serum markers
of bone lysis, and decreases serum VEGF concentrations
From the Comparative Oncology Research Laboratory, Depart-
ment of Veterinary Clinical Medicine (Wypij, Fan, de Lorimier,
Charney) and the Department of Pathology, University of Illinois at
Urbana-Champaign, IL 61802 (Fredrickson, Barger). Findings of
this study were presented in part at the 24th Annual Veterinary Can-
cer Society Conference, Kansas City, MO, 2004; the 25th Annual
Veterinary Cancer Society Conference, Huntington Beach, CA, 2005;
and the 26th Annual Veterinary Cancer Society Conference, Pine
Mountain, GA, 2006.
This study was conducted at the Comparative Oncology Research
Laboratory.
Corresponding author:Timothy M. Fan, DVM, PhD, Department
of Veterinary Clinical Medicine, University of Illinois at Urbana-
Champaign, 1008 West Hazelwood Drive, Urbana, IL 61802; e-mail:
t-fan@uiuc.edu.
Submitted February 24, 2007; Revised May 7, July 7, 2007;
Accepted August 9, 2007.
Copyright r 2008 by the American College of Veterinary Internal
Medicine
10.1111/j.1939-1676.2007.0010.x
J Vet Intern Med 2008;22:158–163
2. in people with metastatic bone tumors.28–31
Zoledronate
is first-line treatment for people with cancers associated
with neovascularization and malignant bone destruction.
Being a standard adjunctive treatment for malignant
osteolytic diseases in human cancer patients, zoledronate
might provide therapeutic benefit for managing cats with
bone-invasive OSCC. Therefore, the first purpose of this
study was to investigate the in vitro effects of zoledronate
on VEGF secretion and surface RANKL expression in
an immortalized feline OSCC cell line (SCCF1). The sec-
ond objective of this study was to characterize serum
CTx concentrations, a bone resorption marker, in
healthy, geriatric cats and in cats with bone-invasive
OSCC. The last purpose of this study was to determine
whether zoledronate administration in cats with bone-
invasive OSCC exerted any potential anticancer effects,
assessed by changes in circulating serum VEGF and
serum CTx concentrations.
Materials and Methods
Cell Lines
A feline OSCC cell line SCCF1 (provided by Dr Thomas J.
Rosol, Ohio State University) was evaluated for soluble VEGF se-
cretion and RANKL expression. The SCCF1 cell line was grown in
Williams E mediaa
supplemented with 2 mM L-glutamine,b
0.05 mg/
mL gentamicin,c
10 ng/mL epidermal growth factor,d
0.01 nM chol-
era toxin,e
and 10% fetal bovine serum (FBS). Cell cultures were
maintained in subconfluent monolayers at 37 1C in 5% CO2 and
passaged twice weekly.
Reagents and Antibodies
Zoledronic phosphonic acid monohydratef
was obtained from
Novartis Pharmaceuticals Ltd. Stock solutions (1 mg/mL) were pre-
pared in sterile phosphate-buffered saline (PBS), aliquoted, and
frozen at 20 1C until use. The rabbit polyclonal anti human
RANKL antibodyg
used for flow cytometry has previously been
demonstrated to cross-react with canine and feline neoplastic cells.32
A corresponding rabbit immunoglobulin G (IgG1)h
was used as an
isotype control for flow cytometric analysis. The secondary anti-
body used for flow cytometry was a goat anti rabbit IgG:FITC
conjugate.i
Soluble VEGF Secretion in the SCCF1 Cell Line
SCCF1 cells were plated at a density of 2 104
cells per 250 mL of
complete medium in a 96-well microtiter plate and incubated at
37 1C and 5% CO2. After allowing cells to adhere for 24 hours, the
medium was decanted and replaced with fresh medium containing
various concentrations of zoledronate (0, 1, 3, 10, and 30 mM), and
cells were allowed to grow for an additional 48 hours. Cell culture
supernatants (in quadruplicate) were harvested and soluble VEGF
was determined with a commercially available immunoassayj
previ-
ously demonstrated to be cross-reactive with feline VEGF.33
Differences in soluble VEGF secreted by SCCF1 after zoledronate
exposure were normalized, based on differences in cell proliferation
through the use of a nonradioactive colorimetric proliferation
assayk
in which optical density linearly correlates with viable cell
numbers. Specifically, normalized VEGF concentrations were based
on the average of quadruplicate samples for each experimental
group expressed as the following ratio:
Normalized VEGF ¼ ½Calculated VEGFðpg=mLÞ=optical density:
RANKL Expression in the SCCF1 Cell Line
SCCF1 cells were plated at a density of 5105
cells per T25 tissue
culture flask in complete medium and incubated at 37 1C and 5%
CO2. After allowing the cells to adhere for 24 hours, medium was
decanted and replaced with fresh medium containing various con-
centrations of zoledronate (0, 3, and 30 mM), and cells were allowed
to grow for an additional 48 hours. Adherent SCCF1 cells were col-
lected and washed after trypsinization, and relative RANKL
protein expression by SCCF1 cells was determined by flow cytome-
try by a technique described previously.32
Samples were analyzed
with a Coulter flow cytometer (Beckman Coulter, Fullerton, CA),
and cells were gated based on their forward and side scatter prop-
erties and FITC fluorescence. Relative RANKL protein expressions
were reported as mean fluorescent intensity (MFI).
Basal Serum C-Telopeptide (CTx) Determinations in
Healthy, Geriatric, and OSCC-Bearing Cats
Venous blood samples were collected via jugular venipuncture
from 10 healthy, geriatric cats and 8 cats with histologically con-
firmed, bone-invasive OSCC for the assessment of basal serum CTx
concentrations. The 10 cats used as healthy, geriatric controls were
owned by house officers, and were considered to be in good health
based on history, physical examination, and serum biochemistry
profile. Whole blood samples were centrifuged for 10 minutes at
450 g, and serum was separated and stored at 20 1C in 2 -mL
polypropylene cryovials until analysis. Serum CTx concentrations
were measured by a commercially available immunoassay,l
previ-
ously validated for use in the cat.34
Zoledronate Treatment Study Population
All cats had a diagnosis of OSCC confirmed by histopathology
and palpable, radiographic, or computed tomographic evidence of
bone involvement. All pet owners were informed of available treat-
ment options, and cats were treated in accordance with the animal
care guidelines of the University of Illinois Institutional Animal
Care and Use Committee. All cats were considered eligible to re-
ceive zoledronate by intravenous infusion regardless of prior
treatment or concurrent disease status. As such, the extent of clin-
ical staging was variable. All cats had serum biochemistry profiles
before and after receiving zoledronate. For cats receiving more than
a single dose, all had complete physical examinations and serum
biochemistry profiles before each successive zoledronate treatment
cycle. Zoledronate was administered at 0.2 mg/kg diluted into
25 mL of 0.9% saline, and administered as a 15-minute constant
rate intravenous infusion every 28 days, a regimen derived and
modified from a previous study conducted in healthy dogs.35
In or-
der to assess the immediate biologic effect of single-agent
zoledronate, no other therapies were instituted for the 24-hour pe-
riod after the first zoledronate administration.
Serum VEGF and CTx in Zoledronate-Treated
OSCC-Bearing Cats
Venous blood samples were collected via jugular venipuncture
for the assessment of serum soluble VEGF and CTx concentrations.
To ensure that changes in serum VEGF and CTx concentrations
were indeed an effect of zoledronate and not other conventional
therapies, tumor-bearing cats were treated only with zoledronate on
Day 1, and, if applicable, additional conventional therapies, includ-
ing radiation therapy, chemotherapy, or NSAIDs, were instituted
on Day 2 after collection of serum samples. Whole blood samples
were centrifuged for 10 minutes at 450 g, and serum was separated
and stored at 20 1C in 2-mL polypropylene cryovials until analysis.
Serum VEGF and CTx concentrations were measured by
159
Zoledronate and OSCC
3. commercially available immunoassays,j,l
respectively, both of which
have been previously validated for use in the cat.33,34
Statistical Analysis
To assess the dose-dependent, biologic activity of zoledronate in
the SCCF1 cell line, reductions in soluble VEGF secretion and
RANKL MFI in comparison with untreated cells were evaluated
with a repeated measure ANOVA, and post hoc comparisons were
made with a Tukey-Kramer multiple comparisons test. Differences
in basal serum CTx concentrations between healthy, geriatric, and
OSCC-bearing cats were analyzed by means of a Wilcoxon rank-
sum test. The immediate (o24 hours) effects of zoledronate admin-
istration in OSCC-bearing cats on serum VEGF and CTx
concentrations were analyzed by means of a Student’s t-test and a
Wilcoxon signed-rank test, respectively. Normal distributed data
sets were expressed as mean standard deviation, and nonnormal
distributed data sets were expressed as median and range. All sta-
tistical analysis was performed by commercial computer software.m
Significance was defined as P o.05.
Results
In Vitro Studies
The basal secretion of soluble VEGF by untreated
SCCF1 cells was 632 108 pg/mL after normalization
for differences in cell densities caused by zoledronate ex-
posure. When incubated with zoledronate concentrations
of 3, 10, and 30 mM, SCCF1 secretion of soluble VEGF
concentrations was significantly reduced in comparison
with untreated cells to 449 80, 312 74, and 342
35 pg/mL, respectively (P o.05 for all comparisons). In
addition, zoledronate also influenced the expression of
surface RANKL. Untreated SCCF1 cells expressed
RANKL with a mean fluorescent intensity (MFI) of 24.1
1.7 units. Zoledronate at a concentration of 3 mM qual-
itatively decreased RANKL expression in comparison to
baseline (19.6 1.1 units, P 4.05), whereas zoledronate
at 30 mM significantly increased RANKL expression
above baseline (35.3 1.0 units, P o.01) (Fig 1).
In Vivo Studies
The median basal serum CTx concentration in cats
with bone-invasive OSCC was 601 pg/mL (range 298–
2,260), which was significantly higher than in healthy,
geriatric cats, 336 pg/mL (range 231–642), P 5 .02.
Eight cats with naturally occurring OSCC with con-
firmed bone involvement were treated with zoledronate
(Table 1). The median number of zoledronate treatments
administered to each cat was 1 (range 1–4). For cats re-
ceiving more than a single dose, the median
intertreatment interval was 28 days (range 21–30). In all
8 cats treated with zoledronate, the basal serum VEGF
and CTx concentrations were significantly reduced 24
hours after zoledronate administration. Serum VEGF
concentrations were 124 46.8 pg/mL before treatment
and 74.7 28.6 pg/mL after zoledronate treatment
(P 5 .007) (Fig 2). The average reduction in serum
VEGF concentrations 24 hours after zoledronate treat-
ment was 49.1 37.2 pg/mL. Serum CTx concentrations
were 600.9 pg/mL (range 298–2,260) before and 404 pg/
mL (range 153–1,980) after zoledronate administration
(P 5 .008) (Fig 3). The median reduction in serum CTx
concentrations 24 hours after zoledronate treatment was
170 pg/mL (range 61.3–472).
Discussion
In the current study, we demonstrate that when
SCCF1 cells were exposed to various concentrations of
zoledronate (3–30 mM), the basal secretion of soluble
VEGF was reduced by 30–50%. This finding supports
the anti-angiogenic potential of zoledronate for slowing
the growth of naturally occurring OSCC in cats. Zoled-
ronate’s capacity to attenuate SCCF1’s soluble VEGF
secretion observed in this study is consistent with a pre-
vious report showing a novel nonaminobisphosphonate
Fig 1. Flow cytometric analysis of SCCF1 receptor activator of
nuclear factor KB (NF KB) ligand (RANKL) protein expression.
Modulatory effect of zoledronate on RANKL protein expression in
the SCCF1 cell line. Negative control, isotype staining (thin, dotted
line), basal RANKL expression (thin solid line), zoledronate 3 mM
effect on RANKL expression (cross-hatch), and zoledronate 30 mM
effect on RANKL expression (thick solid line).
Table 1. Study population characteristics: OSCC and healthy,
geriatric cats.
OSCC
(n 5 8)
Healthy, geriatric
(n 5 10)
Age (years)
Median 15 12
Range 8–18 7–15
Weight (kg)
Median 3.3 5.0
Range 2.2–8.8 3.6–7.3
Sex
Female spayed 5 2
Male neutered 3 8
Breed
Domestic shorthair 3 9
Domestic longhair 4 1
Mixed 1 0
Tumor location
Maxilla 3
Mandible 3
Intermandible 1
Lingual base 1
OSCC, oral squamous cell carcinoma.
160 Wypij et al
4. to suppress soluble VEGF secretion from a human
squamous carcinoma cell line.36
The in vitro molecular
mechanism for reduced soluble VEGF secretion after
zoledronate exposure is currently undetermined, but it is
possible that cellular sequestration or isoform shifts may
account for the reduction in soluble VEGF secretion ob-
served in this investigation.
Although the principal antiresorptive mechanism ex-
erted by zoledronate is the induction of osteoclast
apoptosis through inhibition of the mevalonate pathway,
the ability to down-regulate tumor-associated RANKL
expression would also favor bone protection. In this
study, zoledronate at a concentration of 3 mM qualita-
tively reduced the MFI of RANKL in SCCF1, indicating
decreased RANKL protein expression in comparison to
baseline, which would theoretically decrease bone re-
sorption. However, zoledronate at a concentration of
30 mM resulted in an apparent rebound effect, with an
actual increase in MFI of RANKL, which could possibly
enhance bone resorption. These in vitro findings suggest
that a narrow therapeutic window exists for zoledronate
to regulate SCCF1 cell RANKL expression that favors
bone protection. Although it was unexpected that higher
concentrations of zoledronate (30 mM) would induce a
rebound effect for RANKL expression based on flow
cytometric analysis, zoledronate’s potent and direct
osteoclast apoptotic effects are likely to mitigate any en-
hanced bone resorptive consequences associated with
increased tumor cell RANKL expression.
In cats with OSCC, a subpopulation has cancer pain as
a consequence of focal malignant osteolysis. Cancer-
induced bone resorption may increase circulating con-
centrations of collagen type I breakdown products,
which can be assessed in urine and blood, and have
proved to be valuable in monitoring response to anti-
resorptive therapies for human cancer patients.37
Few
studies in companion animals have investigated bone re-
sorption markers and cancer; however, there are
increases in urine N-telopeptide in dogs with append-
icular osteosarcoma.38
Cats in the current study with
histologically confirmed, bone-invasive OSCC had sig-
nificantly higher serum concentrations of CTx than
healthy, geriatric, control cats. One possible explanation
for the increased serum CTx concentration in cats with
OSCC could be the ongoing focal bone destruction with-
in the oral cavity, as has been previously demonstrated in
a small subset of cats that bone-invasive OSCC express
RANKL, a principal mediator for osteoclastogenesis.32
In human patients suffering from skeletal metastases
of breast carcinoma, zoledronate treatment decreases cir-
culating serum VEGF and bone turnover marker
concentrations, changes that correlate with improved
performance status. In the current study, zoledronate
was administered to cats with bone-invasive OSCC, and
attempts were made to verify whether the dose used ex-
erted biologic activity as determined by reductions in
serum VEGF and CTx concentrations within 24 hours
after zoledronate administration. For all cats treated (n
5 8), significant decreases in both serum VEGF and CTx
concentrations were identified after the first dose of
zoledronate, supporting the notion that zoledronate ad-
ministered at a dosage of 0.2 mg/kg IV exerts biologic
activity in OSCC-bearing cats. Interestingly, the magni-
tude of reduction for either serum VEGF or CTx after
zoledronate treatment varied in the 8 cats evaluated, and
could possibly reflect individual differences in biologic
and therapeutic responsiveness to zoledronate treatment.
The reduction in serum CTx concentrations after
zoledronate administration observed in this study was
expected, and most likely attributable to the potent anti-
resorptive effects of zoledronate on both homeostatic
and pathologic bone turnover. Unlike the straightfor-
ward explanation for reduced serum CTx con-
centrations, the potential mechanisms for reduced serum
VEGF concentrations after zoledronate administra-
tion are theoretical and multiple, and could include a
Fig 3. In vivo effects of zoledronate on serum C-telopeptide (CTx)
concentrations. Changes in serum CTx concentrations in cats with
bone-invasive oral squamous cell carcinoma (n 5 8) immediately
before (preZOL) and within 24 hours after (postZOL) treatment
with zoledronate (0.2 mg/kg) administered intravenously. Reduc-
tions in serum CTx concentrations after zoledronate treatment were
statistically significant, P o.05.
Fig 2. In vivo effects of zoledronate on serum vascular endothelial
growth factor (VEGF) concentrations. Changes in serum VEGF
concentrations in cats with bone-invasive oral squamous cell carci-
noma (n 5 8) immediately before (preZOL) and within 24 hours
after (postZOL) treatment with zoledronate (0.2 mg/kg) adminis-
tered intravenously. Reductions in serum VEGF concentrations
after zoledronate treatment were statistically significant, P o.05.
161
Zoledronate and OSCC
5. combination of the following: (1) reduced malignant
osteolysis with subsequent diminished release of bone-
derived TGF-b, a potent promoter of the VEGF gene; (2)
direct attenuation of soluble VEGF release by OSCC
cells as similarly demonstrated in vitro with the SCCF1
cell line; and (3) direct cytotoxicity to OSCC cells, there-
by decreasing the absolute number of tumor cells capable
of releasing soluble VEGF.
Although the findings of this investigation are novel
and important, several limitations should be addressed.
First, the beneficial in vitro effects of zoledronate in re-
ducing soluble VEGF secretion and modulating
RANKL protein expression in the SCCF1 cell line might
not be applicable to natural disease states, because it is
unknown what concentrations of zoledronate are
achieved within the osteolytic tumor micro environment
associated with naturally occurring OSCC. Second, the
maximal attenuation of soluble VEGF by zoledronate
both in vitro (50%) and in vivo (45%) was incom-
plete, and given the large family of angiogenic peptides
that exert redundant activities, partial reductions in only
VEGF might not translate into a meaningful decrease in
cancer cell-induced angiogenesis. Similarly, anti-an-
giogenic effects of novel therapies could require
significant time before measurable responses are ob-
served,39
and given the rapid invasiveness and clinical
morbidity associated with OSCC in cats, any beneficial
anti-angiogenic effects exerted by zoledronate might be
too delayed to alter the natural course of disease. As
such, the evaluation of zoledronate in an inducible xeno-
graft murine tumor model would have provided more
information in determining the biologic relevance of
VEGF attenuation and RANKL modulation in the
SCCF1 cell line. Third, although basal serum CTx con-
centrations were significantly higher in cats with bone-
invasive OSCC when compared with healthy, geriatric
cats, it was not possible to determine whether increased
CTx concentrations could be solely attributed to focal
malignant osteolysis caused by local disease progression
in the oral cavity. Other possibilities that may have ac-
counted for the difference in basal CTx concentrations
between healthy, geriatric, and bone-invasive OSCC-
bearing cats could have been occult endocrine or meta-
bolic disease states associated with increases in global
skeletal resorption, such as hyperparathyroidism, hype-
radrenocorticism, chronic renal insufficiency, and
idiopathic hypercalcemia. Fourth, the number of cats
with bone-invasive OSCC treated with zoledronate was
very small (n 5 8); therefore, strong conclusions regard-
ing the clinical effectiveness of zoledronate cannot be
stated in this study. However, it was not a study objective
to determine whether zoledronate could exert measur-
able clinical effects on naturally occurring OSCC, but
rather the intent was to assess whether single-agent
zoledronate demonstrated theoretical anticancer activi-
ties (anti-angiogenic and antiresorptive), as was
supported by significant reductions in both serum VEGF
and CTx concentrations. Although both serum VEGF
and CTx concentrations were reduced within 24 hours
after zoledronate infusion, we did not evaluate the dy-
namic changes in either serum VEGF or CTx
concentrations as a function of time, and therefore the
maximal duration and magnitude of suppression of these
two surrogate markers could not be determined in this
study. Last, zoledronate has been incriminated in the
rare development of jaw osteonecrosis in human cancer
patients,40
which could mean that its institution in cats
with preexisting mandibular or maxillary bone lesions
might be contraindicated. However, it should be stated
that the exact etiology for bisphosphonate-induced
osteonecrosis remains to be elucidated, but appears to
preferentially develop in human patients treated with
long-term (436 months) antiresorptive therapies. Given
the poor prognosis of bone-invasive OSCC in cats, it is
unlikely that many cats would survive long enough to be
treated with chronic aminobisphosphonate treatment;
thus the potential for developing jaw osteonecrosis
would appear remote.
Despite these limitations, this report provides new in-
formation regarding the bone resorptive characteristics
of naturally occurring OSCC, and is the first description
of serum CTx concentrations in companion animals with
bone-invasive neoplasms. Furthermore, findings from
this study provide in vitro and in vivo evidence to sup-
port future clinical investigations for evaluating
zoledronate in cats diagnosed with bone-invasive OSCC.
Additional prospective studies will be required to define
the clinical effectiveness and long-term tolerability of
zoledronate in both dogs and cats suffering from skeletal
malignancies, and it is hoped that the findings of this
study will provide a conceptual platform for exploring
the use of surrogate markers of bone resorption and ami-
nobisphosphonate treatment for monitoring and treating
painful neoplastic osteolytic processes in companion an-
imals, respectively.
Footnotes
a
Biosource, Rockville, MD
b
Sigma-Aldrich, St Louis, MO
c
Sigma, St Louis, MO
d
Pepro Tech, Rocky Hill, NJ
e
Calbiochem, La Jolla, CA
f
Zoledronate, Basel, Switzerland
g
Axxora Platform, San Diego, CA
h
SCB, Santa Cruz, CA
i
Serotec, Raleigh, NC
j
Quantikine, RD Systems, Minneapolis, MN
k
CellTiter96, Promega, Madison, WI
l
Serum Crosslaps, Nordic Biosciences, Herlev, Denmark
m
GraphPad, Instat3, San Diego, CA
Acknowledgments
The authors would like to thank Jane Chladny and
Lisa Shipp of the Veterinary Diagnostic Laboratory and
Ian Sprandel of the Comparative Oncology Research
Laboratory for their technical assistance.
162 Wypij et al
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