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47 results about "Tumor burden" patented technology

Tumor burden. tu·mor bur·den. the total mass of tumor tissue carried by a patient with a malignancy. tu·mor bur·den. The total mass of tumor tissue carried by a patient with cancer. Synonym(s): tumour burden. tumor burden. The sum of cancer cells present in the body.

Recombinant complement protein and application thereof in preparation of anti-leukemia drugs

ActiveCN120590505APeptide/protein ingredientsAnimals/human peptidesChemotherapy combinationsAcute leukemia
The invention relates to a recombinant complement protein and application thereof in preparation of anti-leukemia drugs, and belongs to the technical field of biological medicines. The invention discloses a method for treating acute leukemia by single drug, namely injecting recombinant C1QBP protein, which has a remarkable effect on treating acute leukemia, can be used for remarkably inhibiting proliferation of leukemia cells in marrow, spleen and peripheral blood of a hematopoietic system and also inhibiting infiltration of the leukemia cells in extramedullary organs (skin and the like), so that the whole-body tumor load is reduced, and the curative effect of treating acute leukemia is improved. The lifetime of leukemia mice is obviously prolonged. The recombinant C1QBP protein is combined with a clinical first-line chemotherapy regimen for use, has a synergistic effect, has a stronger effect of inhibiting leukemia cell proliferation compared with a single chemotherapy drug, can significantly prolong the lifetime of leukemia mice, and plays a role in reducing toxicity and enhancing efficacy. The invention proves that the complement C1Q binding protein has the effect of treating leukemia for the first time, provides a preparation method and a drug combination scheme, and has relatively high clinical transformation prospect and application value.
Owner:XIN HUA HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE

Application of CD40 antibody in preparation or screening of multiple myeloma bone disease products

The invention discloses a therapeutic target CD40 related to multiple myeloma bone diseases and application of a monoclonal antibody of the therapeutic target CD40. On one hand, it is found that formation and osteogenic differentiation of primary cilia of BMSCs can be effectively recovered by adding a CD40 neutralizing antibody into an MM-BMSCs co-culture system; on the other hand, the CD40 neutralizing antibody is found to reduce bone destruction and tumor load in a Vk * MYC myeloma mouse model. CD40 is expected to become a potential target spot for treating multiple myeloma bone diseases and has a very wide application prospect in the field of medical research.
Owner:SHANDONG RES INST OF TUMOUR PREVENTION TREATMENT

Method of treating cancer

Disclosed herein is a method of treating patients with NSCLC subtypes of cancer by reducing tumor burden, comprising administering at least one dose of purified Ruthenium (III) Pyrazole complexes to patients suffering from NSCLC, wherein said dose is therapeutically sufficient. In one or more embodiments, the Ruthenium III Pyrazole is RuCl3(DMSO)(dmPyz)2.
Owner:UNIVERSITY OF LOUISIANA AT LAFAYETTE

Genomic biomarker prediction from medical images

ActiveUS12347559B2Image enhancementMedical data miningGenomic BiomarkerNerve network
A method, apparatus, and non-transitory computer-readable medium are provided for image processing of medical images. The method may include receiving one or more medical images. Tissue regions may be identified in each of the one or more medical images. The method may include generating patches associated with respective identified tissue regions. A patch tumor burden (TMB) score may be predicted for each of the patches based on a neural network model, wherein the neural network model is trained using a distribution smoother and a weighted loss function. The method may also include a tumor burden score being generated for each of the one or more medical images based on the patch tumor burden score for patches associated with the respective identified tissue regions in respective medical images from the one or more medical images.
Owner:RAKUTEN GROUP INC

Phytobacterium plantarum AR195 and application thereof in preparation of medicine for preventing and / or treating lung cancer

The invention discloses a plant lactobacillus AR195 strain and application thereof in preparation of a medicine for preventing and / or treating lung cancer, and belongs to the technical field of microorganisms. Through verification, the plant lactobacillus AR195 can inhibit the growth of lung cancer cells, also has certain prevention and treatment effects in a lung cancer mouse model, and can reduce the tumor burden of a BALB / c mouse lung cancer model by reducing MMP9 secretion, so that the plant lactobacillus AR195 can be used for preventing and assisting in treating lung cancer. Meanwhile, the accumulation of the AR195 bacteria in the lung can be improved to the maximum extent through atomization administration, and meanwhile, the adverse side effects of the whole body are reduced. A new drug source is provided for treatment of lung cancer, a novel treatment strategy is provided for treatment of lung cancer by probiotics, and treatment of lung cancer and development of a novel treatment method are facilitated. Meanwhile, the application range of the plant lactobacillus AR195 strain is widened, and a novel treatment strategy is provided for a potential mechanism of treating lung cancer by probiotics.
Owner:UNIV OF SHANGHAI FOR SCI & TECH

Animal models of CAR-T therapy for leukemia complicated by cytokine release syndrome, their preparation methods and applications

This invention relates to the field of leukemia research, specifically disclosing an animal model of CAR-T therapy for leukemia complicated by cytokine release syndrome (CRS), its preparation method, and its application. The method for preparing the animal model of CAR-T therapy for leukemia complicated by CRS includes: obtaining CD19 CAR-T cells: peripheral blood mononuclear cell isolation, T cell magnetic bead sorting, T cell activation, lentiviral infection, and CAR-T cell expansion; constructing an animal model of CRS after high- and low-dose CAR-T infusion: implanting Nalm-6 cell line into living animals to induce leukemia tumor burden, obtaining living animals with leukemia tumor burden, and injecting CD19 CAR-T cell line into the living animals with leukemia tumor burden. This invention provides a novel application for the animal model of CAR-T therapy for leukemia complicated by cytokine release syndrome. By using severely combined immunodeficient mice and inoculating them with high- and low-burden tumor cells, and infusing different doses of CAR-T cells, this invention constructs an in vivo model that can simulate clinical CRS, providing research guidance for clinically exploring more effective interventions.
Owner:XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV

Methods and systems for detecting colorectal cancer by nucleic acid methylation analysis

ActiveCN115667554BEnsemble learningNucleotide librariesCell freeColorectal disease
The present disclosure provides methods and systems for screening or detecting colorectal cancer or subsequent colorectal disease progression, which can be applied to cell-free nucleic acids, such as cell-free DNA. The methods can train a machine learning model using detection of methylation signals within single sequencing reads in identified genomic regions as input features, and generate a classifier suitable for stratifying a population of individuals. The methods can include extracting DNA from a cell-free sample obtained from a subject, transforming the DNA for methylation sequencing, generating sequencing reads, and detecting colon proliferative cell disorder related signals in the sequencing information, and training a machine learning model to provide a discriminator capable of distinguishing between groups such as healthy, cancer, etc. in a population of subjects, or distinguishing between disease subtypes or stages. The methods can be used, for example, to predict, prognosticate, and / or monitor response to treatment, tumor burden, recurrence, or progression of colorectal cancer.
Owner:FREENOM HLDG INC

Application of A. muciniphila bacteria and outer membrane vesicles thereof in relieving chronic stress-mediated colorectal cancer progress

PendingCN120241801ADigestive systemUnknown materialsMurine tumorInvasion metastasis
The invention belongs to the technical field of biological medicines, and relates to an A.muciniphila bacterium and an application of an outer membrane vesicle of the A.muciniphila bacterium in relieving chronic stress-mediated colorectal cancer progress. The product provided by the invention can effectively improve the influence of chronic stress on the tumor growth of colorectal cancer mice, and specifically comprises the following steps: inhibiting and / or relieving weight loss, relieving intestinal function damage, relieving tumor load increase, reducing tumor cell proliferation activity, and relieving or inhibiting the growth, invasion and metastasis of tumors. The invention provides a new treatment strategy for colorectal cancer patients accompanied by chronic stress.
Owner:CHENGDE MEDICAL UNIV

Probe set for judging triple negative breast cancer systemic tumor burden and application thereof

The present disclosure provides a probe set for judging the systemic tumor burden of triple-negative breast cancer and application thereof, the probe set provided by the present disclosure can be used for detecting the gene markers of triple-negative breast cancer and for evaluating the systemic tumor burden, and can achieve good coverage and capture of the target region, obtain sufficient read information on the target region, and overcome the spatial and temporal heterogeneity of tumors to a certain extent, while improving the capture efficiency, stabilizing the experimental system, and meeting the requirements of clinical detection.
Owner:SUN YAT SEN MEMORIAL HOSPITAL SUN YAT SEN UNIV +1

ASO inhibitor of CREPT gene and inhibition of ASO inhibitor on liver cancer

The invention provides an antisense oligonucleotide (ASO), the antisense oligonucleotide is complementary with a CREPT gene sequence, the expression of CREPT can be effectively inhibited, and the antisense oligonucleotide is selected from antisense oligonucleotides with any one nucleotide sequence as shown in SEQ ID No.1-3. The antisense oligonucleotide (ASO) can efficiently and specifically target CREPT, the expression level of CREPT in tumor cells is significantly reduced, the clone formation ability of the tumor cells is further reduced, and the invasion ability of the tumor cells is significantly reduced. The invention further provides an extracellular vesicle and a pharmaceutical composition, and tumor load can be remarkably reduced after the extracellular vesicle is applied to a patient. The antisense oligonucleotide (ASO) of the invention can be used for treating liver cancer.
Owner:HEYA (BEIJING) PHARMACEUTICAL TECHNOLOGY CO LTD

Cells expressing anti-CD70 chimeric receptors and uses thereof

The presently disclosed subject matter provides cells, compositions, and methods for enhancing immune responses to tumor antigens. These cells comprise a first antigen-recognizing receptor that targets CD70. These cells have improved activity and / or efficiency. The present invention also provides a method for reducing tumor burden in a subject with renal cell carcinoma, pancreatic cancer, or ovarian cancer, comprising administering to the subject an effective amount of cells comprising a TCR-like fusion molecule that targets CD70.
Owner:MEMORIAL SLOAN KETTERING CANCER CENT +2

Combination therapy with angiogenesis protein and immune checkpoint inhibitor with / without chemotherapeutics

Provided are pharmaceutical compositions for reducing a tumor burden in a subject having a cancer comprising a combination therapy comprising a therapeutically effective dose of a modified CD2 polypeptide derived from human or rat domain one of CD2 polypeptide and a second therapeutic agent comprising an immune checkpoint inhibitor. Also provided are methods of inhibiting or reducing tumor growth and methods of synergistically increasing the activity of an anti-PD-L1 immunotherapeutic in a subject having a cancer comprising administering the pharmaceutical compositions.
Owner:GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC

Systemic biomarkers for the dynamic assessment of tumor burden and treatment efficacy in high grade gliomas

PendingUS20260188489A1Tumor LoadBiologic marker
Embodiments of the present disclosure pertain to methods of assessing glioma in a subject by (1) receiving a plurality of measured biomarker levels of the subject; and (2) assessing glioma in the subject based on the measured biomarker levels by at least correlating differentially expressed levels of the measured biomarkers to at least one of (a) diagnosis of glioma, (b) progression of glioma, (c) treatment outcome, and / or (d) tumor burden. The methods of the present disclosure also include a step of (3) making a treatment decision based on the assessment. Additional embodiments of the present disclosure pertain to systems for assessing glioma in a subject.
Owner:TRUSTEES OF DARTMOUTH COLLEGE THE +1

Neoadjuvant cancer treatment

PendingUS20250241969A1SsRNA viruses positive-senseMicrobiological testing/measurementPoliomyelitisPoliovirus
Provided is a method of treating a tumor in an individual by neoadjuvant therapy, wherein the individual has not previously undergone treatment to effectively reduce tumor burden, the method comprising administering an oncolytic chimeric poliovirus construct, or an oncolytic chimeric poliovirus construct and an immune checkpoint inhibitor, followed by reduction of the tumor. The method may further comprise administration of immune checkpoint inhibitor or oncolytic chimeric poliovirus construct following reduction of tumor. Kits for performing the methods are also provided.
Owner:DUKE UNIV

Use of ampakine compounds for the preparation of a medicament for the treatment of gastric cancer peritoneal metastasis

This invention relates to the application of AMPA receptor antagonists in the preparation of drugs for treating peritoneal metastases of gastric cancer, belonging to the field of biomedical technology. This invention discloses the application of GRIA2 as a drug target in the preparation of drugs for the prevention or treatment of peritoneal metastases of gastric cancer. It discloses the use of AMPA receptor antagonists NBQX and / or Selurampanel in the preparation of drugs for the prevention or treatment of peritoneal metastases of gastric cancer. NBQX and Selurampanel can significantly inhibit the migration, invasion, spheroidization ability, and adhesion to mesothelial cells of gastric cancer cells; in vivo experiments have confirmed that AMPA receptor antagonists can significantly reduce tumor burden and the number of metastatic nodules in a mouse model of peritoneal metastases of gastric cancer. Patient-derived organoid xenograft models further demonstrate that AMPA receptor antagonists have significant efficacy against peritoneal metastases of gastric cancer with high GRIA2 expression. This invention provides a new treatment strategy for peritoneal metastases of gastric cancer.
Owner:ZHONGSHAN HOSPITAL FUDAN UNIV

PSMA-positive extracellular vesicles as a predictive biomarker of response to radiotherapy in advanced prostate cancer

The present disclosure provides materials and methods for assessing and / or treating subjects having prostate cancer. In some embodiments, materials and methods for assessing a subject's tumor burden using a liquid biomarker, tumor-derived extracellular vesicle expressing a surface antigen, are provided. Provided are materials and methods for using the presence or absence of the biomarker to assess whether a subject should be treated with radiotherapy alone, or whether the subject would benefit from systemic therapy, either alone or in combination with radiotherapy.
Owner:MAYO FOUNDATION FOR MEDICAL EDUCATION & RESEARCH

Method for inhibiting tumor cell proliferation by knocking down CREPT through siRNA

The invention discloses siRNA (small interfering Ribonucleic Acid) for inhibiting the expression of a CREPT gene. The nucleotide sequence of a positive-sense strand of the siRNA is shown as any one of SEQ ID No. 1 to SEQ ID No. 3. The siRNA can be used for inhibiting CREPT (Cathode Reactive Part of siRNA can inhibit the growth of mouse colon cancer cells and the growth of NIH3T3 fibroblast cells. And the drug can be delivered through the liposome of the delivery system si-CREPT, so that the mouse liver cancer can be treated, and the tumor load of the mouse liver cancer can be remarkably reduced.
Owner:HEYA (BEIJING) PHARMACEUTICAL TECHNOLOGY CO LTD

Cxcl10 binding proteins and uses thereof

The present invention relates to C-X-C motif chemokine ligand 10 (CXCL10) binding proteins and their use in methods of detecting and / or diagnosing a condition in a subject, including determining the level of CXCL10 in a subject. Specific antibodies that bind total CXCL10 (full length, N-terminally truncated and citrullinated) and antibodies that bind active CXCL10 (full length) are used to measure the level of total CXCL10 and active CXCL10 in ovarian cancer patient samples. The calculated ratio between active CXCL10 and total CXCL10 is lower in patients with malignant disease compared to patients with benign tumors or healthy individuals, and this calculated ratio is the basis for methods of diagnosing malignant disease, monitoring tumor burden and disease progression.
Owner:HUDSON INST OF MEDICAL RES

Machine learning guided signal enrichment for ultrasensitive plasma tumor burden monitoring

Systems, methods, and computer program products are provided for diagnosing, prognosing, or monitoring cancer in a subject, particularly the assessment of minimal residual disease (MRD).
Owner:MEMORIAL SLOAN KETTERING CANCER CENT +2

Application of BAHD1 as target spot in preparation of leukemia treatment medicine

ActiveCN121041446AOrganic active ingredientsAntineoplastic agentsExtramedullary infiltrationApoptosis
The invention relates to application of BAHD1 as a target spot in preparation of leukemia treatment drugs, and belongs to the technical field of biological medicines. In order to solve the ubiquitous problems of high drug resistance and high recurrence of acute leukemia treatment schemes, the invention provides application of BAHD1 as a target spot in preparation of leukemia treatment drugs. The invention proves that BAHD1 is highly expressed in acute leukemia cells and is used as a molecular marker for diagnosis of acute leukemia. The invention proves that the knockout of BAHD1 significantly inhibits proliferation and self-renewal of acute leukemia cells and promotes apoptosis and differentiation of the acute leukemia cells; the proliferation of in-vivo leukemia cells is effectively inhibited, the tumor load and extramedullary infiltration are reduced, and the lifetime is remarkably prolonged. In addition, by knocking out BAHD1, the sensitivity of acute leukemia cells to traditional chemotherapeutic drugs and targeted therapeutic drugs can be remarkably enhanced.
Owner:HARBIN MEDICAL UNIVERSITY

Systems, compositions, and methods for target entity detection

ActiveUS12674190B2DiseaseEfficacy
The present disclosure provides technologies for target entity detection. One aspect of the present disclosure provides technologies for detection (e.g., early detection) of a disease, disorder, or condition (e.g., cancer). In another aspect, technologies provided herein are useful for selecting and / or monitoring and / or evaluating efficacy of, a treatment administered to a subject in need thereof, e.g., a subject determined to have or susceptible to cancer. In some embodiments, technologies provided herein are useful for development of companion diagnostics, e.g., by measuring tumor burdens and changes in tumor burdens in conjunction with therapeutics.
Owner:MERCY BIOANALYTICS INC

Methods of treatment using BCN057 and BCN512

The present disclosure is directed to methods of treating or ameliorating various conditions by the administration of a BCN057, BCN512 or analogs of these compounds. The compounds can be used to reduce tumor burden in cancers, including pancreatic cancer and gastrointestinal (GI) cancer. The compounds can also be used to protect against chemotherapy induced toxicity to the GI tract. Further, they can be used to treat fibrosis and various inflammatory conditions. Analogs of BCN057 and BCN512 are also described.
Owner:BCN BIOSCIENCES LLC

Compositions and methods for detection of liver cancer

The present disclosure in one aspect provides technologies for detection of liver cancer, e.g., early detection of liver cancer. In another aspect, technologies provided herein are useful for selecting and / or monitoring and / or evaluating efficacy of, a treatment administered to a subject determined to have or susceptible to liver cancer. In some embodiments, technologies provided herein are useful for development of companion diagnostics, e.g., by measuring tumor burdens and changes in tumor burdens in conjunction with therapeutics. In some embodiments, technologies provided herein are useful for development of companion diagnostics, e.g., by identifying biomarkers in subjects' bodily fluid samples (e.g., blood samples) that are associated with therapeutic response.
Owner:MERCY BIOANALYTICS INC

Methods of treating adrenal tumor

PendingCN121194781AOrganic active ingredientsCapsule deliveryBenign Adrenal NeoplasmAcyl group
Methods and uses are disclosed for treating an adrenal tumor in a subject suffering from an adrenal tumor to reduce the size or tumor load of the adrenal tumor, prevent its growth, or slow its growth, or reduce or alter its secretion, or induce its degeneration or apoptosis. The novel methods of treatment include the use or administration of an effective amount of a glucocorticoid receptor modulator (GRM) compound having a heteroaryl-ketone fused aza-naphthane structure to a patient suffering from an adrenal tumor. The adrenal tumor may be a benign adrenal tumor. In some embodiments, GRM may be reracolan, which is ((R)-(1-(4-fluorophenyl)-6-((1-methyl-1H-pyrazol-4-yl) sulfonyl)-4, 4a, 5, 6, 7, 8-hexahydro-1H-pyrazolo [3, 4-g] isoquinolin-4a-yl) (4-(trifluoromethyl) pyridin-2-yl) methanone). The GRM may be administered orally. The GRM may be administered with a food. The treatment methods can be used before, during or after an adrenal tumor operation, and can also be used without an operation. The use of these therapeutic methods may not adversely affect normal adrenal gland tissue.
Owner:CORCEPT THERAPEUTICS INC

Systems and methods for detecting tumor development

This patent discloses a method for detecting a patient's tumor burden. DNA is extracted from a patient's tumor tissue sample, a predetermined number of biomarker genes are selected to form a biomarker gene cluster ("customized gene cluster"). A DNA sample of circulating free cells in the patient's body fluid is isolated. DNA sequences containing biomarker genes are enriched in the free DNA fragments. The enriched DNA is sequenced. The mutant and normal DNA sequences in the enriched DNA are counted. The patient's tumor burden is then determined. Preferably, mutations in therapeutically relevant genes ("drug-targeted genes") are detected simultaneously with the detection of the customized gene cluster.
Owner:CARRIER GENE TECH SUZHOU CO LTD +1

Compositions and methods for detection of ovarian cancer

The present disclosure in one aspect provides technologies for detection of ovarian cancer, e.g., early detection of ovarian cancer. In another aspect, technologies provided herein are useful for selecting and / or monitoring and / or evaluating efficacy of, a treatment administered to a subject determined to have or susceptible to ovarian cancer. In some embodiments, technologies provided herein are useful for development of companion diagnostics, e.g., by measuring tumor burdens and changes in tumor burdens in conjunction with therapeutics. In some embodiments, technologies provided herein are useful for development of companion diagnostics, e.g., by identifying biomarkers in female subjects' bodily fluid samples (e.g., blood samples) that are associated with therapeutic response. In some embodiments, technologies provided herein are useful for differentiating a benign adnexal mass from ovarian cancer.
Owner:MERCY BIOANALYTICS INC

Preparation and application of oncolytic virus specifically promoting tumor cytoplasmic membrane rupture

PendingCN122357462ATherapeutic effectCytoplasm
This invention relates to the preparation and application of an oncolytic virus that specifically promotes the rupture of tumor cell plasma membranes. Specifically, this invention utilizes a glioblastoma-specific Nestin enhancer or a tumor cell-specific Survivin promoter to drive the specific expression of the NINJ1 or DTA gene, thereby enhancing the lytic and killing ability of cells. The oncolytic virus G005 expressing NINJ1 exhibits strong killing ability against tumor cells, and the tumor completely disappears in an orthotopic glioma animal model. It can also rapidly restore the weight loss in mice caused by tumor burden, demonstrating that the oncolytic virus G005 has excellent therapeutic effects against GBM.
Owner:JINAN UNIVERSITY

Compositions and methods for detection of lung cancer

The present disclosure in one aspect provides technologies for detection of lung cancer, particularly early detection of lung cancer. In another aspect, technologies provided herein are useful for selecting and / or monitoring and / or evaluating efficacy of, a treatment administered to a subject determined to have or susceptible to lung cancer. In some embodiments, technologies provided herein are useful for development of companion diagnostics, e.g., by measuring tumor burdens and changes in tumor burdens in conjunction with therapeutics. In some embodiments, technologies provided herein are useful for development of companion diagnostics, e.g., by identifying biomarkers in a subject's bodily fluid samples (e.g., blood-derived samples) that are associated with therapeutic response.
Owner:MERCY BIOANALYTICS INC

Pharmaceutical composition for treating colitis or colorectal cancer comprising colon-targeted s100a8 / a9-derived specific peptide

The present invention relates to a dual PRR-inhibiting peptide system consisting of TLR4- and RAGE-inhibiting motifs derived from S100A8 and S100A9 and conjugated with a CT peptide for colon-specific delivery. In human-derived monocyte THP-1 and mouse bone marrow-derived macrophages (BMDMs), S100A8 / A9-derived peptides including TLR4 and RAGE-interacting motifs inhibit the binding of S100 to TLR4 or RAGE and the activation of the NLRP3 inflammasome in a dose-dependent manner. When the peptide according to the present invention is injected into mouse models of acute and chronic colitis, survival is significantly increased, and pathological damage to the colon is alleviated. In a mouse model of colitis-related colorectal cancer, when the peptide according to the present invention is injected, body weight is increased, tumor burden in the distal colon is decreased, and histological colon damage is significantly alleviated. When the peptide according to the present invention is injected into an oxaliplatin-resistant CRC xenograft mouse model, EMT-associated markers are reduced in tumor tissues and tumor growth is significantly inhibited.
Owner:IND UNIV COOP FOUND HANYANG UNIV ERICA CAMPUS

Cells and compositions for treating cancer

The presently disclosed subject matter provides cells, compositions, and methods for enhancing immune responses to tumor antigens. These cells comprise a first antigen-recognizing receptor (e.g., a chimeric antigen receptor (CAR)) and a second antigen-recognizing receptor (e.g., a TCR-like fusion molecule). These cells have improved activity and / or efficiency. The presently disclosed subject matter further provides uses of these compositions in reducing tumor burden, treating and / or preventing neoplasms or tumors, preventing and / or treating pathogen infections, preventing and / or treating autoimmune diseases, and / or preventing and / or treating infectious diseases.
Owner:MEMORIAL SLOAN KETTERING CANCER CENT +2