scholarly journals ON CERTAIN SPONTANEOUS CHICKEN TUMORS AS MANIFESTATIONS OF A SINGLE DISEASE

1914 ◽  
Vol 19 (6) ◽  
pp. 570-576 ◽  
Author(s):  
Peyton Rous
Keyword(s):  
Tumor Tissue ◽  
Slow Growth ◽  
Subcutaneous Tissue ◽  
Single Agent ◽  
Clear Fluid ◽  
Small Areas ◽  
Different Strains ◽  
Transplantation Tumors ◽  
Identical Character ◽  
Disease Complexes

Two spontaneous chicken tumors, unlike in several important respects, have given rise on transplantation to neoplasms of identical character. The spontaneous growth, No. 18, situated in the gizzard, was a spindle-celled sarcoma rifted with blood sinuses into which it extended, with result in what may be described as an intracanalicular pattern. The metastases, which were in the voluntary muscles, showed the same peculiar structure. Tumor 38, occurring in the subcutaneous tissue of the groin, was a solid, spindle-celled sarcoma of rather close texture, with few blood vessels. Here and there were small areas of softening, and at its center was a large degeneration cyst with ragged walls, containing a clear fluid. There were no metastases. The transplantation tumors from both growths have been characterized by slow growth, tendency to metastasize to the skeletal muscles without involvement of the lungs, and a structure which at one time is that of a very regular spindle-celled sarcoma containing many bands and ribbons of collagen, and at another that of a sarcoma rifted with blood sinuses like the spontaneous tumor No. 18. At present the two strains are practically indistinguishable in appearance and general behavior. Both are caused by filterable agents. The agent causing No. 38, unlike that causing No. 18, retains its activity in tumor tissue which has been dried or glycerinated; and in a Berkefeld filtrate it is much the more active in causing tumors. These differences can hardly be thought of as constituting a fundamental distinction between agents which, to judge from their effects, are almost undoubtedly different strains of a single disease cause. That chicken tumors of markedly different type have different filterable agents as their cause has been proved by experiments already reported. The present findings make it probable that, within certain limits, tumors of rather various character may be dependent upon a single agent. This assumption greatly simplifies the etiological problem. But the truth of the assumption for other instances than those described in the present article can only be determined by the study and comparison in many hosts of the disease-complexes of which each spontaneous chicken tumor is to be considered as an individual expression.

scholarly journals A First-In-Class, Humanized Antibody Targeting Alternatively Spliced Tissue Factor: Preclinical Evaluation in an Orthotopic Model of Pancreatic Ductal Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Clayton S. Lewis ◽  
Aniruddha Karve ◽  
Kateryna Matiash ◽  
Timothy Stone ◽  
Jingxing Li ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Tissue Factor ◽  
Tumor Tissue ◽  
Single Agent ◽  
The United States ◽  
Ductal Adenocarcinoma ◽  
Boyden Chamber ◽  
Orthotopic Model ◽  
Alternatively Spliced

In 2021, pancreatic ductal adenocarcinoma (PDAC) is the 3rd leading cause of cancer deaths in the United States. This is largely due to a lack of symptoms and limited treatment options, which extend survival by only a few weeks. There is thus an urgent need to develop new therapies effective against PDAC. Previously, we have shown that the growth of PDAC cells is suppressed when they are co-implanted with RabMab1, a rabbit monoclonal antibody specific for human alternatively spliced tissue factor (asTF). Here, we report on humanization of RabMab1, evaluation of its binding characteristics, and assessment of its in vivo properties. hRabMab1 binds asTF with a KD in the picomolar range; suppresses the migration of high-grade Pt45.P1 cells in Boyden chamber assays; has a long half-life in circulation (~ 5 weeks); and significantly slows the growth of pre-formed orthotopic Pt45.P1 tumors in athymic nude mice when administered intravenously. Immunohistochemical analysis of tumor tissue demonstrates the suppression of i) PDAC cell proliferation, ii) macrophage infiltration, and iii) neovascularization, whereas RNAseq analysis of tumor tissue reveals the suppression of pathways that promote cell division and focal adhesion. This is the first proof-of-concept study whereby a novel biologic targeting asTF has been investigated as a systemically administered single agent, with encouraging results. Given that hRabMab1 has a favorable PK profile and is able to suppress the growth of human PDAC cells in vivo, it comprises a promising candidate for further clinical development.

Conservative Management of Uterine Rupture in Gestational Trophoblastic Neoplasia: A Report of 2 Cases

2009 ◽  
Vol 19 (9) ◽  
pp. 1666-1670 ◽  
Author(s):  
Jenny Lynn DC. Estrella ◽  
Agnes L. Soriano-Estrella
Keyword(s):  
Uterine Rupture ◽  
Primary Repair ◽  
Single Agent ◽  
Reproductive Age ◽  
Gestational Trophoblastic Neoplasia ◽  
Small Areas ◽  
Uterine Tumors ◽  
Future Fertility ◽  
Lethal Management ◽  
Desired Family Size

Cases of gestational trophoblastic neoplasia (GTN) with uterine rupture are often catastrophic owing to profuse bleeding, which could be potentially lethal. Management often entails removal of the uterus. Among patients in the reproductive age who have not completed their desired family size, such a procedure could be unacceptable. To address this, uterine resection of localized disease has been performed to preserve fertility. However, in some cases, resection would not leave much of the uterus for future fertility. Hence, primary repair of the rupture could be done. Two cases of uterine rupture in low-risk GTN conservatively managed with primary uterine rupture repair using hemostatic stitches and postoperative single-agent chemotherapy are presented. Both patients were in their early reproductive years and with a great desire to preserve future fertility. The extent of the disease was evaluated in both cases intraoperatively before considering this conservative approach. Such management proved to be effective for both cases. The 2 cases presented are the first reported successful cases in literature on which primary repair of uterine tumor rupture by oversewing with figure-of-eight stitches were done. One should then consider this as a new option in the management of patients who have GTN with uterine rupture, highly desirous of pregnancy, with large uterine tumors but relatively small areas of rupture for which simple stitches would suffice in providing adequate hemostasis.

A Phase II Study of the MEK 1/2 Inhibitor AZD6244 (Selumetinib, ARRY-142866) in Relapsed or Refractory Multiple Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2931-2931
Author(s):  
Beata Holkova ◽  
Ashraf Z. Badros ◽  
Robert Geller ◽  
Peter M. Voorhees ◽  
Adriana Zingone ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Phase Ii ◽  
Research Funding ◽  
Phase Ii Study ◽  
Subcutaneous Tissue ◽  
Single Agent ◽  
Mitogen Activated Protein Kinase ◽  
Response Threshold ◽  
Clinical Activity

Abstract Abstract 2931 AZD6244 is a potent, selective, oral, non-ATP competitive small molecule inhibitor of the mitogen-activated protein kinase, MEK 1/2 that has shown significant pre-clinical activity in multiple myeloma (MM) cells, both in vitro and in vivo, as well as a favorable clinical profile. The present phase II study was designed to determine the response rate for AZD6244 in patients with relapsed or refractory MM. The study utilized a two-stage Simon design to allow for early termination if there was strong evidence of regimen inactivity. Eligible patients were restricted to those with MM who have had at least 2 prior regimens. AZD6244 capsules (75 mg) were administered orally twice daily continuously for 28 day cycles. Response was evaluated after 3 cycles. To date, 37 patients have been enrolled (13 in the 1st stage and 24 in the 2nd stage). One subject enrolled in the 1st stage was not treated. Gender enrollment was balanced (male/female 18/19). The median age of treated patients was 65 years [range 43–81]. ECOG performance scores ranged from 0–2. The median number of prior therapies was 5 [range 2–11]. The most common treatment-related adverse events (occurring in 10–50% of patients) were leukopenia, acneiform rash and other skin/subcutaneous tissue manifestations, fatigue, limb edema, increased aspartate aminotransferase (AST), neutropenia, nausea, facial edema, vomiting, thrombocytopenia, increased creatine phosphokinase, and diarrhea. The most common grade 3 and 4 toxicities (CTCAE v4) included fatigue, peripheral sensory neuropathy, increased AST, neutropenia, nausea, hypotension, thrombocytopenia, increased alanine aminotransferase, and diarrhea. Five deaths have occurred: 2 associated with sepsis, 1 associated with acute kidney injury, all deemed possibly related to AZD6244; and 2 due to disease progression after discontinuation of study treatment. Two objective partial responses have been reported, the first of which justified expansion of the study to the 2nd stage. Twelve patients have had a best response of stable disease, 11 patients have had progressive disease, 1 patient withdrew after cycle 1 (unrelated to toxicity) and did not have response assessed, 3 patients died before response was assessed, and 7 patients are too early to evaluate. Accrual is ongoing to determine if the response threshold in the 2nd stage can be met. Correlative studies are ongoing and are designed to identify potential mechanisms of response/resistance to AZD6244, and to determine the effect of AZD6244 on the bone marrow microenvironment. These include, among others, assessment of pre- and post-treatment expression of phospho-MEK 1/2 and -ERK 1/2, and total levels of Bim. Fifteen patients consented to correlative sampling of bone marrow, blood and/or urine. Results and sample analysis are pending. It is concluded that AZD6244 has modest activity as a single agent in relapsed or refractory MM. This trial also provides a foundation for successor studies employing the MEK 1/2 inhibitor AZD6244 in combination with other agents in patients with MM. Disclosures: Voorhees: Pfizer: Research Funding; Centocor Ortho Biotech: Research Funding; Celgene: Research Funding; MedImmune: Consultancy; Merck: Research Funding.

scholarly journals Primary Adenoid Cystic Carcinoma of the Frontal Sinus: Case Description of a Previously Unreported Entity and Literature Review

2019 ◽  
Vol 98 (4) ◽  
pp. E8-E12 ◽  
Author(s):  
Giancarlo Tirelli ◽  
Vincenzo Capriotti ◽  
Giovanni Sartori ◽  
Margherita Tofanelli ◽  
Alberto Vito Marcuzzo
Keyword(s):  
Adenoid Cystic Carcinoma ◽  
Frontal Sinus ◽  
Perineural Invasion ◽  
Slow Growth ◽  
State Of The Art ◽  
Subcutaneous Tissue ◽  
Free Flap Reconstruction ◽  
Epithelial Tumor ◽  
Adenoid Cystic ◽  
Malignant Epithelial Tumor

Sinonasal adenoid cystic carcinoma is a rare malignant epithelial tumor characterized by slow growth, multiple local recurrences, and perineural invasion; surgery followed by radiotherapy provides the best overall survival by means of an endoscopic, craniofacial, or combined approach. We present a previously undescribed case of frontal sinus adenoid cystic carcinoma involving the subcutaneous tissue and the dura mater treated with an open technique, free flap reconstruction, and hadron therapy together with a summary of the state of the art.

scholarly journals Avelumab for the treatment of relapsed or refractory extranodal NK/T-cell lymphoma: an open-label phase 2 study

Blood ◽  
2020 ◽  
Vol 136 (24) ◽  
pp. 2754-2763 ◽  
Author(s):  
Seok Jin Kim ◽  
Jing Quan Lim ◽  
Yurike Laurensia ◽  
Junhun Cho ◽  
Sang Eun Yoon ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Tumor Tissue ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Complete Response ◽  
Serum Levels ◽  
T Cell Lymphoma ◽  
Phase 2 ◽  
Open Label

Abstract This study aimed to assess the efficacy and safety of treatment with avelumab, an anti–programmed death ligand 1 (PD-L1) antibody, in patients with relapsed or refractory extranodal natural killer/T-cell lymphoma (ENKTL). In this phase 2 trial, 21 patients with relapsed or refractory ENKTL were treated with 10 mg/kg of avelumab on days 1 and 15 of a 28-day cycle. The primary end point was the complete response (CR) rate based on the best response. Targeted sequencing and immunohistochemistry were performed using pretreatment tumor tissue, and blood samples were drawn before and after treatment for measurement of cytokines and soluble programmed cell death protein 1 (PD1), PD-L1, and PD-L2. The CR rate was 24% (5 of 21), and the overall response rate was 38% (8 of 21). Although nonresponders showed early progression, 5 responders currently continue to receive treatment and have maintained their response. Most treatment-related adverse events were grade 1 or 2; no grade 4 adverse events were observed. Treatment responses did not correlate with mutation profiles, tumor mutation burden, serum levels of cytokines, or soluble PD1/PD-L1 and PD-L2. However, the response to avelumab was significantly associated with the expression of PD-L1 by tumor tissue (P = .001). Therefore, all patients achieving CR showed high PD-L1 expression, and their tumor subtyping based on PD-L1 expression correlated with treatment response. In summary, avelumab showed single-agent activity in a subset of patients with relapsed or refractory ENKTL. The assessment of PD-L1 expression on tumor cells might be helpful for identifying responders to avelumab. This trial was registered at www.clinicaltrials.gov as #NCT03439501.

scholarly journals Vulvar Lymphangiosarcoma in a Bitch

2017 ◽  
Vol 45 ◽  
pp. 6
Author(s):  
Isabella De Almeida Fabris ◽  
Marconi Rodrigues De Farias ◽  
Juliana Werner ◽  
Vinicius Gonzales Peres Albernaz ◽  
Taíse Fuchs ◽  
...  
Keyword(s):  
Survival Time ◽  
Subcutaneous Tissue ◽  
Skin Flap ◽  
Young Animal ◽  
Single Agent ◽  
Soft Tissue Sarcomas ◽  
Surgical Excision ◽  
Good Prognosis ◽  
Histological Lesion ◽  
Lesion Pattern

Background: Lymphangiosarcoma (LSA) is a rare, highly malignant and infiltrative neoplasm of the lymphatic endothelium of dogs and cats. It is mostly reported in medium to large breed dogs, over 5-year-old, with no sexual predisposition. Affected animals present fluctuating and diffuse swelling, covering both dermis and subcutaneous tissue, spreading through lymphatic and haematic vessels. Histologically, LSA is characterized by connected channels devoid of conspicuous haematic elements. Treatment depends on location of the neoplasm, staging, and possibility of curative surgical excision. Chemotherapy and radiotherapy can increase survival time. In this report, we describe a rare case of vulvar LSA in a dog. This is the first Brazilian report of LSA in dogs so far.Case: A 3-year-old, female, mixed breed dog was presented for evaluation of vesicle-bullous lesions in the vulvar and perivulvar region with progressive growth along 6 month. Histopathology revealed neoplastic proliferation in the superficial dermis, advancing through the profound dermis. The histological lesion pattern was consistent with angiosarcoma, which united along with macroscopic pattern of the tumor, and the presence of multiple anastomosed vascular structures without erythrocytes within it at microscopy, was compatible with LSA. No evidence of metastasis or lymphadenopathy was found on survey radiography and ultrasound. We performed a surgical excision, and remaining wound was reconstructed with an advancement skin flap. Despite wide surgical resection, neoplastic cells could be found in surgical borders, as well as a metastatic inguinal lymph node. Postoperative chemotherapy based on doxorubicin as a single agent was administrated. Disease free interval (DFI) was one month after surgery, when small bullous lesions were observed near the surgical site, and histopathological exam confirmed LSA. Three months after the surgical procedure, the patient presented with worsening of the lesions, anorexia, and apathy. The owner opted for euthanasia. Total survival time was five months.Discussion: The LSA occurs often in dogs above five years old, unlike this case, in which the patient was 3 years old. Several anatomic locations were cited in other reports. In this case, the lesion was in both the vulvar and perivulvar regions, which is an uncommon location of LSA, described as secondarily affected region in one report only. Despite absence of metastasis in this case, lungs, kidneys, bone marrow, and spleen can be affected. Histopathologic exam is the golden standard for a definitive diagnose of LSA. Diagnosing LSA may be challenging due to its resemblance to hemangiosarcoma, and confirmation is only possible if histopathology detects an absence of red blood cells in the lymphatic channels. Prognosis is poor due to LSA aggressive and infiltrative features. Doxorubicin demonstrated good clinical response in other dogs. Chemotherapy protocols, whether alone or in combination with cyclophosphamide, have been proving to be promising in dogs with soft tissue sarcomas, such as LSA. Surgical approach is the most appropriate and it may be associated with radiotherapy or chemotherapy, especially if complete resection of the tumor is not possible. In this report, even though it was a young animal, the location and extension of the lesion did not contribute to the good prognosis, even after adding adjuvant chemotherapy to the treatment.

The Ultrashort Peptide OW: A New Antibiotic Adjuvant

2019 ◽  
Vol 20 (9) ◽  
pp. 745-754
Author(s):  
Yara Al Tall ◽  
Ahmad Abualhaijaa ◽  
Mohammed T. Qaoud ◽  
Mohammad Alsaggar ◽  
Majed Masadeh ◽  
...  
Keyword(s):  
Synergistic Effects ◽  
Rapid Development ◽  
Single Agent ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Human Blood Cells ◽  
Checkerboard Assay ◽  
Different Strains ◽  
Different Levels ◽  
Mic Value

Background:The over use of current antibiotics and low discovery rate of the new ones are leading to rapid development of multidrug-resistant pathogens worldwide. Antimicrobial peptides have shown promising results against multidrug-resistant bacteria.Objective:To investigate the antimicrobial activity of a new ultrashort hexapeptide (OW).Methods:The OW hexapeptide was designed and tested against different strains of bacteria with different levels of sensitivity. Bacterial susceptibility assays were performed according to the guidelines of the Clinical and Laboratory Institute (CLSI). The synergistic studies were then conducted using the Checkerboard assay. This was followed by checking the hemolytic effect of the hexapeptide against human blood cells and Human Embryonic Kidney cell line (HEK293). Finally, the antibiofilm activities of the hexapeptide were studied using the Biofilm Calgary method.Results:Synergistic assays showed that OW has synergistic effects with antibiotics of different mechanisms of action. It showed an outstanding synergism with Rifampicin against methicillin resistant Staphylococcus aureus; ΣFIC value was 0.37, and the MIC value of Rifampicin was decreased by 85%. OW peptide also displayed an excellent synergism with Ampicillin against multidrug-resistant Pseudomonas aeruginosa, with ΣFIC value of less than 0.38 and a reduction of more than 96% in the MIC value of Ampicillin.Conclusion:This study introduced a new ultrashort peptide (OW) with promising antimicrobial potential in the management of drug-resistant infectious diseases as a single agent or in combination with commonly used antibiotics. Further studies are needed to investigate the exact mechanism of action of these peptides.

A Heparin-Based Inhibitor of Heparanase Blocks Myeloma Growth In Vivo by Targeting the Tumor Microenvironment.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1502-1502
Author(s):  
Yang Yang ◽  
Telisha Swain ◽  
Annamaria Naggi ◽  
Giangiacomo Torri ◽  
Benito Casu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Tumor Tissue ◽  
Single Agent ◽  
Cell Activity ◽  
Dependent Manner ◽  
Myeloma Cells

Abstract Heparanase is an enzyme that cleaves heparan sulfate chains of proteoglycans and promotes the growth and metastasis of many types of human tumors. Our previous work demonstrates that enzymatically active heparanase is present in the bone marrow of myeloma patients and is associated with a poor prognosis, substantially enhances tumor growth and spontaneous metastasis to bone in an animal model of myeloma, and increases the synthesis and shedding of syndecan-1 by myeloma cells, this in turn contributes to myeloma progression by elevating levels of syndecan-1 in the tumor microenvironment. Thus, we hypothesized that inhibitors of heparanase activity would have a dramatic impact on the growth of myeloma tumors. To test this we used a chemically modified form of heparin that is 100% N-acetylated and 25% glycol-split (designated 100NA,RO-H). This form heparin is a potent inhibitor of heparanase enzyme activity but lacks anticoagulant activity thus enabling use of relatively high doses of the drug in vivo. Delivery of the 100NA,RO-H to animals bearing established myeloma tumors dramatically blocked tumor growth and progression in a dose-dependent manner(P<0.04). To understand the mechanism of action of 100NA,RO-H, a series of experiments were performed on tumor tissue harvested from the animals. Results demonstrate that the modified heparin significantly inhibits proliferation of cells within the tumor (33 ± 8/mm2 Ki-67 positive cells in treated vs. 688 ± 164/mm2 positive cells in controls, P = 0.002). 100NA,RO-H also dramatically inhibits angiogenesis as compared to controls as assessed by CD34 staining of tumor tissue. This anti-angiogenic effect may be due at least in part to its regulation of hepatocyte growth factor and/or vascular endothelial growth factor, two angiogenic factors that are detected by immunohistochemistry at high levels in controls but virtually absent from tumors of animals treated with 100NA,RO-H. In vitro studies demonstrate that 100NA,RO-H blocks syndecan-1 shedding from cells, consistent with the role of heparanase in promoting syndecan-1 shedding. In addition, in contrast to our finding that 100NA,RO-H blocks tumor growth in vivo, it only slightly inhibited proliferation, cell cycle progression and growth factor signaling in myeloma cells growing in vitro. Thus, the compound does not appear to have substantial direct effects on tumor cells. Although it is not yet clear if all of the effects of 100NA,RO-H are due to its anti-heparanase activity, we conclude that this modified heparin disrupts the myeloma tumor microenvironment thereby blocking in vivo growth and progression of the cancer. Therefore, its use as a single agent or in combination with agents having direct anti-tumor cell activity may constitute a potent new anti-myeloma therapy.

Neurophysiological effect of 3-cm microwave radiation

1961 ◽  
Vol 200 (2) ◽  
pp. 192-194 ◽  
Author(s):  
Robert D. McAfee
Keyword(s):  
Microwave Irradiation ◽  
Subcutaneous Tissue ◽  
Sensory Nerve ◽  
Nerve Fibers ◽  
Whole Body ◽  
Nociceptive Response ◽  
Small Areas ◽  
Sensory Fibers ◽  
Peripheral Sensory ◽  
Stimulation Of

Neurophysiological effects from locally applied 3-cm microwave irradiation are demonstrated on decerebrate and anesthetized cats and shown to be the result of thermal stimulation of peripheral sensory nerve fibers. The penetrating characteristic of 3-cm radiation heats these fibers within the skin and subcutaneous tissue to 45° ± 2°C at which temperature a nociceptive response is elicited from the experimental animals. The irradiation is applied to small areas of skin or short sections of nerve trunks rich in sensory fibers and the nociceptive response obtained is quite different from the signs of a hyperthermal state seen during whole-body microwave irradiation.

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