Die Anämie bei malignen Tumorerkrankungen

1989 ◽  
Vol 28 (05) ◽  
pp. 193-200 ◽  
Author(s):  
E. Aulbert

Cellular uptake of 67Ga-labelled transferrin by the tumor tissue was studied in rats with tumors of different malignancy and different tumor mass using the slowly growing Morris hepatoma 5123C, the moderately growing Novikoff hepatoma and the very fast and aggressive Yoshida hepatoma AH130. The cellular accumulation of 67Ga-transferrin was found to correlate with the proliferation activity of the tumor. The 67Ga-transferrin concentration in the very fast growing Yoshida hepatoma was 4.8 times higher than the concentration in the slowly growing Morris hepatoma. The uptake of 67Ga-transferrin by the tumors resulted in a faster disappearance of circulating 67Ga-transferrin from the blood. The rate of disappearance correlated with the proliferation activity and the spread of the tumors. Using tumors of identical size the elimination of 67Ga-transferrin from the blood was much faster in the rats with Yoshida hepatoma than in those with the slowly growing Morris hepatoma. On the other hand, using tumors of different tumor size it could be demonstrated that the rate of disappearance of 67Ga-transferrin from the blood correlated directly with tumor mass. It is concluded that cellular incorporation of transferrin within the tumor cells results in a loss of circulating transferrin, which correlates with tumor mass and proliferation of tumor. This mechanism is supposed to be the cause for the hypotransferrinemia seen in patients with malignant tumors.

1989 ◽  
Vol 28 (06) ◽  
pp. 247-254
Author(s):  
E. Aulbert

The cellular uptake and lysosomal accumulation of 67Ga-labelled transferrin within tumors of different malignancy were examined using tissue fractionation and immunological techniques. As tumor models the slowly growing Morris hepatoma 5123C, the moderately growing Novikoff hepatoma and the fast and aggressive Yoshida hepatoma AH 130 were investigated. Isolation of subcellular fractions of tumor homogenates was performed by differential centrifugation and density-gradient centrifugation. The intracellular 67Gatransferrin was found to be highly concentrated within the purified lysosomes. The transferrin within the lysosomal fraction was identified by radial immunodiffusion technique using monospecific antiserum. The accumulation of 67Gatransferrin by the tumors resulted in a faster disappearance of 67Ga-transferrin from the blood. This loss of circulating 67Ga-transferrin correlated with the proliferation activity and the spread of the tumors. Since transferrin is indispensible for the utilization of iron by the heme-synthesizing red cell precursors, transferrin concentration in the blood is the limiting factor for the utilization of iron in hemoglobin synthesis. Thus, in a further series of experiments we investigated the development of anemia in tumor-bearing rats. With increasing tumor mass a progressive fall of hemoglobin concentration was found. The anemia was more severe in the faster growing Novikoff hepatoma than in the slowly growing Morris hepatoma. The most significant reduction of hemoglobin concentration was found in the very fast growing Yoshida hepatoma. After total tumor resection hemoglobin concentration and red blood cell count normalized completely within 6-8 weeks. We conclude from these data that the uptake of transferrin by the tumor cells results in a faster disappearance of transferrin from the blood. This loss of circulating transferrin correlates with tumor mass and proliferation activity and is one of the factors responsible for the anemia seen in patients with malignant tumors.


1984 ◽  
Vol 68 (1) ◽  
pp. 305-319
Author(s):  
S.J. Goss

‘77orn’, a derivative of the Morris rat hepatoma 7777, stably expresses high levels of ornithine transcarbamoylase (OTC) and carbamoylphosphate synthetase I (CPS-I), and is able to grow indefinitely in ornithine-medium (medium with ornithine in place of arginine). Variants that have lost this ability are isolated from 77orn by a ‘suicide’ selective technique dependent on the cellular incorporation of [3H]ornithine. These variants, which have reduced levels of CPS-I, or of both CPS-I and OTC, are shown to have developed multiple hormonal requirements; their enzyme deficiencies can be reversed by use of an appropriately supplemented medium. In particular, CPS-I is inducible by dexamethasone and dibutyryl-cyclic-AMP in combination. Cholera toxin can be used instead of cyclic-AMP, but then butyrate is additionally required if the induction is to be maintained in the long term. The use of these agents in excess can depress OTC. Several other hepatomas, and alos explanted foetal rat liver cells, have similar requirements for CPS-I expression. It is argued that multiple hormonal requirements for CPS-I production are normal in liver cells in vitro, and that hormone-independent hepatomas should be regarded as abnormal. The implications of this for the somatic cell genetic investigation of differentiation are briefly discussed.


2002 ◽  
Vol 10 (3) ◽  
pp. 164-165
Author(s):  
Natasa Todorovic-Rakovic ◽  
Vesna Ivanovic ◽  
Miroslav Demajo ◽  
Borka Neskovic ◽  
Zora Neskovic-Konstantinovic ◽  
...  

TGF-beta1 is a pluripotent cytokine with diverse effects in the normal development of mammary glands, and in the development of malignant tumors of the breast. The aim of the study was to determine the levels of TGF-beta1 in the group of advanced breast cancer, in which increased TGF-beta1 levels were most likely to be expected. TGF-beta1 levels were also compared with estradiol levels. Our results suggested that TGF-beta1 synthesis may be regulated by estrogen or anti-estrogen through ER. Finding of increased TGF-beta1 levels, due to its possible role in predicting invasive phenotype in later phases of tumor progression, may indicate the tendency of tumor tissue towards autonomy.


2021 ◽  
Author(s):  
Jiongyu Ren ◽  
Xiyuan Zhang ◽  
Jiang Cao ◽  
Jiali Tian ◽  
Jin Luo ◽  
...  

Abstract Background: Long non-coding RNA (lncRNA) HOTAIR was manifested overexpressing and amplifying in many human carcinomas, which could serve as a useful target for cancer therapy. The 99mTc radiolabeled antisense oligonucleotides (ASON) could visualize the expression of HOTAIR and provide a diagnostic and therapeutic value for malignant tumors. The aim of this study was to radiosynthesis 99mTc with HOTAIR ASON and investigate the in vivo imaging in malignant glioma xenografts. Methods: The ASON targeting lncRNA HOTAIR as well as mismatched ASON probe (ASONM) were designed and modified. The radiolabeling of 99mTc with two probes was via the conjugation of bifunctional chelator HYNIC. Then the probes were purified by Sephadex G25 and tested for its radiolabeling efficiency and purity, as well as stability by iTLC and gel electrophoresis. Then the radiolabeled probes were transfected with lipofectamine 2000 for cellular uptake test and the next experimental use. Furthermore, biodistribution study and SPECT imaging was performed at different time after probes were intravenously injected in U87 tumor bearing nude mice models. All data were analyzed by statistical software. Results: The labeling efficiencies of 99mTc-HYNIC-ASON and 99mTc-HYNIC-ASONM measured by iTLC were (91 ±1.5) % and (90 ±0.6) %, respectively, and the radiochemical purity were more than 89%. The probes showed good stability within 12 hours for high radiochemical purity. Gel electrophoresis confirmed that the oligomers were successfully radiolabeled no significant degradation were found. Cellular uptake experiment showed that liposomes had ability to carry probes into cells. Biodistribution study demonstrated that liposome coated 99mTc-HYNIC-ASON had significantly higher uptake in the tumor and higher tumor to muscle ratio than mismatched group. Meanwhile tumor was clearly shown at 1 hours post probe injection of Liposome coated 99mTc-HYNIC-ASON on SPECT/CT imaging, compared with mismatched and blocking group. Conclusion: The Liposome encapsulated 99mTc-HYNIC-ASON probe can be radiosynthesized and used in the in vivo, real-time imaging of lncRNA HOTAIR expression in malignant glioma.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anett Hudák ◽  
Erzsébet Kusz ◽  
Ildikó Domonkos ◽  
Katalin Jósvay ◽  
Alpha Tom Kodamullil ◽  
...  

Abstract Scientific evidence suggests that α-synuclein and tau have prion-like properties and that prion-like spreading and seeding of misfolded protein aggregates constitutes a central mechanism for neurodegeneration. Heparan sulfate proteoglycans (HSPGs) in the plasma membrane support this process by attaching misfolded protein fibrils. Despite of intense studies, contribution of specific HSPGs to seeding and spreading of α-synuclein and tau has not been explored yet. Here we report that members of the syndecan family of HSPGs mediate cellular uptake of α-synuclein and tau fibrils via a lipid-raft dependent and clathrin-independent endocytic route. Among syndecans, the neuron predominant syndecan-3 exhibits the highest affinity for both α-synuclein and tau. Syndecan-mediated internalization of α-synuclein and tau depends heavily on conformation as uptake via syndecans start to dominate once fibrils are formed. Overexpression of syndecans, on the other hand, reduces cellular uptake of monomeric α-synuclein and tau, yet exerts a fibril forming effect on both proteins. Data obtained from syndecan overexpressing cellular models presents syndecans, especially the neuron predominant syndecan-3, as important mediators of seeding and spreading of α-synuclein and tau and reveal how syndecans contribute to fundamental molecular events of α-synuclein and tau pathology.


2020 ◽  
Vol 21 (14) ◽  
pp. 4877
Author(s):  
Kazushige Yoshida ◽  
Masanori Okamoto ◽  
Kaoru Aoki ◽  
Jun Takahashi ◽  
Naoto Saito

Osteosarcoma is one of the most common primary malignant tumors of bone. The combination of chemotherapy and surgery makes the prognosis better than before, but therapy has not dramatically improved over the last three decades. This is partially because of the lack of a novel specialized drug for osteosarcoma, which is known as a tumor with heterogeneity. On the other hand, immunotherapy has been one of the most widely used strategies for many cancers over the last ten years. The therapies related to T-cell response, such as immune checkpoint inhibitor and chimeric antigen receptor T-cell therapy, are well-known options for some cancers. In this review, we offer the accumulated knowledge of T-cell-related immunotherapy for osteosarcoma, and discuss the future of the therapy.


Blood ◽  
2005 ◽  
Vol 105 (7) ◽  
pp. 2757-2763 ◽  
Author(s):  
Rika Okamoto ◽  
Masaya Ueno ◽  
Yoshihiro Yamada ◽  
Naoko Takahashi ◽  
Hideto Sano ◽  
...  

Abstract Hematopoietic cells (HCs) promote blood vessel formation by producing various proangiogenic cytokines and chemokines and matrix metalloproteinases. We injected mouse colon26 colon cancer cells or human PC3 prostate adenocarcinoma cells into mice and studied the localization of HCs during tumor development. HCs were distributed in the inner tumor mass in all of the tumor tissues examined; however, the localization of HCs in the tumor tissue differed depending on the tumor cell type. In the case of colon26 tumors, as the tumor grew, many mature HCs migrated into the tumor mass before fine capillary formation was observed. On the other hand, although very few HCs migrated into PC3 tumor tissue, c-Kit+ hematopoietic stem/progenitor cells accumulated around the edge of the tumor. Bone marrow suppression induced by injection of anti–c-Kit neutralizing antibody suppressed tumor angiogenesis by different mechanisms according to the tumor cell type: bone marrow suppression inhibited the initiation of sprouting angiogenesis in colon26 tumors, while it suppressed an increase in the caliber of newly developed blood vessels at the tumor edge in PC3 tumors. Our findings suggest that HCs are involved in tumor angiogenesis and regulate the angiogenic switch during tumorigenesis.


2017 ◽  
Vol 10 (3) ◽  
pp. 1076-1084 ◽  
Author(s):  
Frank F. Piraino

A 74-year-old female was diagnosed with the autoimmune inflammatory disease temporal arteritis and treated with high and low doses of prednisone over a period of 6 years. During that time, she developed cancers of the lung and colon as well as a soft tumor mass on lumbar vertebrate L3. She also experienced a series of debilitating and disabling symptoms while on prednisone treatment. A temporal analysis of the association of prednisone therapy and immune markers to the successive appearance of the malignant tumors strongly suggests that in the absence of a functioning natural immune and surveillance system by treatment with the immune knockout drug prednisone, spontaneous, multiple independent mutations occurred in several sites in the organ systems of this patient. Over a period of time, these developed into malignant cancers, including a lung nodule which became cancerous 256 days later, as well as the cancers of the colon and a soft tumor mass on lumbar vertebrate L3.


2021 ◽  
Vol 2 (2) ◽  
Author(s):  
Wenny Supit

Abstract: Basosquamous carcinoma (BSCC) is a rare type of skin cancer with an incidence of less than 2% of all skin cancers and the risk of local recurrence ranges between 15% and 50%. We reported a male, aged 57 years old, working as a civil employee, came to the eye clinic with a recurrent BSCC in the right lower palpebral since a month ago. The patient was previously diagnosed as BSCC and had undergone a surgery to remove cancer cells in 2017. However, in 2019, a scan of the axial incision of the head revealed a tumor mass in the right infraorbital area with T4N0Mx. The hypodense structured tumor mass showed increased contrasting. The opera-tive management performed was extensive excision and deep excision with rotational flaps and drainage attached. Histopathological examination of the tumor tissue and excision margins, optic nerve tissue, as well as infraorbital bone tissue indicated a BSCC. Diagnosis of BSCC was confirmed based on anamnesis, physical examination, ophthalmic examination, head CT scan with contrast, and histopathological examination. This case report was aimed to explore BSCC especially in palpebra due to the lack of data of similar cases as well as the potential for diagnosis and promising management.Keywords: basosquamous carcinoma (BSCC), palpebral, reccurent  Abstrak: Karsinoma basoskuamosa (BSCC) merupakan jenis kanker kulit yang langka dengan kejadian kurang dari 2% dari semua jenis kanker kulit namun dengan risiko kekambuhan lokal berkisar 15% dan 50%. Kami melaporkan kasus seorang laki-laki berusia 57 tahun, bekerja sebagai ASN, datang ke klinik mata dengan BSCC palpebra kanan bawah berulang sejak satu bulan lalu. Pasien sebelumnya didiagnosis dengan BSCC dan telah menjalani operasi untuk mengangkat sel kanker pada tahun 2017. Namun, pada tahun 2019, pemindaian kepala sayatan aksial menunjukkan adanya massa tumor di area infraorbital kanan dengan T4N0Mx. Massa tumor berstruktur hipodens dengan kontras yang meningkat. Manajemen operatif dilakukan eksisi ekstensif dan eksisi dalam dengan flap rotasi dan drainase terpasang. Pemeriksaan histopatologik dilakukan terhadap jaringan tumor dan margin eksisi, jaringan saraf optik, serta jaringan tulang infraorbital dengan simpulan suatu BSCC. Pada kasus ini diagnosis BSCC ditegakkan berdasarkan anamnesis, pemeriksaan fisik, pemeriksaan oftalmologi, pemeriksaan penunjang berupa CT scan kepala dengan kontras, dan pemeriksaan histopatologik. Laporan kasus ini bertujuan untuk mendalami BSCC khususnya di palpebra karena minimnya data mengenai kasus yang serupa, serta potensi diagnosis dan penatalaksanaan yang menjanjikannya.Kata kunci: karsinoma basoskuamosa (BSCC), palpebra, rekuren


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