Role of Immune Response in the Prognosis of Carcinoma of the Uterine Cervix: Can in Vitro Analysis Provide a better Framework for more Effective Management?

1992 ◽  
Vol 78 (2) ◽  
pp. 87-93 ◽  
Author(s):  
Radhakrishna Pillai ◽  
Prabha Balaram ◽  
M. Krishnan Nair

Cancer of the uterine cervix is the single largest female malignancy in India and also remains a major problem facing oncologists in other parts of the world. While advances in radiation therapy and surgical techniques have made the treatment of cervical carcinoma impressive, limitations to successful management still remain. In fact, the 5-year survival rate, stage for stage, has not improved in the United States or world wide in the past 40 years. With an estimated half a million women developing this disease annually, this lack of improved survival poses an international unresolved health problem. Immune response has been shown to be a major factor involved In the course of the disease for this cancer. Immunologic monitoring was also shown to be of effective value in assessing the prognosis for cervical carcinoma. We studied the various immunologic abnormalities in cervical cancer, the effects of radiation therapy on immune function, prospects of an immunologic staging system, the relationship between human papillomavirus infection and the Immune response, and the possibility of using in vitro Immunologic assessment to provide a better framework for more effective management of cancer of the uterine cervix.

Author(s):  
Andrea Marcellini ◽  
Marco Contoli ◽  
Paolo Casolari ◽  
Sebastian L. Johnston ◽  
Alberto Papi ◽  
...  

1994 ◽  
Vol 4 (2) ◽  
pp. 101-110 ◽  
Author(s):  
R. S. Freedman ◽  
J. M. Bowen ◽  
L. Delcos ◽  
C. L. Edwards ◽  
S. Wallace ◽  
...  

A pilot clinical trial was conducted in patients with squamous carcinoma of the uterine cervix to evaluate the clinical and biologic effects of active intralymphatic immunotherapy (AILI) with allogenic viral oncolysate (VO) prior to radiation therapy. Sixteen patients with advanced primary squamous carcinoma of the uterine cervix and lymph node metastases underwent bipedal intralymphatic injections of VO. VO was derived from lysates of cervical carcinoma cells that had been infected with influenza A virus. AILI was repeated after 2 weeks and followed one week later by standard or extended-field radiation therapy (RT). The first seven patients were treated at one of the three dose levels: 6 mg (three patients), 12 mg (three patients) and 18 mg (one patient). Remaining patients were treated at the 12 mg dose level. Sixteen patients received 63 injections (one patient received three of four doses) of AILI-VO without significant toxicity. Eleven patients have died of persistent or recurrent carcinoma with a total median survival of 19.4 months. Examination of humoral and cellular immunity during AILI-VO showed an increase in the serum liters of antibodies to a surface antigen on cervical carcinoma cells and to the influenza virus. Increased non-MHC restricted lymphocyte cytotoxicity was exhibited by three of four patients treated above the first dose level. Two of the three patients are survivors. By contrast, lymphocytes of patients treated with AILI-VO exhibited either an increase or a decrease in proliferation responses to cervical carcinoma cells. Similarly, post-treatment lymphocytes exhibited either helper or suppressor inducer effects on pre-treatment lymphocytes.


2002 ◽  
Vol 70 (12) ◽  
pp. 6597-6605 ◽  
Author(s):  
María Colmenares ◽  
Stephanie L. Constant ◽  
Peter E. Kima ◽  
Diane McMahon-Pratt

ABSTRACT Recently, a role for B cells in the pathogenesis associated with infection by Leishmania (Leishmania mexicana complex and L. donovani) has been established. In the case of L. mexicana complex parasites (L. mexicana, L. pifanoi, and L. amazonensis), a critical role for immunoglobulin G-mediated mechanisms for the amastigote stage in the host is evident; however, the immunological mechanisms involved remain to be established. In vitro analysis of the kinetics of parasite uptake by macrophages failed to indicate a major effect of antibody opsonization. Given the importance of CD4+ T cells in the development of disease caused by these parasites, the possibility that the lack of pathogenesis was due to the lack of development of an immune response at the local site (draining lymph node and/or cutaneous site) was explored. Interestingly, the level of CD4+-T-cell activation (proliferation and cytokine) in draining lymph nodes from mice lacking circulating antibody (resistant) was found to be comparable to that in nodes from wild-type mice (susceptible) at 2, 5, and 10 weeks postinfection. However, antibody-deficient animals had markedly reduced numbers of monocytes and lymphocytes recruited or retained at the site of cutaneous infection in comparison to wild-type mice, indicating a selective impairment in the local cutaneous immune response. In vitro antigen presentation studies employing tissue-derived (opsonized) amastigotes demonstrated that L. pifanoi-infected FcR−/− macrophages, in contrast to comparably infected wild-type cells, failed to activate Leishmania antigen-specific T lymphocytes. These data, taken together, suggest that one possible mechanism for the role of antibody in pathogenesis may be to mediate parasite uptake and regulate the immune response at the local cutaneous site of infection.


2020 ◽  
Vol 16 (4) ◽  
pp. 276-291
Author(s):  
Adil A. Abbas ◽  
Alaa M.N. Samkari ◽  
Abeer S. Almehdar

Hepatoblastoma (HB) is the most common primary malignant hepatic tumor of childhood and, occurring predominantly in the first two years of life. Approximately 100 cases are diagnosed every year in the United States of America. The management of HB has changed markedly over the last three decades. Alfa feto protein (AFP) and beta human chorionic gonadotrophin (beta HCG) are the main tumor markers and are markers for diagnosis and follow up. International collaborative efforts have led to the implementation of the Pre - Treatment Extent of the Disease PRETEXT staging system consensus classification to assess upfront resectability. Complete surgical resection plays a key role in successful management. Overall, outcomes have greatly improved over the past decades mainly because of advances in chemotherapy (CTR) agents and administration protocols, newer surgical approaches and liver transplantation (LT). Targeted medications towards the newly discovered β-catenin and Wnt genetic pathways in tumor cells may soon become an option for treatment. The current disease free survival (DFS) rates are approaching 85%. For the 25% of patients with metastasis at presentation, the overall survival (OS) remains poor. A more individualized approach to treating the heterogeneous spectrum of HB may become the basis of successful treatment in complex cases. Newer medications and surgical techniques are being exploited. Here we present a comprehensive review of the recent advances in the management of HB. A wide literature search was made using internet search engines such as PubMed and Google scholar. More than 100 articles were reviewed and the information extrapolated was arranged to produce this review.


2021 ◽  
Vol 22 (4) ◽  
pp. 2010
Author(s):  
Wineke Bakker ◽  
Calinda K. E. Dingenouts ◽  
Kirsten Lodder ◽  
Karien C. Wiesmeijer ◽  
Alwin de Jong ◽  
...  

Hereditary hemorrhagic telangiectasia type 1 (HHT1) is a severe vascular disorder caused by mutations in the TGFβ/BMP co-receptor endoglin. Endoglin haploinsufficiency results in vascular malformations and impaired neoangiogenesis. Furthermore, HHT1 patients display an impaired immune response. To date it is not fully understood how endoglin haploinsufficient immune cells contribute to HHT1 pathology. Therefore, we investigated the immune response during tissue repair in Eng+/− mice, a model for HHT1. Eng+/− mice exhibited prolonged infiltration of macrophages after experimentally induced myocardial infarction. Moreover, there was an increased number of inflammatory M1-like macrophages (Ly6Chigh/CD206−) at the expense of reparative M2-like macrophages (Ly6Clow/CD206+). Interestingly, HHT1 patients also showed an increased number of inflammatory macrophages. In vitro analysis revealed that TGFβ-induced differentiation of Eng+/− monocytes into M2-like macrophages was blunted. Inhibiting BMP signaling by treating monocytes with LDN-193189 normalized their differentiation. Finally, LDN treatment improved heart function after MI and enhanced vascularization in both wild type and Eng+/− mice. The beneficial effect of LDN was also observed in the hind limb ischemia model. While blood flow recovery was hampered in vehicle-treated animals, LDN treatment improved tissue perfusion recovery in Eng+/− mice. In conclusion, BMPR kinase inhibition restored HHT1 macrophage imbalance in vitro and improved tissue repair after ischemic injury in Eng+/− mice.


2020 ◽  
Author(s):  
Lin Bai ◽  
Fangchao Jiang ◽  
Renjie Wang ◽  
Chaebin Lee ◽  
Hui Wang ◽  
...  

Abstract Background: Radiation therapy (RT) is a main treatment option for cancer. Due to normal tissue toxicity, radiosensitizers are commonly used to enhance RT. In particular, high-Z nanoparticles, such as gold nanoparticles, have been investigated as radiosensitizers. So far, however, the studies have been focused on gold nanospheres (GNSs). In this study, we assessed the potential of ultra-thin gold nanowires (GNWs) as a radiosensitizer, which is the first time. Results: Our studies showed that GNWs are superior to GNSs with regard to enhancing radical production under radiation. In vitro analysis found that GNWs could stick to the plasma membrane and elevate lipid peroxidation and intracellular oxidative stress under radiation. When tested in vivo , GNWs led to improved tumor suppression by RT relative to GNSs. GNWs may be gradually reduced to form GNSs and shorter gold nanowires, which benefits repeated radiation. Conclusions: Our studies suggest that GNWs are as a promising type of radiosensitizer, which can be safely injected into tumors to enhance radiotherapy. While the current study was conducted in breast cancer models, the approach can be extended to the treatment of other cancers.


Author(s):  
R.A. Milligan ◽  
P.N.T. Unwin

A detailed understanding of the mechanism of protein synthesis will ultimately depend on knowledge of the native structure of the ribosome. Towards this end we have investigated the low resolution structure of the eukaryotic ribosome embedded in frozen buffer, making use of a system in which the ribosomes crystallize naturally.The ribosomes in the cells of early chicken embryos form crystalline arrays when the embryos are cooled at 4°C. We have developed methods to isolate the stable unit of these arrays, the ribosome tetramer, and have determined conditions for the growth of two-dimensional crystals in vitro, Analysis of the proteins in the crystals by 2-D gel electrophoresis demonstrates the presence of all ribosomal proteins normally found in polysomes. There are in addition, four proteins which may facilitate crystallization. The crystals are built from two oppositely facing P4 layers and the predominant crystal form, accounting for >80% of the crystals, has the tetragonal space group P4212, X-ray diffraction of crystal pellets demonstrates that crystalline order extends to ~ 60Å.


Author(s):  
A. Hakam ◽  
J.T. Gau ◽  
M.L. Grove ◽  
B.A. Evans ◽  
M. Shuman ◽  
...  

Prostate adenocarcinoma is the most common malignant tumor of men in the United States and is the third leading cause of death in men. Despite attempts at early detection, there will be 244,000 new cases and 44,000 deaths from the disease in the United States in 1995. Therapeutic progress against this disease is hindered by an incomplete understanding of prostate epithelial cell biology, the availability of human tissues for in vitro experimentation, slow dissemination of information between prostate cancer research teams and the increasing pressure to “ stretch” research dollars at the same time staff reductions are occurring.To meet these challenges, we have used the correlative microscopy (CM) and client/server (C/S) computing to increase productivity while decreasing costs. Critical elements of our program are as follows:1) Establishing the Western Pennsylvania Genitourinary (GU) Tissue Bank which includes >100 prostates from patients with prostate adenocarcinoma as well as >20 normal prostates from transplant organ donors.


2005 ◽  
Vol 173 (4S) ◽  
pp. 315-316
Author(s):  
Kari Hendlin ◽  
Brynn Lund ◽  
Manoj Monga

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