Tumor Immunology

Tumor microenvironment (TME) is a host for a complex network of heterogeneous stromal cells with overlapping or opposing functions depending on the dominant signals within this milieu. Reciprocal paracrine interactions between cancer cells with cells within the tumor stroma often reshape the TME in favor of the promotion of tumor. These complex interactions require more sophisticated approaches for cancer therapy, and, therefore, advancing knowledge about dominant drivers of cancer within the TME is critical for designing therapeutic schemes. This review will provide knowledge about TME architecture, multiple signaling, and cross communications between cells within this milieu, and its targeting for immunotherapy of cancer.

Global Tumor Ablation Market Forecast & Regional Analysis 2023” Report Highlights:

• Exploring the Commercial Aspects of Tumor Ablation Therapy
• Recent Advances in Tumor Ablation Therapy
• Demand & Features of the Tumor Ablation Therapy
• Technological Aspect of Tumor Ablation Therapy
• Technology, Devices & Tools Involved in Tumor Ablation Therapy
• Clinical Status of Tumor Ablation Therapy in Various Cancer Types
• Global Tumor Ablation Therapy Market by Region, Technology & Mode of Treatment

Secondary immunodeficiency’s, previously presented in immunocompetent individuals. The lack of primary or secondary response to the presence of a foreign antigen, in the case of infections is a sentinel data in the diagnosis of immunodeficiency (can be primary or secondary), in the case of a self antigen may generate the presence of Cancer. Cancer has shown an increase in the prevalence and incidence globally. Most current medical treatments in cancer are focused primarily on immunomodulatory actions (immunosuppression / immune stimulation or both). Knowledge of key concepts from the perspective of innate andacquired immunity lead to cancer development, engaging immune surveillance and escape mechanisms of this that contribute to better understand the origin, behavior and treatment of neoplasm’s. These treatments can cause immunological disorders such as allergy, anaphylaxis

According to the WHO, cancer has taken away the lives of an estimate of 9.6 million people in 2018 globally. 1 in 6 deaths worldwide is caused by cancer, making it the second leading cause of death (WHO, 2018). This malignant disease is characterized by an uncontrollable proliferation of the patient's own cells due to the activation of a tumor-initiating gene or the inhibition of a tumor-suppression gene. Such an activation or inhibition is usually triggered by external pressures, including radiation and viral infections, or internal pressures such as innate genetic predispositions. Knowing that cancer may occur in any cell capable of replication, one extremely fatal type of cancer which is sweeping nations worldwide is lung cancer. Throughout the past 40 years, despite the exorbitant amount of research invested, the overall survival rate of the major type of lung cancer has merely increased from 14% to 18%, and this statistic still holds true for today (Ron Chen, 2014). In 2018, out of the 2.09 million cases of lung cancer worldwide, only 330,000 individuals have survived their battle with cancer, which means that 84% of these cases died (WHO, 2018). Also, it is pivotal to keep in mind that lung cancer, in specific, has numerous risk factors. One factor that is exceptionally prevalent in our Lebanese society is smoking (Tobacco products), which not only affects smokers themselves, but also the people around them who are affected by secondhand smoke. Further influences include air pollution (Garbage crisis in Lebanon), exposure to asbestos, arsenic, and radiation. Therefore, lung cancer's inefficient
treatments, coupled with its extremely poor prognosis and prolific risk factors, affirm the need for a new approach for treatment.

It is generally accepted that human and experimental tumor cells can lose major histocompatibility complex (MHC) class I molecules. These human leukocyte antigen (HLA) losses are detected when the primary tumor breaks the basal membrane, invades the surrounding tissues, and starts to metastasize. These altered HLA class I phenotypes probably constitute the major tumor escape mechanism facing anti-tumor T-cell mediated responses. Thus, it is important to characterize these phenotypes in clinical tumor samples, analyze the mechanism(s) responsible for them, and counsel patients before and during peptide anti-cancer immunotherapy. The present paper summarizes the most relevant altered HLA class I phenotypes found in human tumor samples, indicates their frequency, and outlines the mechanisms implicated. This review also points out that the natural killer (NK) escape mechanism of HLA class I deficient cancer cells is yet to be defined. Knowledge accumulated to date reveals that HLA class I molecules are an important crossroad in tumor immunology. Human Immunology 61, 65-73 (2000).

Heterogeneous cell populations form an interconnected network that determine their collective output. One example of such a heterogeneous immune population is tumor-infiltrating lymphocytes (TILs), whose output can be measured in terms of its reactivity against tumors. While the degree of reactivity varies considerably between different TILs, ranging from null to a potent response, the underlying network that governs the reactivity is poorly understood. Here, we asked whether one can predict and even control this reactivity. To address this we measured the subpopulation compositions of 91 TILs surgically removed from 27 metastatic melanoma patients. Despite the large number of subpopulations compositions, we were able to computationally extract a simple set of subpopulation-based rules that accurately predict the degree of reactivity. This raised the conjecture of whether one could control reactivity of TILs by manipulating their subpopulation composition. Remarkably, by rationally enriching and depleting selected subsets of subpopulations, we were able to restore anti-tumor reactivity to nonreactive TILs. Altogether, this work describes a general framework for predicting and controlling the output of a cell mixture.

The human B cell survival factor, B cell activation factor (BAFF), and its closely related homologue, a proliferation-inducing ligand (APRIL), modulate B cell functions by binding to three receptors, BAFFR, TACI and BCMA. APRIL binds more strongly to BCMA than to TACI while the opposite is true for BAFF.  In addition, BAFF, but not APRIL, binds to BAFF-R with high affinity.  Both BAFF and APRIL are known to form homotrimers and heterotrimers, which display different affinities for their cognate receptors.  To understand the structural basis underlying the different binding affinities, we solved the crystal structure of the APRIL-BAFF-BAFF heterotrimer, either alone or bound to TACI.  Analysis of these structures and comparative analysis of previously solved structures of BAFF and APRIL in complex with BAFFR, TACI or BCMA revealed that the charged residues of BAFF and APRIL are crucial determinants of receptor binding affinities, conferring homotrimers and heterotrimers with a variety of signaling strength to modulate responses of immune cells.

Indukantha Ghritha (IG) is a polyherbal preparation consisting of 17 plant components widely prescribed by ayurvedic physicians for various ailments. Though it is a known ayurvedic drug, no attempt has been made to scientifically validate its mechanism of action. Preliminary studies in our laboratory showed IG to possess considerable immunomodulatory effects with a Th1 type of immune response. In this regard, we attempted to elucidate its role as an adjuvant to cancer chemotherapy. BALB/c mice were administered IG, for a period of 14 days and parameters such as Hb, total and differential WBC count, bone marrow cellularity, lymphocyte proliferation and function, macrophage phagocytosis and tumor remission were studied. Administration of IG could inhibit tumor development in mice challenged with Dalton's lymphoma ascites. IG-induced leukopoiesis and enhanced median survival time as well as life span in tumor bearing animals. Macrophage phagocytic capacity was also elevated. Flow cytometric analysis of lymphocyte subsets and MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium salt] assay for lymphocyte proliferation, yielded promising results which reinforces its use as an adjuvant to cancer chemotherapy. The polyherbal drug could reverse cyclophosphamide-induced myelosuppression in control tumor bearing animals significantly to values near or above normal levels. These results demonstrate the potential of IG, especially in several immunosuppressed conditions and patients suffering from leukopenia as a consequence of cancer chemotherapy.

Cancer has become a leading cause of death worldwide. To deal with medical images to discover tumors and their types, Authors need a distinct experience in understanding medical images. Authors need machine learning techniques to reach great accuracy and speed to analyse these images to avoid a lack of experience or errors. In this paper, Authors will study a (SVM) of machine learning techniques used to classify brain images. SVM will be used in this paper to analyse brain images and discover Benign Tumor and Malignant tumor by using Matlab software. The results of the experiments conducted showed the accuracy of the system provided for the classification of tumor types (Benign, Malignant) found in medical brain images. Authors will adhere in this research that the images to be classified are limited by the presence of only two types of tumors. In the future, some pre-processing procedures will be added to the brain's medical images prior to the classification process.

A tumor is an abnormal growth of new tissues that can occur in any of the body organs. In recent years, there are
many kinds of tumors in human body like brain tumor, bone tumor, lung tumor, etc. Image processing plays a vital role in
analysis and classification of tumor. Medical image processing is an important field of research as its outcomes are used for the
betterment of health issues. Bone tumors develop when cells within a bone divide uncontrollably, forming a lump or mass of
abnormal tissue. There is a large class of bone tumor types which have different characteristics. There are two types of bone
tumors, Noncancerous (Benign) and Cancerous (Malignant). In our project we can mainly concentrate on image segmentation
for bone image and their classification. In the first module input image was segmented and the features are extracted, in the
second module with the use of Support Vector Machine (SVM) and Artificial Neural Network(ANN) classifiers, the images are
classified as Benign or malignant, and then trained image stored in database . This project proposed a simple and easy method to
detect and classify the bone tumor

Kanserli doku çevresindeki immun sistemi adeta "uyutan" sitokinler salgılayarak kendi üzerinde selektif immunsupresyon sağlar. Peki bu immun tolerans kırılabilir mi? Lenfositlere yapay olarak belli antijenler eklenerek kanserli dokuya karşı bir alerji türetilebilir mi?...
İmmunoterapi Yabancı antijen uygulama işlemi olduğu için verilen monoklonal antikorlar ciddi advers yan etkilere yol açabilir. Kanser tedavisinde immunoterapiyi riskli bulsam da sadece mekanizmaları derlemeye çalıştım. Immunoterapi bence ancak büyük tümor kitlelerinin hızlı bir biçimde yok edilmesinde yardımcı olabilir. Monoklonal antikorlar,uygun durumlarda kullanılmadığında; bir protein grefti olarak,yabancı alerjene karşı immun tepkiler oluşturacaktır, bu da trombozdan ciddi organ iskemik yetmezliklerine kadar korkunç tablolara yol açabilir. Kanser tedavisinde temel rolü immunoterapiye vermek, fizyopatolojik mantığa yani tıbbın felsefesine aykırıdır.

Sel dapat berfungsi dengan baik bila terdapat keseimbangan atau homeostasis. Apapun agen baik internal maupun eksternal yang dapat mengganggu keseimbangan tersebut akan berakibat pada perubahan fungsi sel, yang selanjutnya menjadi jejas sel.Sel dan jaringan mempunyai mekanisme tersendiri untuk beradaptasi terhadap jejas, yang berbeda tergantung penyebab jejas dan jenis sel. Apabila sel gagal beradaptasi, terjadilah jejas sel reversibel. Kematian sel terjadi apabila kerusakan sel tersebut bersifat ireversibel sehingga akan teraktivasi program kematian sel.
Neoplasia atau “pertumbuhan baru” adalah proliferasi sel yang tidak tergantung pada proses fisiologis apapun dari sel. Neoplasia disebabkan oleh perubahan genetik sehingga sel mengaktifkan program secara genetik, yang tidak sesuai. Neoplasma yang terbentuk berasal dari proliferasi klonal sel yang mengalami perubahan genetic akibat jejas sel oleh agen lingkungan, yang tidak dapat dieliminasi oleh tubuh.  Neoplasma mempunyai “perangai biologik” yang berbeda-beda tergantung dari karakteristik neoplasma tersebut. Karakteristik inilah yang bermanifestasi dalam berbagai tampilan klinis tertentu. Neoplasma adalah penyakit “multidisiplin”, dimana berbagai ilmu diperlukan untuk menegakkan diagnosis pasti neoplasma, menentukan stadium, prognosis dan penatalaksanaan.

Background: Tumor metabolism is a crucial factor for the carcinogenesis of oral squamous cell carcinoma (OSCC). Methods: Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, PFK-1, LDHA, TKTL1), mitochondrial enzymes (SDHA, SDHB, ATP synthase) were analyzed in normal oral mucosa (n = 5), oral precursor lesions (simple hyperplasia, n = 11; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 42) by immunohistochemistry and real-time polymerase chain reaction (qPCR) analysis in OSCC cell lines. Metabolism-related proteins were correlated with proliferation activity (Ki-67) and apoptotic properties (TUNEL assay) in OSCC. Specificity of antibodies was confirmed by western blotting in cancer cell lines. Results: Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, LDHA, TKTL1), and mitochondrial enzymes (SDHA, SDHB, ATP synthase) were significantly increased in the carcinogenesis of OSCC. Metabolic active regions of OSCC were strongly correlated with proliferating cancer (Ki-67+) cells without detection of apoptosis (TUNEL assay). Conclusions: This study provides the first evidence of the expression of IGF-R1, glycolysis-related proteins GLUT-1, HK 2, PFK-1, LDHA, and TKTL1, as well as mitochondrial enzymes SDHA, SDHB, and ATP synthase in the multi-step carcinogenesis of OSCC. Both, hypoxia-related glucose metabolism and mitochondrial oxidative phosphorylation characteristics are associated with the carcinogenesis of OSCC. Acidosis and OXPHOS may drive a metabolic shift towards the pentose phosphate pathway (PPP). Therefore, inhibition of the PPP, glycolysis, and targeted anti-mitochondrial therapies (ROS generation) by natural compounds or synthetic vitamin derivatives may act as sensitizer for apoptosis in cancer cells mediated by adjuvant therapies in OSCC.

El Hidrógeno Molecular (H2) es considerado el antioxidante mas poderos!
Es la fuente de energía por excelencia para las células que le permite desempeñar por completo todas sus funciones, tales como: desintoxicar, sanar, reparar y regenerar a si misma. Excelente tanto para los atletas profesionales como para personas con todo tipo de padecimientos, y así como para niños o mujeres embarazadas. En Japón son mas de 50 años que se reconoce de forma oficial su efectividad para tratar mas de 170 padecimientos distintos. Por ser el átomo mas pequeño logra penetrar todas las células del cuerpo humano y en tan solo 45 días poder regenerar órganos como el hígado, páncreas, riñones entre otros y lograr recuperar salud y bienestar de forma estable.

Tumor dan kista adalah dua variasi pertumbuhan. Mereka bisa serupa dalam penampilan melainkan mempunyai penyebab berbeda. Untuk menentukan apakah seseorang mempunyai tumor atau kista, dokter bisa menggunakan teknik pencitraan atau mengerjakan biopsi.

Colorectal cancer (CRC) is one of the most common cancer types and represents a major therapeutic challenge. Although initial events in colorectal carcinogenesis are relatively well characterized and treatment for early-stage disease has significantly improved over the last decades, the mechanisms underlying metastasis – the main cause of death – remain poorly understood. Correspondingly, no effective therapy is currently available for advanced or metastatic disease. There is increasing evidence that colorectal cancer is hierarchically organized and sustained by cancer stem cells, in concert with various stromal cell types. Here, we review the interplay between cancer stem cells and their microenvironment in promoting metas-tasis and discuss recent insights relating to both patient prognosis and novel targeted treatment strategies. A better understanding of these topics may aid the prevention or reduction of metastatic burden.

Fetal antigens are allogeneic to the mother's immune system and should theoretically elicit an immune response. The fact that this does not occur and that the fetus thrives for so long in the mother without undergoing rejection by her immune system is a scientific mystery. There are five main theories that could explain the fetus's success in evading the mother's immune system. These are the mother's overall immune suppressed state, maternal tolerance to fetal antigens, down-regulation of fetal antigens, the presence of a barrier between maternal immunity and the fetus, and local immune suppression at the site of the placenta. None of these mechanisms can fully explain this phenomenon despite the varying degrees of evidence in support of each. The last mechanism (local immune suppression) seems to be the most plausible one according to current thinking. The actual explanation of this paradox may well lie in a combination of several different factors rather than a single account. K Ke ey y w wo or rd ds s: : immune system, fetus, pregnancy.

. Без бумажки ты никто. Без нее нет к тебе никакого доверия. Нечто подобное есть и у клеток нашего организма. На поверхность клеток нашего организма высовывается часть белка CD47 и своим появлением предъявляет право клетки на существование в нашем организме. Если такого «документа» нет или он утерян клетку сожрут стражи порядка – клетки называемые макрофагами.

Radiotherapy and chemotherapy are two famous modalities in tumor-targeted therapy that lead to systemic and local toxicities for normal tissues. Moreover, several studies have confirmed that exposure of the tumor to radiation or chemotherapy drugs stimulate some signaling pathways in the tumor microenviron-ment (TME), leading to resistance of cancer cells to apoptosis, as well as promoting angiogenesis and tumor growth. Nuclear factor kappa B (NF-κB) plays a central role in the regulation of inflammatory responses in both normal tissues and tumors via the release of several cytokines, regulation of prostaglandins, reduction/oxidation (redox) reactions, angiogenesis, and cell death. Upregulation of NF-κB in normal tissues causes an appearance of inflammatory reactions and oxidative stress, whereas it regulates angiogenesis and suppresses apoptosis, leading to resistance to subsequent doses of radiation or chemotherapy. Selective inhibition of NF-κB in experimental studies has shown promising results for tumor sensitization via apoptosis induction, inhibition of angiogenesis, and increasing delay of tumor growth. The use of some agents for NF-κB inhibition has been shown to alleviate radiation/chemotherapy toxicities in normal cells/ tissues. In this current review, we explained the pivotal role of NF-κB in both normal tissue toxicity and tumor resistance. We also discussed the promising strategies for overcoming these problems with regard to chemotherapy and radiotherapy.

It has been indicated that beta glucan is potential for anticancer due to its activity as immunomodulator. The aim of this research was to study the antitumor activity of oyster mushroom's beta glucan in female rats induced with 7,12 Dimethylbenz(a)anthracene (DMBA) as cancer promotor. Experimental rats were divided into four groups which consist of control group, DMBA group and beta glucan-treated groups (with two different doses of 0.25 g.kg-1 and 1 g.kg-1). Inhibition of carcinogenesis were demonstrated in beta glucan-treated group which showed lower case of tumor incidence than DMBA group. Total volume and numbers of tumor nodules in beta glucan-treated group were lower than DMBA group. Analysis of histopathology of tumor nodules showed that beta glucan-treated group had a lower score than DMBA group indicating less severity of tumor. In conclusion, beta glucan from oyster mushroom has antitumor activity on DMBA-induced breast cancer in vivo.

It is estimated that more than half of cancer patients undergo radiotherapy during the course of their treatment. Despite its beneficial therapeutic effects on tumor cells, exposure to high doses of ionizing radiation (IR) is associated with several side effects. Although improvements in radiotherapy techniques and instruments could reduce these side effects, there are still important concerns for cancer patients. For several years, scientists have been trying to modulate tumor and normal tissue responses to IR, leading to an increase in therapeutic ratio. So far, several types of radioprotectors and radiosensitizers have been investigated in experimental studies. However, high toxicity of chemical sensitizers or possible tumor protection by radioprotectors creates a doubt for their clinical applications. On the other hand, the protective effects of these radioprotectors or sensitizer effects of radiosensitizers may limit some type of cancers. Hence, the development of some radioprotectors without any protective effect on tumor cells or low toxic radiosensitizers can help improve therapeutic ratio with less side effects. Melatonin as a natural body hormone is a potent antioxidant and anti-inflammatory agent that shows some anti-cancer properties. It is able to neutralize different types of free radicals produced by IR or pro-oxidant enzymes which are activated following exposure to IR and plays a key role in the protection of normal tissues. In addition, melatonin has shown the ability to inhibit long-term changes in inflammatory responses at different levels, thereby ameliorating late side effects of radiotherapy. Fortunately, in contrast to classic antioxidants, some in vitro studies have revealed that melatonin has a potent anti-tumor activity when used alongside irradiation. However, the mechanisms of its radiosensitive effect remain to be elucidated. Studies suggested that the activation of pro-apoptosis gene, such as p53, changes in the metabolism of tumor cells, suppression of DNA repair responses as well as changes in biosynthesis of estrogen in breast cancer cells are involved in this process. In this review, we describe the molecular mechanisms for radioprotection and radiosensitizer effects of melatonin. Furthermore, some other proposed mechanisms that may be involved are presented.

The hypothesis of immunologic surveillance of neoplasia is predicated on the theory that the immune system is capable of discriminating self from foreign antigens, and that tumor-specific antigens are regarded by the immune system as nonself. We propose here an alternate view, that the immune system has evolved to detect danger by employing 'professional' antigen-presenting cells as sentinels of tissue distress. In this model, cancers do not appear dangerous to the immune system, so that the default response of T cells to tumors is to be turned off. We discuss the implications for immunotherapy of malignancy.

Secondary immunodeficiency’s, previously presented in immunocompetent individuals. The lack of primary or secondary response to the presence of a foreign antigen, in the case of infections is a sentinel data in the diagnosis of immunodeficiency (can be primary or secondary), in the case of a self antigen may generate the presence of Cancer. Cancer has shown an increase in the prevalence and incidence globally. Most current medical treatments in cancer are focused primarily on immunomodulatory actions (immunosuppression / immune stimulation or both). Knowledge of key concepts from the perspective of innate andacquired immunity lead to cancer development, engaging immune surveillance and escape mechanisms of this that contribute to better understand the origin, behavior and treatment of neoplasm’s. These treatments can cause immunological disorders such as allergy, anaphylaxis

Purpose

Cancer stem cells (CSCs) are highly tumorigenic cell types that reside within specific areas of tumor microenvironment (TME), and are endowed with self-renewal and resistance properties. Here, we aimed to discuss mechanisms involved in hypoxia-derived CSC resistance and targeting for effective cancer therapy.

Results

Preferential localization within hypoxic niches would help CSCs develop adaptive mechanisms, mediated through the modification of responses to various stressors and, as a result, show a more aggressive behavior.

Conclusion

Hypoxia, in fact, serves as a multi-tasking strategy to nurture CSCs with this adaptive capacity, complexing targeted therapies.

Regulatory T cells (Tregs) represent a low number of T‐cell population under normal conditions, and they play key roles for maintaining immune system in homeostasis. The number of these cells is extensively increased in nearly all cancers, which is for dampening responses from immune system against cancer cells, metastasis, tumor recurrence, and treatment resistance. The interesting point is that apoptotic Tregs are stronger than their live counterparts for suppressing responses from immune system. Tregs within the tumor microenvironment have extensive positive cross‐talks with other immunosuppressive cells including cancer‐associated fibroblasts, cancer cells, macrophage type 2 cells, and myeloid‐derived suppressor cells, and they have negative interactions with immunostimulatory cells including cytotoxic T lymphocytes (CTL) and natural killer cells. A wide variety of markers are expressed in Tregs, among them forkhead box P3 (FOXP3) is the most specific marker and the master regulator of these cells. Multiple signals are activated by Tregs including transforming growth factor‐β, signal transducer and activator of transcription, and mTORC1. Treg reprogramming from an immunosuppressive to immunostimulatory proinflammatory phenotype is critical for increasing the efficacy of immunotherapy. This would be applicable through selective suppression of tumor‐bearing receptors in Tregs, including FOXP3, programmed death‐1, T‐cell immunoglobulin mucin‐3, and CTL‐associated antigen‐4, among others. Intratumoral Tregs can also be targeted by increasing the ratio for CTL/Treg.

Mesenchymal stem cells (MSCs), a non-hematopoietic stem cell population first discovered in bone marrow, are multipotent cells capable of differentiating into mature cells of several mesenchymal tissues, such as fat and bone. As common progenitor cells of adipocytes and osteoblasts, MSCs are delicately balanced for their differentiation commitment. Numerous in vitro investigations have demonstrated that fat-induction factors inhibit osteogenesis, and, conversely, bone-induction factors hinder adipogenesis. In fact, a variety of external cues contribute to the delicate balance of adipo-osteogenic differentiation of MSCs, including chemical, physical, and biological factors. These factors trigger different signaling pathways and activate various transcription factors that guide MSCs to commit to either lineage. The dysregulation of the adipo-osteogenic balance has been linked to several pathophysiologic processes, such as aging, obesity, osteopenia, osteopetrosis, and osteoporosis. Thus, the regulation of MSC differentiation has increasingly attracted great attention in recent years. Here, we review external factors and their signaling processes dictating the reciprocal regulation between adipocytes and osteoblasts during MSC differentiation and the ultimate control of the adipo-osteogenic balance.

Low-dose metronomic (LDM) chemotherapy was developed to overcome resistance to standard, maximum tolerated dose (MTD) chemotherapy by shifting the primary treatment target from the highly adaptive tumor cells to diploid endothelial cells. As such, LDM chemotherapy exerts potent antiangiogenic effects. However, it became rapidly apparent that LDM chemotherapy is subject to resistance on its own, albeit by distinct mechanisms compared to MTD chemother-apy. To address the lack of detailed knowledge on the mechanisms of resistance to LDM chemotherapy, we decided to analyze the characteristics of prostate and breast cancer models with stable acquired resistance to LDM cyclophosphamide (CPA). Whereas our studies suggest that compensatory angiogenic activity does not account for such resistance in a major way, we identified low autophagic activity of tumor cells to be associated with resistance to LDM CPA. In addition, auto-phagy inhibition by using chloroquine in the PC-3 human prostate cancer model, or genetically engineered autophagy deficiency in immortalized baby mouse kidney cell tumors reversed the antitumor effects of LDM CPA. These findings contrast with observations from others showing that autophagy inhibition might enhance the antitumor effects of vascular en-dothelial growth factor (VEGF) targeted antiangiogenic therapy. On the other hand, the impact of autophagy modulation in cancer is known to be highly context-dependent. Since a subset of malignancies is expected to have intrinsic autophagy defects, assessing the autophagy status of tumors may become a tool to select patients for VEGF pathway targeted versus LDM antiangiogenic therapy.

Galectins form a family of carbohydrate-binding proteins defined by their affinity for -galactosides containing glycoconjugates. The carbohydrate recognition domain (CRD) is responsible for the specificity of galectins for saccharides. This binding may result in modulated cell proliferation, cell death and cell migration, three processes that are intimately involved in cancer initiation and progression. Galectins can also display protein-protein types of interactions with their binding partners. Certain galectins directly involved in cancer progression seem to be promising targets for the development of novel therapeutic strategies to combat cancer. Indeed, migrating cancer cells resistant to apoptosis still constitute the principal target for the cytotoxic drugs used to treat cancer patients. Reducing the levels of migration in apoptosis-resistant cancer cells can restore certain levels of sensitivity to apoptosis (and so to pro-apoptotic drugs) in restrictedmigration cancer cells. Anti-galectin agents can restrict the levels of migration of several types of cancer cell and should therefore be used in association with cytotoxic drugs to combat metastatic cancer. We provide experimental proof in support of this concept. While the present review focuses on various experimental strategies to impair cancer progression by targeting certain types of galectins, it pays particular attention to glioblastomas, which constitute the ultimate level of malignancy in primary brain tumors. Glioblastomas form the most common type of malignant brain tumor in children and adults, and no glioblastoma patient has been cured to date.

Carcinoembryonic antigen (CEACAM5) is commonly overexpressed in human colon cancer. Several antigenic peptides recognized by cytolytic CD8+ T-cells have been identiWed and used in colon cancer phase-I vaccination clinical trials. The HLA-A*0201-binding CEA 694-702 peptide was recently isolated from acid eluted MHC-I associated peptides from a human colon tumor cell line. However, the immunogenicity of this peptide in humans remains unknown. We found that the peptide CEA 694-702 binds weakly to HLA-A*0201 molecules and is ineVective at inducing speciWc CD8+ T-cell responses in healthy donors. Immunogenic-altered peptide ligands with increased aYnity for HLA-A*0201 were identiWed. Importantly, the elicited cytolytic T lymphocyte (CTL) lines and clones cross-reacted with the wild-type CEA 694-702 peptide. Tumor cells expressing CEA were recognized in a peptide and HLA-A*0201 restricted fashion, but high-CEA expression levels appear to be required for CTL recognition. Finally, CEA-speciWc T-cell precursors could be readily expanded by in vitro stimulation of peripheral blood mononuclear cell (PBMC) from colon cancer patients with altered CEA peptide. However, the CEA-speciWc CD8+ T-cell clones derived from cancer patients revealed low-functional avidity and impaired tumor-cell recognition. Together, using T-cells to demonstrate the processing and presentation of the peptide CEA694-702, we were able to corroborate its presentation by tumor cells. However, the low avidity of the speciWc CTLs generated from cancer patients as well as the high-antigen expression levels required for CTL recognition pose serious concerns for the use of CEA694-702 in cancer immunotherapy.

P 12 (ppm) ND ND Diésel ultra bajo azufre. Diésel. Líquido Clase 3, "líquidos inflamables" 128 PPT 9 (ppm) IPVS 11 (mg/m 3 ) 2 0 0 VER DESCRIPCIÓN DE RIESGOS EN SECCIÓN XIII (PAGINA 7) SEVERO SERIO MODERADO LIGERO MÍNIMO 4 3 2 0 1 GRADO DE RIESGO NFPA 3

The expression of Bt gene in transgenic cotton is impacted by several abiotic factors. The current study was designed to evaluate the effect of temperature on Bt gene expression in selected cotton genotypes under glasshouse condition. A total of 124 genotypes (V-1 to V-124) were cultivated between temperature range 25-30°C. All the genotypes were assessed for the detection of Bt gene(s) by immunostrip assay and PCR analysis that revealed the presence of only Cry1Ac gene, except for five genotypes. Fresh leaf tissues were collected from all genotypes and Cry1Ac gene expression (Bt toxin) was quantified through quantitative ELISA kit at 70 days after sowing. Ten genotypes with the highest Cry1Ac toxin level (1.00-4.17µg/g) were selected and shifted into 4 different glasshouses under the temperature ranges of 25-30°C, 31-35°C, 36-40°C and 41-45°C respectively. Cry1Ac expression level was again quantified after 10 days of varying temperature treatments at 80 days after sowing. Significant reduction in toxin level (P = 0.001) was found under different temperature treatments. The mean toxin level was found to be lowest (1.62µg/g) at the highest temperature range (41-45°C), followed by toxin level (2.01µg/g) at treatment level (36-40 °C). The treatment level (31-35°C) showed higher toxin level (2.50µg/g) as compared to control (25-30°C) (2.29µg/g) and other treatments as well. It can be concluded that mild temperature i.e 31-35°C is the best range for maximum expression Cry1Ac toxin in transgenic cotton genotypes. Moreover, higher temperature above 40°C may have adverse effects on the expression of Cry1Ac toxin in leaf tissue, with resulting decline in Bt toxin level.

Helmut Sies established the concept of oxidative stress in 1985.
However, it took some time to introduce this concept into
pathology, where investigators count on formalin-fixed
paraffin-embedded tissue sections. I sought out antigens for
this purpose based on an oxidative stress-induced rat renal
carcinogenesis model, which revealed that 8-hydroxy-2′-
deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins
are ideal. These two monoclonal antibodies successfully
revealed the involvement of oxidative stress in numerous human diseases, including carcinogenesis and atherosclerosis.
Shigeru Okada established the aforementioned ferric
nitrilotriacetate (Fe-NTA)-induced rat renal carcinogenesis
model, which thus far has answered many questions regarding
the presence of target genes in oxidative stress-induced carcinogenesis and the sites that are susceptible to oxidative stress in the genome. Particularly, the similarity of genomic alterations between Fe-NTA-induced renal cancer and human cancers suggests that excess iron plays a role also inhuman carcinogenesis. Furthermore, excess iron is amajor pathology in asbestosinduced mesothelioma, including chrysotile. Despite an analogy to asbestos, multi-wall carbon nanotubes were distinct in that diameter is another responsible factor for mesothelial carcinogenesis. Recently, non-thermal plasma emerged as a candidate for medical intervention for wounds and cancers via manipulating oxidative stress. Counteracting excess iron is a promising preventive strategy for major diseases.

Cancer associated fibroblasts (CAFs) as the dominant, long-lived and highly plastic cells within the tumor microenvironment (TME) with multi-faceted roles that are endowed with tumor aggressive features. They can instruct and shape the stroma of tumor into being a highly qualified bed for cellular recruitment, differentiation and plasticity in the host tissue or secondary organ/s. In this Review, we have a discussion over CAF reprogramming as a general concept, inducers and outcomes, pursued by suggesting potential strategies to combat this key promoter of tumor.

Head and neck cancer represents a challenging disease. Despite recent treatment advances, which have improved functional outcomes, the long-term survival of head and neck cancer patients has remained unchanged for the past 25 years. One of the goals of adjuvant cancer therapy is to eradicate local regional microscopic and micrometastatic disease with minimal toxicity to surrounding normal cells. In this respect, antigen-specific immunotherapy is an attractive therapeutic approach. With the advances in molecular genetics and fundamental immunology, antigen-specific immunotherapy is being actively explored using DNA, bacterial vector, viral vector, peptide, protein, dendritic cell, and tumor-cell based vaccines. Early phase clinical trials have demonstrated the safety and feasibility of these novel therapies and the emphasis is now shifting towards the development of strategies, which can increase the potency of these vaccines. As the field of immunotherapy matures and as our understanding of the complex interaction between tumor and host develops, we get closer to realizing the potential of immunotherapy as an adjunctive method to control head and neck cancer and improve long-term survival in this patient population.