Dendritic cells (DC) are also an important tool for tumor-antigen-specific immunotherapy of cancer because of their critical role in mounting a specif- ic immune response where their intratumoral and peritumoral density as well as their functional status are correlated with clinical staging ofthe disease and patient’s survival [24-37]. DC originates from hematopoietic stem cells with inthe bone marrow. Under phsiological conditions both myeloid and lymphoid precursors differentiate into immature dendritic cells. In peripheral tissues, upon the up- take of antigen, receiving danger signals or inthe context of inflammation, DC undergo maturation process and migrate to the secondary lymphoid or- gans . This maturation process is characterized by increased surface expressing of antigen present- ing surface molecules like major histocompatibility complexes (MHC class I interacts with CD8+ cells whereas MHC class II interacts with CD4+ cells) and co-stimulatory molecules such as CD-54, CD- 58, CD-83, CD-80 and CD-86 and secrete several pro-inflammatory cytokines (IL-2,IL-4,IL-6, IL-12, TNF-α etc.) [19,38]. (Figure 1) As a result of this maturation process, DC are well equipped to acti- vate naive T cells; CD 8+ T cells differentiate into cy- totoxic T cells (CTL) while CD+4 T cells differentiate into T helper-1 (Th1) or T helper-2 cells (Th2) which interact with macrophages and B cells, respective- ly, thus providing a link between the adaptive and innate immune system inthe secondary lymphoid organs [19,37]. A Th1 immune response and also CTL activation are the goal of utilizing DC as a can- cer vaccine in order to eliminate tumor . DC are not just regulators ofthe immune response, but also maintenance ofthe immune tolerance inthe thymus and secondary lymphoid organs. DC present self antigen (Ag) to develop immune cell and induce de- letion of autoreactive T cells result in self tolerance depending on the status ofthe immune system: steady state versus infection. This situation very im- portant for DC-based anti-tumor immunotherapies to control DC differentiation to prevent undesirable effects of vaccination such as tolerance induction by tolerogenic DC . Moreover, immune evasion of tumor cells by down-regulation of surface or in- tracellular molecules are also limiting factors for the efficiency ofthe DC-based vaccination in tumor pa- tients. The other limiting factors are the secretion of soluble immunosuppressive cytokines by tumor cells that convert immature into tolerogenic DC and presence of naturally occurring, antigen-specific regulatory T cells. However, DC-based vaccination
In order to utilize genes and proteins as biomarkers for disease and/or treatments as for drug responders, more experience and Research & Development inputs are requested. For diagnostic quantification of protein(s) in clinical studies, there are currently no standard guidelines from the Food and Drug Administration (FDA) or European Medicines Agency (EMEA) that need to be met for approval. However, there are on-going projects concern- ing such biomarkers development between the FDA, academics projects and pharmaceutical industry that are investigating standardization procedures for future utilization. A guideline for industry has recently been introduced (http://www.fda.gov/ downloads/RegulatoryInformation/Guidances/ucm126957.pdf). The initial step of a SRM assay development usually relates to apply an in silico step, where a selection of suitable peptides from the proteins are made, followed by BLAST searching in protein database, where identified peptides from the proteins can verify the utility of target peptides identified as candidates. Precursors and m/z ofthe peptide products are the keys to the assay development. Recently, a rapid assay development with SRM-MS instrumentations was presented . In this respect, peptides libraries used as standards, are the most valuable tools in order to funnel the large number of peptide candidates inthein silico processing step that make judgments ofthe most useful target peptide candidates for the assay [44,45].
ABSTRACT – Introduction: The appearance of pigmented lesions in scars ofmalignantmelanoma is a finding that worries dermatologists/dermatopathologists, because they are faced with the possibility of persistence/recurrence ofmalignantmelanoma. Case reports: We present three cases of patients with melanocytic pigmentation in scars of ma- lignant melanoma and discuss the clinical and histological aspects of these. In all cases, we observed macules similar to lentigo spots, but histologically we observed three different patterns: lentiginous epidermal hyperplasia, lentiginous hyperplasia of melanocytes and malignantmelanomain situ. Discussion: There are three types of pigmentation, which may arise inthe scar ofmalignantmelanoma: lentigo type lesions, pigmented streaks and diffuse pigmentation. His- tologically, three patterns of melanocytic pigmentation in scars ofmalignantmelanoma, are described: lentiginous epidermal hyperplasia, lentiginous hyperplasia of melanocytes and persistence/ recurrence ofmalignantmelanoma. The scar appears to be responsible for pigmentation by a process of induction acting on epidermal melanocytes.
In general, brain metastatic tumors are resistant to chemotherapy and even some newly emerged targeted therapeutic regimens. The blood-brain barrier (BBB) is known as the major obstacle for delivering drugs to the site of tumor cells inside the brain, due to low drug penetration (18). Therapeutic approaches are being selected based on the type of primary cancer, the number and location ofthe metastatic lesions as well as the stage of cancer. Current standard treatment for patients with brain metastasis is surgical resection followed by radiotherapy, and sometimes chemotherapy. These treatments may decrease the chance of recurrences of brain metastasis, and can increase the patient's quality of life (23). Precise considerations must be applied before choosing a proper treatment. A convenient selection of pharmacological agents can help patients with certain hindering symptoms. However, an unjustified choice oftreatment could lead to a reduction inthe patient's quality of life. In general, the life expectancy for patients with brain metastasis is poor, around 6 months regardless oftreatment (22).
Introduction: Local progression of papillary thyroid carcinoma (PTC) after failure of standard therapies may cause pain, ulceration, and bleeding. As patients are fully aware ofthe tumor growth, they might suffer high grade anxiety. Electrochemotherapy (ECT) is a new local pallia- tive treatment for skin metastases ofmalignantmelanoma or other tumors, including squamous head e neck cancer patients.
trunk in polypoid, limbs in verrucous, and subungual in chondroid melanoma. We identified ulceration in 73% of poly- poid, in 60% of verrucous and 50% of amelanotic melanomas. A higher mortality rate was documented in mixed variant (polypoid/animal-type), desmoplastic, polypoid and animal-type. Conclusions: The recognition of these variants is im- portant, not only by the clinical and histopathological challenge inthe differential diagnosis with other skin tumors, but also because ofthe possible implication of some of these variants, with peculiar biological behavior, inthe prognosis.
We report a case of primary acquired corneal melanosis without atypia associated with corneal haze in a patient with a history of limbal malignantmelanoma and the effect of mitomycin-C. A 75-year-old woman with a history of limbal malignantmelanoma presented with loss of vision in right eye. Corneal examination showed a patchy melanotic pigmentation with a central haze. Topical mitomycin-C im- proved visual acuity and corneal haze. However, the pigmented lesions persisted, and they were removed with alcohol corneal epitheliectomy. Histopathological examination demonstrated primary acquired melanosis without atypia. The lesions were successfully removed, and there were no recurrences during the follow-up period of 36 months. The association of conjunctival and corneal melanosis without atypia is a rare condition. In addition, co-existence of central corneal haze and melanosis may decrease visual acuity. Topical mitomycin-C and alcohol corneal epitheliectomy can be useful treatments in this condition.
The primary malignantmelanomaofthe uterine cervix is rare, usually diagnosed at an advanced stage and with poor prognosis. The diagnosis is made through histological evaluation and confirmed by special staining procedures. Radical surgery has been used and advocated. However in its advanced stages chemotherapy, immunotherapy or radiotherapy can be employed. A case of a patient with malignantmelanomaofthe uterine cervix, Stage IIIb, is presented in addition to a clinical and pathological discussion.
The macroscopic characteristics usually suggest the diagnosis at physical examination. Malignantmelanoma is usually pigmented but may be devoid of pigment (amelanotic melanoma) and can contain both pigmented and nonpigmented lesions in a zosteriform pattern , with ulceration and necrosis being usually present.
jeni su i analizirani iz bolničkih baza šest referentnih onkološ- kih centara u Srbiji, na osnovu strukturisane ankete, sa foku- som na metastatski melanom (inoperabilni stadijum IIIC i IV). Rezultati. Ukupno je lečeno 986 (79–315 u različitim centrima) bolesnika, od čega je 320 (32,45%) bilo novodijag- nostikovanih. Bilo je 317 bolesnika u stadijumu inoperabilnog melanoma IIIC/IV, 77/317 (24,29%) starosti < 50 godina. U vreme postavljanja dijagnoze 47,3% bolesnika bili su < 60 godina starosti (24,2% < 40 godina, 38% 40–60 godina, 46% > 60 godina). Kod 12,5% bolesnika dijagnoza je postavljena u stadijumu III, a kod 4,5% u stadijumu IV bolesti. Najčešći kliničkopatološki tip bio je površnošireći (50–66%) i nodular- ni melanom (23,5–50%). Osim regionalnih i udaljenih metas- taza limfnih čvorova, najčešće zahvaćeni organi u IV stadiju- mu bolesti bili su; udaljene metastaze kože i mekih tkiva (12– 55%), pluća (19–55,5%), jetra (10–60%) i kosti (3–10%). Prva linija terapije u inoperabilnom stadijumu III i stadijumu IV metastatskog melanoma bio je dakarbazin (dimetril-triazeno-
Results: Ofthe 397 melanomas included, 52.6% were of feminine sex and 47.4% ofthe masculine. Of these melano- mas only 9.3% were histologically associated with nevus, with discrete predominance of cases inthe feminine sex (54%, p=0,033). Inthe group ofthe MAN the average of ages was slightly inferior (56,5 vs 59,3 years, p=0,577). The trunk was the preferential localization of all the melanomas (42.1%, p=0,005). Histologically the superficial spreading sub- type was more frequently associated with MAN. The MAN were thinner than the MN (1,42 versus 2,13 mm, p=0,030), specially inthe feminine sex (0,99mm, p=0,031). The Breslow tumor thickness and the presence of ulceration had a significant statistical correlation with the metastatic spread and the mortality by melanoma.
household, the program caused an increase of more than 11 percentage points inthe probability of attending school. One possible reason for this increase inthe estimated impact is the fact that his/her family is only receiving any transfers from the Bolsa Familia program because he/she is attending school. The fear of losing access to the program, which means that it may take time to come back to it in case of harder times ahead, may stimulate parents to monitor their kids’ school attendance more strongly. When these two features were combined — i.e. male youngsters who were the youngest child — the probability of attending school increased by 16.2 percentage points and it is statistically significant at the 1 per cent level.
From the analysis, it was found that lands were acquired majorly by inheritance and the resultant effect of this is the fragmentation of land during the acquisition and sharing of either family or community lands. The evident of this was seen on the sizes ofthe land cultivated by both the male and female farmers of which majority of both sexes cultivate a small farm size of 0.1-2.0ha of land with just a few who cultivate a reasonable land size this can also be seen on the number of bag of both garri and fufu produced yearly. However this Land holding in hectares favors more males than females inthe study area and females had better production in cassava than male.
Based on the objectives to be achieved and problems that have been formulated, the method used is juridical- sociological. The juridical approach is intended to explore and study the legislation as a basis for a research, while the sociological approach is intended to explore the factors and impacts incurred from the occurrence of border-area dispute and solution by the government. The specifications of this research are normative law called also as doctrinal research. A site was chosen by researcher to conduct a research is a government agency that includes the Navy (Department of Hydro-Oceanographic) related to the sea boundaries ofthe Republic of Indonesia and neighboring countries, local governments, especially inthe leading islands border to the Republic of Indonesia related to culture, security, politics and thinking about the area/island they occupy, as a part ofthe Unitary ofthe Republic of Indonesia. The population is all research objects to be researched. In this research, the population is Navy and the relevant agencies involved inthe security of sea area. The samples were chosen to be a material of research is the bearer ofthe security function in marine areas through the random system and interviews with relevant parties, such as Bakorkamla and community.