Prediction of recurrence in incompletely excised basal cell carcinoma

This 5-year prospective study evaluated histologic criteria as predictors of tumor recurrence for the individual with a "positive-margin" basal cell carcinoma. The results demonstrated that 93 percent of patients with greater than 75 percent of their tumor cords containing irregularities in in the peripheral palisade had tumor recurrence, while no patient with less than 25 percent of their tumor cords containing irregularities in the peripheral palisade developed a recurrence in 5 years of follow-up. After statistical analysis for the other histologic variables, the presence of greater than 75 percent irregularities in the peripheral palisade conferred a 39-fold increased risk of tumor recurrence, significant at the p much less than 0.001 level. For the patient in the intermediate group (25 to 75 percent irregularities in the peripheral palisade), the presence of a weak host response (absent to minimal infiltration of small lymphocytes) increased the risk of tumor recurrence fourfold, with this effect being significant at the p less than 0.05 level. The presence of tumor ulceration conferred a 2.8-fold increased risk for tumor recurrence, significant at the p less than 0.01 level, while the presence of squamous differentiation conferred no increased risk. This study may provide a valid basis for predicting tumor recurrence in the individual with a positive-margin basal cell carcinoma.     

Simultaneous flow cytometric detection of nuclear DNA and tumor-associated antigens in lung cancers

Flow cytometric (FCM) determinations of DNA index were found to be insufficient to distinguish the presence of tumor cells from normal ones in neoplastic tissues obtained from 29 patients with lung cancer. Therefore, the DNA and tumor-associated antigen (TAA) contents of cultured human lung cancer cells were simultaneously analyzed using FCM to assess whether this dual technique would help in distinguishing tumor cells from normal ones. For the study, cells from PC-10 (a squamous cell carcinoma line), PC-3 (an adenocarcinoma line) and PC-6 (a small cell carcinoma line) were mixed with normal peripheral lymphocytes. The TAAs studied were carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA) and neuron-specific enolase (NSE). The alcohol-fixed cells were treated with the respective primary TAA, followed by fluorescein-isothiocyanate-conjugated secondary antibody; the cellular DNA was then stained using propidium iodide. Red and green fluorescences were measured simultaneously by FCM. The results showed CEA mainly in PC-3 cells, SCC in PC-10 cells and NSE in PC-6 cells; thus, each cell type had a relatively specific TAA. DNA content and cell size analyses differentiated neoplastic cells from normal lymphocytes for PC-3 and PC-10 cells, but not for PC-6 cells. Simultaneous FCM analyses of DNA and the TAA specific for the individual cell type made it possible to distinguish all tumor cell types from normal lymphocytes.     

Basal cell adenocarcinoma of the salivary gland: report of a case with morphology on fine needle aspiration cytology

BACKGROUND: Basal cell adenocarcinoma of the parotid is rare and prone to recur. CASE: A 54-year-old woman had a history of afacial mass 12 years earlier that had been excised and was diagnosed as low grade adenocarcinoma of the parotid. Over the years, the patient had multiple local and lymph node recurrences. Histology of the excised local recurrent tumor showed basal cell adenocarcinoma, and FNAC of a separate recurrent nodule was performed. The aspirate showed moderate cellularity of basaloid cells with mildly pleomorphic nuclei, small nucleoli and occasional mitotic figures. The cells were mostly single, but some formed clusters with a rosettelike pattern of tumor cells surrounding central eosinophilic globules. A second, less prominent population of smaller cells with dark-staining nuclei was also noted. The differential diagnosis included adenoid cystic carcinoma, polymorphous low grade adenocarcinoma, and basal cell and pleomorphic adenoma. CONCLUSION: The cytologic features of basal cell adenocarcinoma are not distinctive, but the presence of two cell populations with moderate pleomorphism and a rosettelike pattern with central, eosinophilic globules may assist with its differentiation from other salivary gland neoplasms.     

人胃癌组织中乙酰肝素酶和S-100蛋白的表达及其意义

目的:探讨乙酰肝素酶和S-100蛋白在人胃癌组织中的表达及其意义。方法:根据胃癌的病理大体分型将40例胃癌组织分为早期组和晚期组。其中,早期组同时未伴有淋巴结转移,晚期组伴有淋巴结转移。采用光镜、透射电镜、原位杂交和免疫组化方法对这两组胃癌组织的超微结构,乙酰肝素酶和S-100蛋白表达进行检测。结果:早期组乙酰肝素酶阳性表达细胞较少,晚期组阳性细胞较多,二者数密度和面密度比较。具有统计学意义(P<0.01);早期组S-100蛋白阳性表达细胞较晚期组多,二者比较,具有统计学意义(P<0.01);电镜观察可见:在胃癌早期,淋巴细胞和树突状细胞浸润较多,树突状细胞突起与淋巴细胞相接触,基底膜基本完整。晚期,基底膜几乎消失。淋巴细胞和树突状细胞浸润较少,癌细胞穿基膜明显。结论:乙酰肝素酶和S-100蛋白的表达程度可作为判定胃癌的侵袭和转移的指标,对其预后的判断具有参考价值。     

Stimulated γδ T cells increase the in vivo efficacy of trastuzumab in HER-2+ breast cancer

One fourth of women with HER-2(+) metastatic breast carcinoma are treated with a combination regimen with trastuzumab, but the frequent resistance to this Ab requires definition of new means to improve its bioactivity. The mechanisms of action of trastuzumab involve several pathways including Ab-dependent cellular cytotoxicity. Because human γδ T lymphocytes mediate Ab-dependent cellular cytotoxicity and can be activated further by phosphoantigens, these cells are prone to improve the efficacy of Abs, as recently demonstrated for CD20(+) B cell lymphomas. Whether this concept applies as well with carcinomas remained to be demonstrated in vivo, however. In this study, we asked whether a combination of trastuzumab and phosphoantigen-stimulated γδ lymphocytes increases the efficacy of trastuzumab against HER-2(+) breast carcinoma cell lines in vivo. We report that repeated infusions of this combination had a better efficacy than that of trastuzumab alone against HER-2(+) mammary carcinoma xenografts in mice. In these models, reduction of tumor growth was observed together with trastuzumab opsonization of HER-2(+) cells and tumor infiltration by γδ lymphocytes. In addition in humans, the mammary carcinomas of 27 of 30 patients showed significant γδ T cell infiltrates. Altogether, these findings indicate that combination of trastuzumab and stimulated γδ cells represents a new strategy to improve the efficacy of Herceptin (trastuzumab) in HER-2(+) breast cancer.     

Impairment of lymphocyte locomotion in the tumor microenvironment and the effect of systemic immunotherapy with liposome-encapsulated myramyl-tripeptide-phosphatidylethanolamine

  The ability of the lymphocytes to move through the interstitium is obligatory to the immune response. We previously showed that tumor-infiltrating lymphocytes (TIL) from human melanoma and renal cell carcinoma demonstrate a dramatic decrease in their spontaneous locomotion through three-dimensional collagen gel when compared with peripheral blood lymphocytes (PBL) and lymph node lymphocytes. To determine if this decrease is caused by contact with tumor cells, or mediated through certain diffusible factors, we examined the effects of autologous tumor cells on the locomotion of PBL in a model system where tumor cells were separated from lymphocytes by a 3-mm layer of gelled collagen. After 21–22 h incubation in chamber slides, locomotion distances were assessed in the presence and absence of tumor and normal cells. In the presence of tumor cells, PBL from 14 of 18 patients displayed substantial (466.5 ±2.7 μm compared to control 568.9 ± 10.9 μm, P<0.001) loss of motility. Inhibition was more prominent in melanoma patients than in renal cell carcinoma patients. Thus the impaired locomotion previously observed in TIL was at least partially due to the presence of tumor. The locomotion of TIL was restored in four of five melanoma patients treated with liposome-encapsulated muramyl-tripeptide-phosphatidylethanolamine (L-MTP-PE). Furthermore, in six of seven examined L-MTP-PE-treated patients, an increase in intrinsic PBL locomotion during the first month of the therapy was observed. These results suggest that the environment of the tumor is not conducive to locomotion of advancing lymphocytes and the therapeutic intervention may ameliorate the loss of lymphocytic infiltration. Received: 16 May 1994 / Accepted: 26 August 1994     

Immune mechanisms in the pathogenesis of idiopathic inflammatory myopathies

Idiopathic inflammatory myopathies (IIMs), comprising polymyositis, dermatomyositis, and inclusion-body myositis, are characterized by inflammatory cell infiltrates in skeletal muscle tissue, muscle weakness, and muscle fatigue. The cellular infiltrates often consist of T lymphocytes and macrophages but also, in some cases, B lymphocytes. Emerging data have led to improved phenotypic characterization of the inflammatory cells, including their effector molecules, in skeletal muscle, peripheral blood, and other organs that are frequently involved, such as skin and lungs. In this review we summarize the latest findings concerning the role of T lymphocytes, B lymphocytes, dendritic cells, and other antigen-presenting cells in the pathophysiology of IIMs.     

Characterization of tumor-associated lymphocytes in a series of mouse mammary tumor lines with differing biological properties

Tumor-associated lymphocytes were isolated by isokinetic gradient separation from five related mouse mammary tumor lines with different immunological and growth characteristics. Although considerable variation in recovery rates was seen from experiment to experiment, the five tumor types were found to have reproducible and characteristic patterns of T lymphocyte subpopulations, as detected by cytotoxicity assay using monoclonal antisera to Thy-1, Lyt-1, and Lyt-2 antigens. Tumors of line 168, which are weakly immunogenic at best, had the lowest numbers of recovered ALS+, Thy1+ lymphocytes (12% and 9%, respectively), in contrast to immunogenic lines (mean 38% and 26%, respectively). Line 68H tumors, which grow after prolonged latency periods and also produce tumor cell variants in vivo, were unique in that the numbers of recovered Lyt 1+ lymphocytes exceeded the number of Lyt 2+ lymphocytes, whereas these two T cell subpopulations were either equal or Lyt 2+ cells predominated in the other faster growing, non-variant-producing tumors. No differences in T lymphocyte distribution were associated with the presence or absence of metastatic behavior. These results indicate that distinctive lymphocyte infiltrates may be characteristic of tumors with distinct biological differences.     

Inducible nitric oxide synthase-mediated proliferation of a T lymphoma cell line.

Nitric oxide (NO)-derived from T lymphocytes in an autocrine fashion can modulate events in the cell. However, the exact role of NO on the control of lymphocyte growth is controversial since both stimulation and inhibition have been demonstrated. Nitric oxide synthase (NOS) activity in normal and tumor T lymphocyte proliferation was studied here. Resting normal T lymphocytes displayed low levels of NOS activity that were slightly increased upon mitogenic stimulation. In contrast, BW5147 T lymphoma cells displayed higher basal levels than normal T lymphocytes that were significantly augmented when induced to proliferate. This activity was slightly modified in the presence of the calcium chelator EGTA and was blocked by competitive and irreversible NOS inhibitors, as well as by selective blockers of iNOS. Furthermore, tumor but not normal cell proliferation was impaired by NOS and iNOS blockers, while a calcium blocker only affected normal cell growth. iNOS expression, both at the protein and at the mRNA levels, was demonstrated on growing BW5147 cells but not on arrested tumor or normal lymphocytes. The contribution of iNOS to sustained proliferation of tumor cells is discussed.     

Assessment of the number of local cytotoxic T lymphocytes required for degradation of micrometer-size tumor spheroids

Adoptive immunotherapy with human cytotoxic T lymphocytes (CTL) is a promising cancer treatment. Previously we showed that human CTLs against various types of tumors can be efficiently produced by coculturing peripheral blood cells with target cells. The aims of this study were to simulate the interaction of CTLs and micrometer-size tumor tissues in vitro and to assess the required number of CTLs at local tumor sites for degradation of a tumor. Allogeneic CTLs against a human transitional cell carcinoma cell line and autologous CTLs against a renal cell carcinoma cell derived from a surgical specimen were generated. The cytotoxic activities of CTLs against tumor cells in monolayer culture and tumor spheroids formed in U-bottom 96-well culture plates were assessed. Both allogeneic and autologous CTLs showed greater destructive activity than lymphokine activated killer (LAK) cells against target tumor spheroids. CTLs inoculated at E/T ratios of 0.1 to 1 coexisted with the tumor spheroid for 5 to 6 days and then increased in number with apparently lethal activity against the tumor spheroid. In contrast to CTLs, the increase in LAK cell numbers was scarcely observed, and the proliferated LAK cells did not show cytotoxicity against the tumor spheroid. These observations suggest that, when a small number of CTLs reach a local tumor site, they can destroy micrometer-size tumors after considerable local proliferation. This revised version was published online in August 2006 with corrections to the Cover Date.     

A granulocytosis-inducing tumor inhibits the production of B lymphocytes in murine bone marrow

Mice bearing a transplantable CE mammary carcinoma have been shown to have greatly augmented rates of neutrophil production coupled with a marked diminution of bone marrow lymphocytes. The objective of the present study was to test whether the loss of lymphocytes, and especially of B cells, from the bone marrow and spleen of tumor-bearing animals was due to a reduced rate of cell production and if so, at what level this response was regulated. A modified 3H-TdR pulse and chase analysis was used to assess the rates of production of small lymphocytes and B cells (stained for c mu and s mu) at weekly intervals after CE tumor transplantation. 3H-TdR was infused continuously for 24 hr, and radioautographs were prepared of bone marrow and spleen cells 0, 24, and 48 hr after termination of the infusion. Pre-B cells (c mu+s mu-) essentially disappeared from the femoral bone marrow by the end of 1 wk of tumor growth, followed by a great reduction in the number of c mu+s mu+ cells in the marrow and s mu + cells in the spleen. Although pre-B cells appeared in the peripheral marrow (caudal vertebrae, metatarsal bones) and spleen of tumor-bearing mice, these cells could not compensate for the continued decrease in the numbers of more mature B cells. In normal mice, during the 48-hr chase period, newly formed, 3H-TdR-labeled, small lymphocytes and s mu+ cells continued to emerge from the prelabeled precursor compartment at a steady rate, but after 1 wk of tumor growth, the number of small lymphocytes and s mu+ cells emerging from the precursor compartment fell steadily during the 48-hr chase period. During the second and third weeks of tumor growth, a steady state appears to have been reached in B cell production, which was at a level approximately 10 times below that of normal. Because pre-B cells are normally maintained by a less mature precursor population (2), the initial disappearance of c mu+s mu- cells suggests that the CE mammary carcinoma exerts its modulatory influence on primary B cell production by inhibiting or eliminating the cells that eventually feed into the pre-B compartment. The nature of the regulatory factors apparently secreted by the tumor and the more precise identity of the target cells are under investigation.     

Lymphokine activated killer cells

Various subpopulations of human leukocytes may be induced by lymphokines to exert cytotoxic activity. In man major histocompatibility complex non-restricted tumor cell lysis by interleukin-2 (IL-2) induced peripheral blood lymphocytes is attributed mainly to natural killer cells. These T cell receptor negative large granular lymphocytes are called lymphokine activated killer (LAK) cells. In order to explore the potential of LAK cells in tumor therapy, several clinical studies have been conducted, using IL-2 alone or in combination with ex vivo IL-2-activated peripheral blood lymphocytes. Objective responses have reproducibly been achieved only in renal cell carcinoma and malignant melanoma and were associated with considerable toxicity. In view of restricted efficacy and increasing doubts as to whether LAK cells indeed account for the in vivo observed responses, more recent strategies focus on tumor antigen specific cytotoxic T cells or tumor infiltrating lymphocytes. Successful translation of this approach into clinical practice, however, may be dependent on some basic problems of tumor immunology to be solved which were thought to be by-passed by the LAK cell approach.     

Characterization of a human follicular thyroid carcinoma cell line (UCLA RO 82 W-1)

A thyroid tumor cell line has been established from the metastases of a follicular carcinoma in a female patient. Although the primary tumor released thyroglobulin (Tg) into the circulation (greater than 10,000 ng/ml), the uptake of I131 was less than 2%. After 37 replications the doubling time was 4 days and confluency was reached after 7 days from inoculation of 3 x 10(7) cells. This human thyroid tumor cell line has now been growing in culture for several years. An aneuploid chromosomal pattern was observed (62-82 chromosomes). A pair of X chromosomes was present but no Y chromosome was found which is compatible with the female origin of the cell line. EM studies revealed the presence of microvilli. Immunoperoxidase staining using specific anti-human Tg antisera indicated the presence of Tg within the cells. Nude mice developed solid-cystic tumors within 6 months after injection of the cells. The basal release of immunodetectable Tg, as measured in a perifusion system, increased in response to thyroid stimulating hormone (TSH) (P less than 0.025) or TSH combined with theophylline (P less than 0.001). Unusual isoenzyme patterns for galactose-1-phosphate-uridyltransferase (GALT) and phosphoglucomutase1 (PGM1) were detected in the tumor, compared with normal human fibroblasts and blood cells and isoenzyme patterns from the patient's lymphocytes. Because this malignant human thyroid follicular cell line has retained the ability to synthesize Tg it represents a valuable model for the study of human follicular carcinomas.     

First reported case of concurrent sonidegib and radiotherapy for recurrent,advanced basal cell carcinoma

Basal cell carcinoma (BCC ) is the most common human malignancy. Systemic therapy with a sonic hedgehog (SHH) pathway inhibitor plays an important role in the treatment of advanced BCC . Literature on concurrent use of radiation therapy (RT ) with SHH inhibitors has been minimal and has solely been focused on vismodegib. We present a case report of a patient with recurrent basal cell carcinoma involving the high-risk area of the face, who was denied surgery due to comorbidities and difficulty in obtaining complete tumor removal without cosmetic or functional impairment. The patient received combined treatment of fractionated radiation with concurrent sonidegib and had complete clinical response with no significant toxicities. This is the first reported case on the use of concurrent RT with sonidegib for management of recurrent basal cell carcinoma of the head and neck.     

Clonal analysis and in situ characterization of lymphocytes infiltrating human breast carcinomas

Summary T lymphocytes were isolated from tumor biopsies in 13 patients with breast carcinomas. Immunohistology with monoclonal antibodies confirmed the presence of mononuclear cell infiltrates composed primarily of T lymphocytes in all tumors studied. While the proportion of T lymphocytes expressing the T4 or the T8 surface marker varied from tumor to tumor as determined by morphometric analysis, T8+ cells were more numerous than T4+ cells in 8/12 breast tumors studied. Relatively few T cells (<10% in 11/12 tumors) were in an activated state as judged by the surface expression of HLA-DR antigens or the receptor for interleukin-2 (IL-2). In 1 case 20% of the infiltrating mononuclear cells were expressing the IL-2 receptor. The tumor infiltrating lymphocytes (TIL) recovered from 10 tumors were cloned in a microculture system that permits proliferation of nearly 100% of normal peripheral blood T lymphocytes (PBL-T). In contrast to normal and autologous PBL-T, frequencies of proliferating T lymphocyte precursors (PTL-P) were depressed (<0.01) in 7/10 TIL preparations indicating a decreased responsiveness of TIL to phytohemagglutinin at the single-cell level. The frequency of PTL-P was noticeably higher in 2 cases (0.03 and 0.09) and close to normal in 1 case (0.39).A total of 170 clones were expanded in vitro and analyzed for different functional capabilities. Most of these clones expressed the T4+/T8-phenotype (73%) and strikingly 53% of these T4+/T8– clones were cytolytic in a lectin-dependent assay, a functional subset which is uncommon among normal PBL-T. Some clones (10%) lysed allogeneic breast tumor cells (MCF7). Only 15% of the clones displayed natural killer activity. Among the cytolytic clones, 17 of 31 tested were also IL-2 producers irrespective of the T4 or T8 phenotype. Our results show that human mammary carcinomas contain many infiltrating T cells with cytolytic potential. Interestingly, among the proliferating cytolytic T cell clones (56% of the microcultures), many expressed the T4+/T8– phenotype. These findings may indicate that the in situ cytolytic reaction (against unknown antigens) is associated preferentially with class II antigens.Fogarty International Fellow of NIH, 1984–1985; on leave from Dept of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pa, USA     

Telomerase activity in Kaposi's sarcoma, squamous cell carcinoma, and basal cell carcinoma

Patients with acquired immune deficiency syndrome (AIDS) often develop Kaposi's sarcoma (KS), an unusual skin tumor. The malignant nature of KS has long been disputed. Telomerase activity that maintains telomere length and ensures chromosomal stability, a frequently appearing marker in human malignancies, has been proposed to play a critical role in supporting continued cell growth, hence formation of tumors. We examined telomerase activity in tissue extracts from 22 KS, 10 squamous cell carcinoma (SCC), and 22 basal cell carcinoma (BCC) using the telomeric repeat amplification protocol (TRAP). All of the tumor tissues were previously cryopreserved at -80 degrees C. In this study, all tumor samples tested were positive for telomerase activity. Consistent with the presence of the enzyme activity, the skin tumors had relatively long telomeres. Inhibitors in the tissue extracts of some samples needed to be diluted or extracted by phenol before the enzyme activity was detected in the TRAP assay. All KS as well as two other skin carcinoma samples revealed positive telomerase activity. Our finding supports telomerase's role in tumor cell immortality and suggests the true neoplastic nature of KS.     

Therapeutic vaccination against metastatic renal cell carcinoma by autologous dendritic cells: preclinical results and outcome of a first clinical phase I/II trial

In this study we have presented in vitro data and results of a preliminary clinical trial using dendritic cells (DC) in patients with progressive metastatic renal cell carcinoma. DC precursor cells were obtained from peripheral blood mononuclear cells (PBMC). DC were pulsed with autologous tumor cell lysate if available. In total, 15 patients were treated with a median of 3.95 x 10(6) DC administered and ultrasound-guided into a lymph node or into adjacent tissue. Seven patients remained with progressive disease (PD), 7 patients showed stable disease (SD), and one patient displayed a partial response (PR). Most interestingly, the patient who was treated with the highest number of DC (14.4 x 10(6) DC/vaccine) displayed a PR. Delayed-type hypersensitivity (DTH) reaction using autologous tumor lysate was positive in 3 out of 13 patients, including the patient with PR. Two out of 3 patients receiving additional treatment with keyhole limpet hemocyanin (KLH) showed reactivity to KLH after vaccination. CD3+CD4+ and CD3+CD28+ cells as well as the proliferation rate of peripheral blood lymphocytes (PBL) increased significantly in the blood of patients during therapy. In conclusion, our observations confirm the capability of tumor-lysate pulsed autologous DC vaccines to stimulate an immune response in patients with metastatic renal cell carcinoma even in the presence of a large tumor burden. The lack of adverse effects together with immunologic effects support further investigation of this novel therapeutic approach. Further studies are necessary to demonstrate clinical effectiveness in cancer patients, in particular in patients with less advanced disease.     

Interleukin-2 expanded lymphocytes from lymph node and tumor biopsies of human renal cell carcinoma, breast and ovarian cancer

Adoptive immunotherapy with immune effector cells has proved to be potent for treatment of tumors, however neither the attendant criteria for potential clinical efficacy of the injected cells, nor the method to prepare these cells are presently well established. Our procedure of collecting lymphocytes from biological samples, was based on the use of low IL-2 concentrations (90 to 150 IU/ml) and on the stringent separation of lymphocytes from tumor cells at the very early stages of their outgrowth in culture. When lymphocytes were derived from tumor biopsies (TIL), we observed differences depending on the histological type of tumor. In renal cell carcinoma, natural killer cells were expanded in 4/11 biopsies contrary to what was observed in breast cancer (92 +/- 5% of T lymphocytes from 9 biopsies). The outgrowth of lymphocytes from breast tumors was slower and lower than from renal carcinomas. The autologous tumor cell line was more difficult to obtain from breast carcinoma (23%) than from renal cell carcinoma (61%) biopsies. For ovarian cancer, short-term culture of tumor cells could be obtained for half of the tumor-invaded biological samples. Eight of the 23 tumor-derived cultures contained more than 40% CD8 T. TIL were consistently cytolytic each time they could be evaluated. For ascitic and pleural fluids, data were of similar range. In ascitic-derived cultures, tumor cells and antigen-presenting cells are present and can be supposed to rechallenge T cells with tumor antigens. Lymphocytes derived from lymph nodes could be expanded to a larger number than TIL. However, only 1/18 of these cultures contained more than 40% CD8 T. The presence of few tumor cells in this culture was in favor of significant specific and non-specific cytotoxicity in RCC lymph node cultures and higher percentages of CD8 T in breast cancer lymph nodes. Correlations could not be established between CD8 T percentages and specific in vitro cytotoxicity in our polyclonal populations. Our conclusion is that phenotypic and functional quality of lymphocytes is of interest when the T cells are derived 1) from tumors (RCC, breast or ovarian cancer) and isolated very early to avoid inhibitor factors secreted from tumor cells or 2) from lymph nodes and ascitic and pleural fluids when very few tumor cells are co-cultivated with lymphocytes at initial steps of culture. Final expansion to a number of lymphocytes suitable for therapy (> 109) could be attained in a second step of the procedure by the use of 1,000 IU/ml IL-2 each time it was assayed with 50.106 lymphocytes. In view of these data it appears that phenotypic and functional changes occur during culture depending on the presence of a particular ratio of tumor antigens. This could be artificially reproduced.     

Giant basal cell carcinoma of the forehead: a case report

Giant basal cell carcinoma (GBCC) is defined as a tumor 5cm or greater in diameter. They present less than 1% of all basal cell carcinomas. We present a case of an 85-year-old male patient with a giant ulcerating tumor of the left forehead (measuring 7x6 cm). Under local anesthesia tumor was surgically excised. No involvement of the underlying periostal or bone structure was noted. Pathohystological exam revealed the giant basal cell carcinoma, with free surgical margins. Giant basal cell carcinomas are rare tumors and are usually result of a long duration and patient neglect. In comparison to the ordinary basal cell carcinoma these tumors have a higher metastatic potential. Surgical resection with negative surgical margin is the best possible treatment option.     

Cytolytic response of human T cells against allogeneic small cell lung carcinoma treated with interferon gamma

Summary Human lymphocytes stimulated in vitro by allogeneic small cell lung carcinoma cell lines did not show any significant cytolytic activity against the stimulator tumor cells. However, a high level of lysis was observed when both stimulator and target small cell lung carcinoma cells were pretreated with inferferon , which increased considerably the expression of major histocompatibility class I molecules by these cells. The demonstration that small cell lung carcinoma cells can be lysed by cytolytic T lymphocytes, suggests that it will be feasible to study the autologous T cell response of patients against this tumor.