Is Mycobacterium tuberculosis carcinogenic to humans?

We highlight the ability of the tuberculosis (TB) causing bacterial pathogen, Mycobacterium tuberculosis (Mtb), to induce key characteristics that are associated with established IARC classified Group 1 and Group 2A carcinogenic agents. There is sufficient evidence from epidemiological case-control, cohort and meta-analysis studies of increased lung cancer (LC) risk in pre-existing/active/old TB cases. Similar to carcinogens and other pathogenic infectious agents, exposure to aerosol-containing Mtb sprays in mice produce malignant transformation of cells that result in squamous cell carcinoma. Convincing, mechanistic data show several characteristics shared between TB and LC which include chronic inflammation, genomic instability and replicative immortality, just to name a few cancer hallmarks. These hallmarks of cancer may serve as precursors to malignant transformation. Together, these findings form the basis of our postulate that Mtb is a complete human pulmonary carcinogen. We also discuss how Mtb may act as both an initiating agent and promoter of tumor growth. Forthcoming experimental studies will not only serve as proof-of-concept but will also pivot our understanding of how to manage/treat TB cases as well as offer solutions to clinical conundrums of TB lesions masquerading as tumors. Clinical validation of our concept may also help pave the way for next generation personalized medicine for the management of pulmonary TB/cancer particularly for cases that are not responding well to conventional chemotherapy or TB drugs.

Characteristics of Hepatocellular Carcinoma Aggressiveness Factors in Turkish Patients.

A large cohort of hepatocellular carcinoma (HCC) patients from several collaborating Turkish institutions were examined for the tumor parameters of maximum diameter (MTD), portal vein thrombosis (PVT), and α-fetoprotein (AFP) levels. A relationship was found between MTD and blood platelet levels. Patients with large ≥5 cm tumors who had normal platelet levels had significantly larger tumors, higher percent of PVT, and significantly lower blood total bilirubin and liver cirrhosis than similar ≥5 cm tumor patients having thrombocytopenia. A comparison of patients with and without PVT showed significantly larger tumors, greater multifocality, blood AFP, and C-reactive protein levels, and, interestingly, lower HDL levels in the patients with PVT. Fifty-eight percent of the total cohort had AFP levels ≤100 IU/mL (and 42.1% had values ≤20 IU/mL). These patients had significantly smaller tumors, less tumor multifocality and percent PVT, lower total bilirubin, and less cirrhosis. There was considerable geographic heterogeneity within Turkey in the patterns of HCC presentation, with areas of higher and lower hepatitis B virus, hepatitis D virus, cirrhosis, and tumor aggressiveness parameters. Turkish patients thus have distinct patterns of presentation, but the biological relationships between MTD and both platelets and bilirubin levels are similar to the relationships that have been reported in other ethnic patient groups.

Pan-Cancer Survey of Tumor Mass Dormancy and Underlying Mutational Processes.

Tumor mass dormancy is the key intermediate step between immune surveillance and cancer progression, yet due to its transitory nature it has been difficult to capture and characterize. Little is understood of its prevalence across cancer types and of the mutational background that may favor such a state. While this balance is finely tuned internally by the equilibrium between cell proliferation and cell death, the main external factors contributing to tumor mass dormancy are immunological and angiogenic. To understand the genomic and cellular context in which tumor mass dormancy may develop, we comprehensively profiled signals of immune and angiogenic dormancy in 9,631 cancers from the Cancer Genome Atlas and linked them to tumor mutagenesis. We find evidence for immunological and angiogenic dormancy-like signals in 16.5% of bulk sequenced tumors, with a frequency of up to 33% in certain tissues. Mutations in the CASP8 and HRAS oncogenes were positively selected in dormant tumors, suggesting an evolutionary pressure for controlling cell growth/apoptosis signals. By surveying the mutational damage patterns left in the genome by known cancer risk factors, we found that aging-induced mutations were relatively depleted in these tumors, while patterns of smoking and defective base excision repair were linked with increased tumor mass dormancy. Furthermore, we identified a link between APOBEC mutagenesis and dormancy, which comes in conjunction with immune exhaustion and may partly depend on the expression of the angiogenesis regulator PLG as well as interferon and chemokine signals. Tumor mass dormancy also appeared to be impaired in hypoxic conditions in the majority of cancers. The microenvironment of dormant cancers was enriched in cytotoxic and regulatory T cells, as expected, but also in macrophages and showed a reduction in inflammatory Th17 signals. Finally, tumor mass dormancy was linked with improved patient survival outcomes. Our analysis sheds light onto the complex interplay between dormancy, exhaustion, APOBEC activity and hypoxia, and sets directions for future mechanistic explorations.

Retrograde Abdominal Hysterectomy.

The basic procedure of abdominal hysterectomy is extrafascial hysterectomy, and intrafascial hysterectomy (Aldridge operation) and retrograde hysterectomy are performed as applied surgical procedures. The Aldridge operation and retrograde hysterectomy are performed when strong adhesion is present around the uterus. Retrograde hysterectomy is also useful when the cervicovaginal junction is not clearly felt by palpation, such as when uterine rupture immediately occurs after vaginal delivery or when a large tumor mass is present in the vagina.

Adaptive hysteresis thresholding segmentation technique for localizing the breast masses in the curve stitching domain.

BACKGROUND AND OBJECTIVE: Massive work by distinguished researchers in the domain of breast segmentation has been proposed. However, no significant solution reduces the limitations of the false positive rate of cancerous cells in the breast body for probing the abnormalities of particular features. This problem is challenging in its nature and essential to be solved. It is needed to reach the optimal measurements of the breast parenchyma, the breast patchy regions of the mammogram, or the breast registration for searching of precise oddities. METHODS: In this work, we propose a novel approach for observing the abnormal breast cells identification with high sensitivity. A cancer tumor often produces a specific protein in the blood that serves as a marker for the cancer cells. These cells break off from the cancer and move into the blood stream. However, presence of pectoral muscle in breast mammogram highly affects the detection process of breast tumor. A novel aspect of the proposed method is that the curve stitching technique is developed for removing of pectoral muscle. Following this, an adaptive hysteresis thresholding is used for segmentation. This hybrid technique is used for segmenting a breast region of digital mammogram with suppression of pectoral muscle. RESULTS: The proposed method attains a highest sensitivity rate of 96.6% for the MIAS dataset and 96.4% for the DDSM dataset as compared to existing methods. CONCLUSION: The main idea behind this is to improve the threshold based segmentation techniques to create an adaptive threshold and apposite templates, in order to conserve tumor salient features about suspicious regions to classify benign and malignant mass in mammogram. First, a spline based curve fitting is applied on edges of the breast parenchyma and fill the region with a very low intensity value and map on original image to preserve the original intensity of breast region free of pectoral muscle. The results of the experiments show that the proposed segmentation technique is efficient when tested on MIAS and DDSM dataset.

Effects of STC1 overexpression on tumorigenicity and metabolism of hepatocellular carcinoma.

Stanniocalcin-1 (STC1) is a paracrine factor associated with inflammation and carcinogenesis. Using clinicopathological data, we previously reported that a greater expression of STC1 in hepatocellular carcinoma (HCC) was significantly correlated with smaller tumor size. The underlying mechanism on the correlation is not known. In this study, using a metastatic HCC cell-line (MHCC-97L, P) and lentiviral vector mediated-STC1 overexpression, the inoculation of STC1-overexpressing MHCC-97L (S1) cells in a nude mice xenograft model demonstrated reductions in tumor mass and volume. As compared with P cells, S1 cells exhibited epithelial phenotype with significantly lower plating efficiency and reduced migratory and proliferative potential. Using coulter counter for cell-sizing, S1 cells (17.6 µm) were significantly smaller than P cells (19.6 µm). Western blot analysis revealed that S1 cells exhibited reduced expression level of phosphorylated ribosomal protein S6 (p-rpS6). Moreover, an inhibition of the upstream kinase p70S6K was evident with the dephosphorylation of Thr389 in the linker domain of the kinase. The inhibition of p70S6K/p-rpS6 pathway was accompanied with reduced cellular ATP level and increase of p-AMPK in S1 cells. Significantly lower rates of glycolysis and extracellular O2 consumption in S1 cells exhibited a lower cellular energy status. Since a faster rate of ATP production is essential to support cancer growth and metastasis, the present study identified the effect of STC1-overexpression on reducing energy metabolism, leading to an activation of AMPK pathway but an inhibition of p70S6K/p-rpS6 signaling to reduce tumor growth.

Tracking Functional Tumor Cell Subpopulations of Malignant Glioma by Phasor Fluorescence Lifetime Imaging Microscopy of NADH.

Intra-tumoral heterogeneity is associated with therapeutic resistance of cancer and there exists a need to non-invasively identify functional tumor subpopulations responsible for tumor recurrence. Reduced nicotinamide adenine dinucleotide (NADH) is a metabolic coenzyme essential in cellular respiration. Fluorescence lifetime imaging microscopy (FLIM) of NADH has been demonstrated to be a powerful label-free indicator for inferring metabolic states of living cells. Using FLIM, we identified a significant shift towards longer NADH fluorescence lifetimes, suggesting an increase in the fraction of protein-bound NADH, in the invasive stem-like tumor-initiating cell (STIC) subpopulation relative to the tumor mass-forming cell (TMC) subpopulation of malignant gliomas. By applying our previously studied model to transition glioma from a majority of STIC to a majority of TMC in serum-adherent culture conditions following serial passages, we compared changes in NADH states, cellular respirations (oxidative phosphorylation and glycolysis), EGFR expression, and cell-growth speed over passages. We identified a significant positive correlation between free-NADH fraction and cell growth, which was related to an increase of TMC fraction. In comparison, the increase of EGFR and cellular respirations preceded all these changes. In conclusion, FLIM of NADH provides a non-invasive method to monitor the dynamics of tumor heterogeneity before and after treatment.

The treatment with pasireotide in Cushing's disease: effects of long-term treatment on tumor mass in the experience of a single center.

Pasireotide is the first medical therapy officially approved for the treatment of adult patients with Cushing's disease (CD) who experienced a failure of pituitary surgery or are not candidates for surgery and require medical therapeutic intervention. The current study aimed at investigating the effects of long-term treatment with pasireotide (up to 24 months) on tumor mass in a group of patients with CD, participating to a phase III study. Fourteen CD patients entered the phase III clinical trial CSOM230B2305 at Naples Center, and eight (seven women, one man, aged 38.9 ± 17.6 years), including seven with a microadenoma and one with a macroadenoma, received treatment with pasireotide at the dose of 600-1200 µg bid for at least 6 months, and were considered for the analysis of the study. These eight patients were subjected to the evaluation of pituitary tumor volume by pituitary MRI, together with the evaluation of urinary cortisol levels, at baseline and every 6 months for the entire period of treatment. Pasireotide treatment induced full disease control in 37.5 % and partial disease control in 37.5 % after 6 months, whereas full and partial disease control after 12 months was obtained in 28.6 % and in 57.1 % of patients, respectively. A significant (>25 %) reduction in tumor volume was found in 62.5 % and in 100 % of patients, after 6 and 12 months, respectively. In particular, after 6 months, a slight tumor shrinkage (between 25.1 and 50 %) was observed in 25 %, moderate (50.1-75 %) in 25 %, and marked (>75 %) in 12.5 % of patients, whereas after 12 months, a slight tumor shrinkage was observed in 43 %, moderate in 14 %, and marked in 43 % of patients. In 25 % of patients (two patients), a marked tumor shrinkage was recorded, with tumor mass disappearance in one case; this tumor shrinkage was associated to rapid and sustained biochemical remission up to 24 months of continuous pasireotide treatment. These two cases represent the first cases with a documentation of such a notable effect of pasireotide on tumor mass. Pasireotide induces significant tumor shrinkage in 62.5 % of patients after 6 months and in 100 % of patients after 12 months, and occasionally induces a radiological disappearance of the tumor. This evidence supports and strengthens the role of pasireotide as medical treatment specifically addressed to patients with CD, particularly in those who had unsuccessful pituitary surgery, or are not candidates for surgery.

The effect of interleukin 36 gene therapy in the regression of tumor.

BACKGROUND: Cancer immunotherapy attempts to stimulate the immune system to reject and destroy tumors and is one of the cancer treatment strategies. Recently, interluekin36 (IL36) has been used as immunotherapeutic agents in cancer gene therapy. Present study investigated that the IL36 gene therapy effects on the regression of tumor masses in mouse model. Aim of this study is determination of the gene therapy effects by IL36 in the regression of tumor masses in mouse model. METHODS: To study the therapeutic efficacy of this cytokine, WEHI-164 tumor cells were transected with mIL36 plasmids. ELISA test was used to check cytokine production by transected cells. To establish fibro sarcoma mouse model, Tumoral transfected cells were injected subcutaneously to inoculate tumor in BALB/C mice. Tumor volumes were measured by caliper. Mice were sacrificed and tumors were extracted. The expression of IL36 and IFN-γ was studied with Real-time PCR and immunoblotting. The expression of Ki-67 (a tumor proliferation marker) in tumor masses was studied by immunohistochemistry staining. In this study we had 2 groups which are treated with IL-36 and Untreated with IL-36 as a blank. RESULTS: The group treated with IL36 indicated decrease of tumor mass volume (p<0.001). The results of western blotting and real-time PCR showed the IL36 expression increased in the group treated with IL36 (with relative expression of 1.9). CONCLUSION: Immunohistochemistry staining indicated that the Ki-67expression has been reduced in the group interfered with IL36. IL36 gene therapy has therapeutic effects on the regression of tumor masses in fibro sarcoma mouse model.

Unilateral pulmonary hilar tumor mass: is it always lung cancer?

Sarcoidosis is a multisystem inflammatory disease of unknown etiology, characterized by noncaseating epithelioid cell granulomas. In sarcoidosis, the most common radiological findings are mediastinal and bilateral hilar lymph node enlargement. We present a case of sarcoidosis with a rare radiological aspect of pulmonary hilar tumor mass.A 54-year-old female patient, active smoker (40 packs/year), with a history of cutaneous lupus, was admitted in our institute for progressive dyspnea and dry cough. At admission physical examination and laboratory tests were normal. Pulmonary function tests diagnosed an obstructive syndrome. Chest X-ray showed a tumor mass of the right pulmonary hilum. Transbronchial biopsy was nondiagnostic. HRCT-scan showed a tumor mass in the right hilum, which raised the suspicion of a lung cancer. PET-CT scan revealed a high metabolic activity of the tumor mass and of a paratracheal right lymphadenopathy. Lymph node biopsy by mediastinoscopy showed noncaseating epithelioid-cell granulomas, sustaining the diagnosis of sarcoidosis. The outcome was favorable, with spontaneous remission without treatment, but with a relapse that responded after systemic corticotherapy.In conclusion, even if a tumor mass in the pulmonary hilum is highly suggestive of lung cancer, a positive diagnosis should be made only after histological examination, because other benign conditions, like sarcoidosis, could have such an aspect.

Phenotypic Categorization and Profiles of Small and Large Hepatocellular Carcinomas.

We used a database of 4139 Taiwanese HCC patients to take a new approach (Network Phenotyping Strategy) to HCC subset identification. Individual parameters for liver function tests, complete blood count, portal vein thrombosis, AFP levels and clinical demographics of age, gender, hepatitis or alcohol consumption, were considered within the whole context of complete relationships, being networked with all other parameter levels in the entire cohort. We identified 4 multi-parameter patterns for one tumor phenotype of patients and a separate 5 multi-parameter patterns to characterize another tumor phenotype of patterns. The 2 subgroups were quite different in their clinical profiles. The means of the tumor mass distributions in these phenotype subgroups were significantly different, one being associated with larger (L) and the other with smaller (S) tumor masses. These significant differences were seen systematically throughout the tumor mass distributions. Essential and common clinical components of L-phenotype patterns included simultaneously high blood levels of AFP and platelets plus presence of portal vein thrombosis. S included higher levels of liver inflammatory parameters. The 2 different parameter patterns of L and S subgroups suggest different mechanisms; L, possibly involving tumor-driven processes and S more associated with liver inflammatory processes.

Mechanisms of Metastatic Tumor Dormancy.

Tumor metastasis can occur years after an apparent cure due to a phenomenon known as metastatic tumor dormancy; in which tumor masses or individual tumor cells are growth restricted for extended periods of time. This period of dormancy is induced and maintained by several mechanisms, including: (1) Tumor microenvironment factors such as cytokine expression, immunosurveillance and angiogenesis; (2) Metastasis suppressor gene activity; and (3) Cancer therapeutics. Disseminated tumor cells (DTC) are the key cells that result in dormant tumors. However, many challenges exist towards isolating DTCs for mechanistic studies. The main DTC that may represent the dormant cell is the cancer stem cells (CSC) as they have a slow proliferation rate. In addition to limited knowledge regarding induction of tumor dormancy, there are large gaps in knowledge regarding how tumors escape from dormancy. Emerging research into cancer stem cells, immunotherapy, and metastasis suppressor genes, may lead to new approaches for targeted anti-metastatic therapy to prevent dormancy escape. Overall, an enhanced understanding of tumor dormancy is critical for better targeting and treatment of patients to prevent cancer recurrence.

Presentación tumoral de actinomicosis pélvica / Tumor Presentation of Pelvic Actinomycosis

La actinomicosis es una enfermedad crónica granulomatosa poco común causada por bacterias gram positivas, anaeróbicas, microaerófilas principalmente del género Actynomices. Se presenta el caso de una mujer de 49 años de edad, con cuadro clínico de aproximadamente 4 meses de evolución dado por estreñimiento, asociado a tenesmo rectal durante la defecación y pérdida de peso, portadora de dispositivo intrauterino desde hace 7 años. En el examen físico se encontró la presencia de una masa, de bordes mal definidos, en flanco y fosa iliaca derechos, y en hipogastrio, no dolorosa a la palpación. El ultrasonido abdominal reportó una masa en lóbulo caudado hepático y una estructura de contornos mal definidos en íntimo contacto con techo vesical y fundus uterino. La biopsia de lesión reveló actinomicosis. Se confirma la actinomicosis en una paciente con masa palpable en hipogastrio y dispositivo intrauterino colocado(AU)

Actinomycosis is an uncommon granulomatous chronic disease caused by gram-positive, anaerobic, microaerophilic bacteria, mainly of the genus Actynomices. We present the case of a 49-year-old woman with a clinical condition of approximately 4 months of evolution due to constipation, associated with rectal tenesmus during defecation and weight loss, carrier of an intrauterine device for 7 years. In the physical examination, the presence of a mass was found, with poorly defined edges, flank anda iliac fossa right, and hypogastrium, not painful on palpation. Abdominal ultrasonography reported a mass in the hepatic caudate lobe and a structure of ill-defined contours in intimate contact with the bladder roof and uterine fundus. The lesion biopsy revealed actinomycosis. It was confirmed in a patient with palpable mass in hypogastrium and intrauterine device placed(AU)

Presentación tumoral de actinomicosis pélvica / Tumor Presentation of Pelvic Actinomycosis

La actinomicosis es una enfermedad crónica granulomatosa poco común causada por bacterias gram positivas, anaeróbicas, microaerófilas principalmente del género Actynomices. Se presenta el caso de una mujer de 49 años de edad, con cuadro clínico de aproximadamente 4 meses de evolución dado por estreñimiento, asociado a tenesmo rectal durante la defecación y pérdida de peso, portadora de dispositivo intrauterino desde hace 7 años. En el examen físico se encontró la presencia de una masa, de bordes mal definidos, en flanco y fosa iliaca derechos, y en hipogastrio, no dolorosa a la palpación. El ultrasonido abdominal reportó una masa en lóbulo caudado hepático y una estructura de contornos mal definidos en íntimo contacto con techo vesical y fundus uterino. La biopsia de lesión reveló actinomicosis. Se confirma la actinomicosis en una paciente con masa palpable en hipogastrio y dispositivo intrauterino colocado(AU)

Actinomycosis is an uncommon granulomatous chronic disease caused by gram-positive, anaerobic, microaerophilic bacteria, mainly of the genus Actynomices. We present the case of a 49-year-old woman with a clinical condition of approximately 4 months of evolution due to constipation, associated with rectal tenesmus during defecation and weight loss, carrier of an intrauterine device for 7 years. In the physical examination, the presence of a mass was found, with poorly defined edges, flank anda iliac fossa right, and hypogastrium, not painful on palpation. Abdominal ultrasonography reported a mass in the hepatic caudate lobe and a structure of ill-defined contours in intimate contact with the bladder roof and uterine fundus. The lesion biopsy revealed actinomycosis. It was confirmed in a patient with palpable mass in hypogastrium and intrauterine device placed(AU)

The negative prognostic impact of bone metastasis with a tumor mass

OBJECTIVE: Typically, bone metastasis causes osteolytic and osteoblastic lesions resulting from the interactions of tumor cells with osteoclasts and osteoblasts. In addition to these interactions, tumor tissues may grow inside bones and cause mass lesions. In the present study, we aimed to demonstrate the negative impact of a tumor mass in a large cohort of patients with bone metastatic cancer. METHODS: Data from 335 patients with bone metastases were retrospectively reviewed. For the analysis, all patients were divided into three subgroups with respect to the type of bone metastasis: osteolytic, osteoblastic, or mixed. The patients were subsequently categorized as having bone metastasis with or without a tumor mass, and statistically significant differences in median survival and 2-year overall survival were observed between these patients (the median survival and 2-year overall survival were respectively 3 months and 16% in patients with a tumor mass and 11 months and 26% in patients without a tumor mass; p<0.001). RESULTS: According to multivariate analysis, the presence of bone metastasis with a tumor mass was found to be an independent prognostic factor (p=0.011, hazard ratio: 1.62, 95% confidence interval: 1.11–1.76). Bone metastasis with a tumor mass was more strongly associated with osteolytic lesions, other primary diseases (except for primary breast and prostate cancers), and spinal cord compression. CONCLUSION: Bone metastasis with a tumor mass is a strong and independent negative prognostic factor for survival in cancer patients. .

Reporte de caso clínico: hemangioendotelioma esplénico de células epitelioide. Primer reporte latinoamericano / Clinical case report: splenic hemangioendothelioma of epithelioid cells

El Hemangioendotelioma esplénico es una rara neoplasia sarcomatosa de etiología idiopática y malignidad intermedia, entre el hemangioma y el hemangioendoteliosarcoma. Se presenta el caso de un paciente de sexo masculino de 54 años que acude a consulta por presentar dolor postraumático y una masa tumoral esplénica palpable. Diagnóstico prequirúrgico compatible con una lesión quística vascular. Histológicamente está compuesto por células redondas atípicas epitelioides con núcleos grandes y nucléolos prominentes, acompañado por proliferación de canales vasculares y, en ciertas áreas, con células fusiformes elongadas. En estudio de inmunohistoquímica se muestra células tumorales positivas para el antígeno CD34 (FLEX 2x5 DAB) y anticuerpos de vimentina. El componente estromal muestra evidente diferenciación miofibroblástica. A pesar de tratarse de una patología sumamente infrecuente (solo siete casos reportados a nivel mundial) posee un buen pronóstico y no se han documentado recidivas. Se han descrito tres variantes histopatológicas: epitelioide, kaposiforme y retiforme. Se realiza el diagnóstico diferencial con el tipo kaposiforme por cuanto es evidente la ausencia de luces vasculares en media luna, así como los respectivos depósitos de hemosiderina y se descarta angiosarcoma al no observarse células anaplásicas.

The splenic hemangioendothelioma is a rare sarcomatous neoplasm of idiopathic etiology and intermediate malignancy, between hemangioma and hemangioendothelioma. This is the case of a 54-year-old male patient who goes to the doctor with post-traumatic pain disorder and a palpable splenic tumor. The preoperative diagnosis was compatible with a vascular cystic lesion. Histologically, it is composed of atypical epithelioid round cells with large nuclei and prominent nucleoli, accompanied by a proliferation of vascular channels and, in some areas, by elongated spindle cells. An immunohistochemistry study shows tumor cells that are positive for the CD34 antigen (FLEX 2x5 DAB) and Vimentin antibodies. The stromal component clearly shows myofibroblastic differentiation. Despite being a extremely rare disease (only seven cases reported worldwide) it has a good prognosis and recurrence has not been documented. Three histopathological variants have been described: epithelioid, kaposiform and retiform. A differential diagnosis is made with the kaposiform type because of the evident absence of “half-moon” vascular lumina, as well as the respective reservoirs of hemosiderin; angiosarcoma is ruled out because of the absence of anaplastic cells.

The Effects of the Tumor Mass Size Inoculated in Immunologically Competent Balb/c Mice on Delayed-type Hypersensitivity Response

BACKGROUND: Based on outstanding progresses in animal experiments, vaccines for some human tumors have been developed. However, clinical effects of these vaccines have been far below than expected. This discrepancy might come from differences between animal models and human patients with respect to immunocompetency. The immune status of mice after tumor inoculation has not been well studied, which make us cautious in interpreting and applying the results from mice to human. We evaluated cell-mediated immune responses in mice after tumor cell inoculation. METHODS: Mice were inoculated with TA3Ha, CT26, or 4T1. Delayed-type hypersensitivity (DTH) responses were induced 2-4 weeks after inoculation using 2,4-dinitro-1-fluorobenzene as an antigen. The relationships between the severity of DTH responses and the duration of tumor inoculation or the size of tumor mass were analyzed. RESULTS: In TA3Ha groups, DTH response was elevated 2 weeks after inoculation, but depressed after 4 weeks, compared to the control group. When analyzed based on the sizes of tumor masses elicited, DTH responses were inversely related to the mass size, especially in those greater than 10 mm in diameter. In CT26 groups, while the duration after inoculation did not affect the severity of DTH responses, those with large mass showed depressed responses regardless the duration of inoculation. 4T1 cells grew so slowly that the size of tumor mass was small even 4 weeks after inoculation, and this group showed much higher DTH responses compared to that of tumor-free group. CONCLUSION: At least in an experimental setting where tumor model was induced by inoculating tumor cell lines into immunologically competent mice, the host immune response was elevated in early stage, and then depressed in late stage when the mass grew over a critical size.

A Case of Multiple Myeolma with Huge Tumor Mass in Clavicle / 대한정형외과학회잡지

Multiple myeloma is considered to be the most common primary malignant bone tumor which has the flat bone as a predilection site in old ages. We experienced a case of an unsual multiple myeloma which formed a huge tumor mass on medial end of left clavicle. The tumor mass together with medial half of the clavicle was excised completely. We have discussed the rationale for the excision of the clavicle.

A Case of Congenital Self-Healing Reticulohistiocytosis / 대한피부과학회지

We report a case of congenital self-healing reticulohistiocytosis in a newborn male, who showed numerous reddish brown papulonodules on the whole of his body and an extremely large tumor mass on the left sole. No extracutaneous involvement was found. All lesions involuted spontaneously within two months. Histopathologically, multiple histiocytes with abundant eosinophilic cytoplasm, multinucleated cells, and eosinophils were observed in the dermis. Immunohistochemical staining with S-100 protein showed positive.