Total thyroidectomy: Conventional Suture Ligation technique versus sutureless techniques using Harmonic Scalpel or Maxium.

OBJECTIVES: Harmonic Scalpel (HS) and Maxium (MAX) are surgical shears that enable simultaneous vessel sealing and tissue coagulation. This study compares the outcome of Total Thyroidectomy (TT) using Conventional Suture Ligation (CSL) technique versus (vs) two sutureless techniques; H S and MAX techniques in terms of safety, operative time, blood drainage volume, hospital stay and surgical complications. STUDY DESIGN: This is a prospective observational cohort study. SETTING: This study was performed in AL-Karama Teaching Hospital/College of Medicine/University of Wasit/Iraq. PATIENTS AND METHODS: This study was performed from June 2012 to 2015. A total of 80 patients, 60 patients were females and 20 patients were males (average/mean of age was 39/38 years). They underwent TT after been randomized into the following three groups: CSL group when Suture Ligation Technique was used, HS group when Harmonic Scalpel was used and MAX group when bipolar electrosurgery Maxium was used. RESULTS: The postoperative evaluation of operative time, blood drainage volume and surgical complications revealed no statistically significant differences between HS group & MAX group, but there were statistically significant differences between CSL group vs. HS and MAX groups. Operative time statistics showed significant differences between CSL vs. HS and MAX groups, 113 ± 10.9 minutes (min), 93 ± 13 min and 92 ± 10.6 min respectively, p-value < 0.001 and 95% confidence interval [CI] (92.3712, 101.6288). The postoperative blood drainage volumes were significantly different between the three groups: CSL group = 150 ± 12.7 ml, HS group = 89 ± 16.21 ml and MAX group = 118 ± 9.6 ml, P-value = 0.046 and 95% [CI] (89.9932, 99.6068). CONCLUSIONS: HS and MAX are safe, effective, and time-saving techniques. They are also associated with low blood loss and low complication rates. HS and MAX are good alternative techniques to CSL for thyroid surgery.

Synergistic anti-tumor activity of a novel immunomodulator, BCH-1393, in combination with cyclophosphamide.

N,N-dimethylaminopurine pentoxycarbonyl D-arginine (BCH-1393) is a novel low molecular weight synthetic immunomodulator that has been shown to significantly stimulate cytotoxic T-lymphocyte responses both in vitro and in vivo (Zacharie B, Gagnon L, Attardo G, Connolly TP, St-Denis Y, Penney CL. Synthesis and activity of 6-substituted purine linker amine immunostimulants. J. Med. Chem. 1997;40:2883-94). Prompted by this evidence, we extended evaluation of BCH-1393 for anticancer activity in syngeneic mouse experimental tumor models. Consistent with previous findings, in vitro assessment of BCH-1393 activity demonstrated a significant increase in the CTL responses in the range of 10(-9)-10(-5) M. Treatment of mice with four consecutive daily intraperitoneal injections at 25 and 50 mg/kg resulted in a significant increase of the relative percentage of blood CD4+, CD8+, NK and monocyte subsets without any evidence of toxicity. In vivo anti-tumor activity of BCH-1393 was evaluated, either alone or in combination with subtherapeutic doses of cyclophosphamide (Cy), against weakly immunogenic mouse breast carcinoma DA-3 and strongly immunogenic colon adenocarcinoma MC38. Daily intraperitoneal injection of BCH-1393 at 50 mg/kg alone was well tolerated but produced a relatively weak anti-tumor effect in both tumor models. However, a significant inhibition of tumor outgrowth and suppression of established tumor growth was observed when BCH-1393 was administered in combination with subtherapeutic doses of Cy. Combination treatment of 50 mg/kg BCH-1393 with 100 mg/kg Cy (given as single intravenous bolus injection) starting 2 days prior to DA-3 tumor cell inoculation prevented tumor outgrowth in 70-80% of treated mice. In the remaining 20-30% of mice that had developed tumors, a nearly complete (90%) tumor growth inhibition was observed at days 22-24 post tumor implant. In the MC38 tumor model, combination treatment of established tumors with BCH-1393 and Cy (CTX) at 50 mg/kg resulted in a significant delay in tumor growth compared to CTX treatment alone. The observed concomitant anti-tumor activity of BCH-1393 with cyclophosphamide warrants further investigation of this immunomodulator as an adjunctive treatment of cancer.

Inhibition of tumor growth with doxorubicin in a new orthotopically implanted human hepatocellular carcinoma model.

A number of human xenograft orthotopic models of hepatocellular carcinoma (HCC) have been previously established by growing histologically-intact patient specimens in nude mice. However, the availability of HBV and HCV negative human hepatocellular carcinoma specimens is scarce and the pattern of tumor growth in nude mice varies depending on the tumor type. In the present study, we have established a reproducible xenograft orthotopic model using a human HCC cell line designated HuT7-3 that was derived from two rounds of subcloning of the parental Huh-7 cell line. The tumor growth rate of the HuT7-3 cell line, grown at a primary subcutaneous site, was markedly higher than that of the Huh-7 parental cell line or the human hepatoblastoma Hep-G2 cell line. Furthermore, we have shown that doxorubicin, when administered intravenously, is efficient in inhibiting the development of subcutaneous tumor but leads to the regression of the orthotopic human HCC. Consequently, this novel HCC xenograft orthotopic model can be used for the evaluation of antitumor drugs.

Prevention of bladder tumor formation in mice by a novel bone marrow-derived factor, reptimed.

BACKGROUND: Reptimed is a novel, species-conserved, bone marrow-derived molecule which possesses anti-neoplastic activity. Previously, we established an orthotopic murine bladder tumor (MBT-2) model and reported accurate documentation of the presence and the extent of intravesical involvement of bladder tumor implants using magnetic resonance imaging (MRI) (1). Herein, we investigated the activity of exogenously administered Reptimed in the MBT-2 model. MATERIALS AND METHODS: Intravesicular and intraperitoneal administration of Reptimed concurrently with and following transurethral tumor cell implantation was performed and MBT-2 tumor response was assessed at several time points post tumor implant. RESULTS: Serial MRI scans of Reptimed-treated mice at days 14 to 33 post tumor transplant revealed significant inhibition of bladder tumor growth with no significant tumor growth observed by MRI on day 33 post-implant. The corresponding histological examination of the whole mount bladder sections revealed similar inhibitory effects of Reptimed with respect to the topography and depth of intravesical tumor involvement. In contrast, control, untreated bladders revealed extensive exophytic tumors with deeply invasive transitional cell carcinoma. CONCLUSIONS: These studies demonstrate the anti-tumor effect of Reptimed and highlight its importance as a potential therapy for cancer.

Synthesis and activity of dipeptides, linked to targeting ligands, as specific NK cell enhancers.

Water soluble analogues of the lipophilic immunostimulant, octadecyl D-alanyl-L-glutamine, BCH-527, were synthesized and evaluated for the ability to stimulate natural killer (NK) cells. One of these compounds in which the octadecyl chain of BCH-527 was replaced with a shorter chain alcohol, 6-(D-alanyl-L-glutaminylamino)hexan-1-ol, 9, displayed an in vitro stimulation of NK cells comparable to that of interleukin 2 (IL 2). However, when the hydroxyl of 9 was linked to L-fucose to yield 1-beta-[6-(D-alanyl-L-glutaminylamino)hex-1-yl]-L- fucopyranose (BCH-2537, 1), the observed stimulation of NK cells was greater than that observed with IL 2. Further evaluation of these compounds revealed that the improved in vitro activity of BCH-2537 was more pronounced in vivo. That is, while both compounds significantly increased splenic NK cells, only BCH-2537 significantly increased the activity of these cells in vivo. In terms of a structure-activity relationship, NK cell activity was sensitive to minor structural modifications. It was influenced by conservative substitutions within the dipeptide, the length of the hydrocarbon chain, and the functionality at the end of the chain. No other compound enhanced NK cell activity to the extent exhibited by BCH-2537, although a few were equipotent to 9.

Potent antitumor activity of a novel nucleoside analogue, BCH-4556 (beta-L-dioxolane-cytidine), in human renal cell carcinoma xenograft tumor models.

Beta-L-Dioxolane-cytidine (BCH-4556) is a novel anticancer nucleoside analogue with a stereochemically unnatural beta-L configuration. This compound was previously shown to have a potent antitumor activity in human prostate and hepatocellular xenograft tumor models (K. L. Grove et al., Cancer Res., 55: 3008-3011, 1995). Herein, we extended the efficacy validation of BCH-4556 to renal cell carcinoma (RCC) cell lines both in vitro and in vivo. In vitro cytotoxicity and proliferation inhibition determinations in human RCC cell lines CAKI-1, CAKI-2, 786-0, and A498 produced IC50 concentrations ranging from 15-35 nM. In vivo antitumor activity was consistent with the in vitro sensitivity. BCH-4556 was very effective in human RCC tumor xenograft models, including CAKI-1, A498, RXF-393, and SN12C carcinomas. Very good responses were observed in animals bearing CAKI-1, A498, and RXF-393 RCC tumors given i.p. doses of 10, 25, and 50 mg/kg twice a day for 5 days, with complete regression recorded in most of the animals tested. Curative activity was also observed, with 40-60% of animals remaining tumor free in all three RCC models at the day of study termination. Significant tumor shrinkage was also evident in the SN12C model. BCH-4556 efficacy evaluation in the orthotopic subrenal capsule tumor models demonstrated a potent tumor growth inhibition against human CAKI-1 xenografts and tumor stasis against mouse Renca tumors. BCH-4556 was also effective in inhibiting the growth of rebound CAKI-1 tumors after the administration of a second treatment cycle. The observed antitumor activity of BCH-4556 in several RCC human solid tumor xenografts, including the lethal RXF-393 model, warrants further investigation of this novel nucleoside analogue in clinical trials of RCC.

Genetically regulated response to intravesical bacillus Calmette Guerin immunotherapy of orthotopic murine bladder tumor.

PURPOSE: Genetically regulated host response to intravesical Bacillus Calmette Guerin (BCG) immunotherapy was assessed using the murine bladder tumor MM45T in Bcgr and Bcgs inbred congenic strains of mice. MATERIALS AND METHODS: Tumor detection and monitoring of treatment response to BCG was carried out using magnetic resonance imaging (MRI) of BALB/c (Bcgs allele) and BALB/c. CD2 (CD2) (Bcgr allele) mice implanted orthotopically with MM45T tumor cells. Intravesical BCG instillation (3 doses per week for 3 weeks) was used as prophylaxis against tumor implantation in both Bcgr and Bcgs strains and as definitive treatment against MRI-confirmed established tumors. Tumors implanted in both strains of untreated mice served as controls. Intravesical injection of BCG was also performed in established heterotopic subcutaneous tumors in both strains. Immunologic response in all groups was assessed by flow cytometric analysis of the bladder irrigation fluid cell composition, measuring CD4+ (helper/inducer) and CD8+ (cytotoxic/ suppressor) cell subsets. RESULTS: Intralesional injection of BCG into established heterotopic tumors showed growth inhibition in the Bcgs strain but not in the Bcgr strain. Intravesical BCG treatment against established orthotopic tumors showed significant tumor regression in the Bcgs strain compared to control but there was no effect in the Bcgr strain. CONCLUSION: The differential anti-tumor activity of BCG in the Bcgs and Bcgr congenic murine strains supports the notion that Bcg gene-controlled responsiveness to BCG innoculation determines, at least partially, the host response to immunotherapy. These results have potential clinical significance in patient selection for intravesical therapy for bladder cancer.

Mycobacterium cell wall: an alternative to intravesical bacillus Calmette Guerin (BCG) therapy in orthotopic murine bladder cancer.

PURPOSE: The antitumor effect of intravesical mycobacterium cell wall (MCW) therapy on orthotopic and heterotopic bladder tumors in the mouse was assessed with magnetic resonance imaging (MRI). MATERIALS AND METHODS: The live bacillus Calmette Guerin (BCG) organism was replaced with a cell wall extract derived from the outer capsule of Mycobacterium phlei. This alternative form of intravesical therapy was used with the aim of reducing the toxicity associated with the live mycobacterium organism without compromising efficacy. Response to multiple doses of intravesical MCW and BCG was assessed in mice with established MBT-2 tumors after transurethral tumor implantation. RESULTS: Serial MRI of BCG-treated mice revealed significant tumor regression. The MR images correlated well with the corresponding histology of the whole mount bladder sections. Treatment with MCW also resulted in significant inhibition of tumor growth compared with control untreated animals (p < 0.05) although the antitumor effect was less pronounced than that of live BCG. Treatment was well tolerated in the MCW group with no apparent ill effects. Flow cytometric (FCM) analysis of bladder washings with phenotype-specific monoclonal antibodies revealed predominantly a CD3+ T cell infiltrate in the control and BCG-treated as well as the MCW-treated mice. The CD4+ (helper/inducer) subset of T cells predominated over the CD8+ (suppressor/cytotoxic) subset in both the BCG- and MCW-treated animals, and the CD4+/CD8+ ratio in both of the treated groups differed significantly from that of the control untreated groups. CONCLUSION: Intravesical MCW appears to invoke a similar inflammatory response in the mouse bladder mucosa as the live BCG organism and retains an antitumor action. It deserves further evaluation as a potential antitumor agent against bladder cancer. A Phase II clinical trial is now underway.

Metallothionein expression and resistance to cisplatin in a human germ cell tumor cell line.

Expression of intracellular metallothionein (MT) has been linked to cis-diamminedichloroplatinum (cDDP) resistance in human germ cell tumor cell lines. To determine whether exposure to cDDP would select for cells with increased MT expression, the MT content of the human teratocarcinoma cell line T7800 was measured after development of resistance to cDDP by exposure to progressively higher drug concentrations (6.25-25 microM). cDDP-resistant cells (T7800R) had significantly higher MT mRNA and MT protein, increased resistance to killing by cDDP and altered in vitro growth kinetics compared to parental T7800 cells. cDDP resistance in a variety of other human tumor cell lines correlated with MT content, with no significant difference in glutathione level. These data indicate that selection in vitro for cDDP resistance in human germ cell tumors coselects for cells with enhanced MT content. However, selected cells differed in characteristics other than MT content. They had a slower growth rate and, although the rank order of MT level in T7800, T7800R and other human tumor cell lines correlated very well with cDDP resistance, differences in the level of MT expression did not correspond with differences in the absolute level of cDDP resistance. These results suggest that increased MT expression is concomitant with increased cDDP resistance in a variety of human tumor cell lines. However, measured differences in MT levels may not accurately reflect the degree of cDDP resistance differences among those cells.

Metallothionein in testicular germ cell tumors and drug resistance. Clinical correlation.

BACKGROUND: Metallothioneins (MT) are endogenous metalloproteins involved in the homeostasis of essential metals and detoxification of toxic metals. Some recent experimental studies suggested tumor resistance to cisdiamminedichloroplatin may be associated with overexpression of MT in the tumor. METHODS: The presence of MT in 33 primary testicular germ cell tumor specimens was assessed immunohistochemically using a rabbit polyclonal rat liver MT antibody that cross-reacted with human MT. The data were correlated with the patients' clinical course. RESULTS: Seminomas stained weakly or not at all for MT, regardless of the clinical stage. Most nonseminomas stained heavily for MT. The more advanced staged nonseminomas tended to stain more heavily for MT. CONCLUSIONS: In view of the considerable experimental evidence as well as some inferential clinical data involving MT in cis-diamminedichloroplatin resistance, there appears to be a role for MT in cis-diamminedichloroplatin resistance in germ cell tumors. Further studies to elucidate the role of MT in germ cell tumor chemoresistance are warranted.

Modulation of both cisplatin nephrotoxicity and drug resistance in murine bladder tumor by controlling metallothionein synthesis.

The role of metallothionein (MT) in cisplatin (cis-DDP) resistance and renal toxicity was investigated in C3H mice inoculated with mouse bladder tumor (MBT-2). C3H mice were inoculated s.c. with 1 x 10(6) MBT-2 cells/mouse on day 0. Mice were given injections of proparglyglycine (PPG) (500 mumol/kg s.c.) once a day for 3 days from day 7 to day 9 and with ZnSO4 (200 mumol/kg s.c.) once a day for 2 days from day 8 to day 9. cis-DDP (50 mumol/kg i.p.) was administered 10 days after MBT-2 cell inoculation. Since MT contents in the tumor and kidneys were significantly increased by administration of ZnSO4, both the antitumor activity of cis-DDP and its renal toxicity were reduced. However, coadministration of PPG reduced MT induction in tumor without affecting the level of renal MT. As a result, PPG could clearly overcome the MT-mediated cis-DDP resistance of tumors without compromising the protective effect exerted by renal MT on nephrotoxicity of the drug. It was suggested, therefore, that PPG may be a promising adjunct in cancer chemotherapy to overcome the drug resistance of tumors caused by the elevated level of MT.

Magnetic resonance imaging for detecting and treatment monitoring of orthotopic murine bladder tumor implants.

We assessed the feasibility of magnetic resonance imaging (MRI) for detection and treatment monitoring of early stage orthotopic murine bladder (MBT-2) tumor implants. Thirty mice were scheduled for imaging at six, 14, 18 and 21 days after tumor implantation. Using a volume imaging coil, MRI demonstrated very early orthotopic tumors, the detection of which would otherwise have been impossible by clinical signs only. Sequential accurate assessment of tumor size was achieved by inflation of the bladders with a fixed volume of Gadolinium-DTPA contrast. The presence of established MBT-2 intravesical tumors was confirmed by gross pathology and light microscopy of the corresponding whole mount bladder sections. Histological examination of the corresponding tumor specimens revealed the presence of transitional cell bladder carcinoma which correlated very well with the topography and depth of tumor involvement as indicated on MRI. The The mice tolerated repeated MR imaging well. Early tumors at day 14 were detectable on MRI (with serial tumor growth to day 21), with no clinical signs of disease. In a subsequent study, response to intravesical tumor necrosis factor alpha (TNF-alpha) immunotherapy was monitored with serial MRI. The serial MR images from six tumor-bearing mice (three controls and three TNF-alpha treated) have been selected to illustrate the consistent findings of this study. Sequential MRI scans of TNF-alpha treated mice revealed retardation of tumor growth that correlated well with the corresponding histologic examination. The orthotopic tumor and MRI model described is ideal for preclinical evaluation of new potential intravesical chemotherapy and immunotherapy agents.

Characterization of MBT-2 tumour cell "variant" resistant to tumour necrosis factor.

Previously we reported sensitivity of MBT-2 murine bladder tumour to tumour necrosis factor (TNF) in vivo and in vitro [8]. We showed that with prolonged exposure of cultured MBT-2 tumour cells to TNF, a resistant MBT-2 "variant" tumour cell population emerged in vitro. This concurred with the finding of transient in vivo cytotoxic effect of TNF against MBT-2 tumour. Herein, we delineate phenotypic changes in MBT-2 cells associated with TNF resistance. Parent MBT-2 (MBT-2P) and the TNF-resistant "variant" MBT-2R cells were compared in terms of in vitro sensitivity to TNF, DNA profile, karyotype and in vitro growth kinetics. We conclude that acquisition of resistance to TNF may be due to cell cycle derangement and differences in in vitro growth characteristics. DNA indices and karyotype of "variant" MBT-2R cells were not altered, indicating the anti-tumour action of TNF is not-mutagenic.

Concomitant treatment of MBT-2 bladder tumour by tumour necrosis factor alpha and interferon alpha in conjunction with delayed type hypersensitivity immunotherapy.

In our previous study [9], we reported the anti-tumour effect of TNF on mouse bladder tumour (MBT-2) both in vivo and in vitro. Inoculation of a single dose of TNF alone caused significant but transient tumour growth inhibition. Subsequent repeated doses of TNF did not sustain or augment the anti-tumour effect. The current experiments were undertaken to assess the anti-tumour activity of (i)-concomitant treatment of TNF-A and IFN-A against MBT-2 bladder tumour and (ii)-concomitant TNF + IFN-A treatment in conjunction with T-DTH (delayed-type hypersensitivity) immunotherapy. Systemic administration of multiple doses of TNF + IFN-A in vivo caused initial partial tumour regression followed by tumour growth inhibition up to 14 days following treatment. This combined treatment showed an enhanced anti-tumour effect compared to TNF-A treatment alone. Immunotherapy of MBT-2 tumour-bearing mice with T-DTH "immune" effector cells alone did not cause significant tumour growth inhibition. In contrast, concomitant administration of both T-DTH effector cells and TNF + IFN-A in MBT-2 tumour-bearing mice resulted in significant tumour growth inhibition for up to 16 days. The immune effector cells conferring immunotherapy were isolated from the spleens of tumour-immunized, "DTH-primed" animals and were characterized as Lyt 1+2- helper/DTH T cells (CD4+ phenotype). These cells mediate both DTH response to MBT-2 tumour antigens as well as anti-MBT-2 tumour protection. In vitro treatment of the "immune" cells with TNF-A resulted predominantly in the proliferation of Lyt 1+ T cells versus Lyt 2+ cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-tumor effect of tumor necrosis factor and its induction of tumor variant of MBT-2 transitional cell carcinoma of the bladder.

The effect of tumor necrosis factor (TNF), a potential anti-tumor agent, was assessed both in vivo and in vitro against MBT-2 transitional cell carcinoma of the bladder in C3H/HeHa mice. Systemic administration of either single or multiple doses of TNF into tumor bearing animals resulted in partial tumor regression and had a consistent but transient anti-tumor effect. Compared to control, untreated tumor bearing animals, TNF-treated tumor bearing mice had significantly smaller tumor volumes and slower tumor growth rates over the period of 12 days following TNF inoculation. No significant difference in tumor volumes and tumor growth rates between controls and TNF-inoculated mice was observed from day 12 to day 21 after TNF treatment. Assessment of TNF cytotoxicity against in vitro MBT-2 cell line using 3[H]-thymidine proliferation assay showed significant sensitivity of MBT-2 cells to treatment with TNF. A "Variant" MBT-2 cell line was derived by sequential culturing of the original MBT-2 cells in the presence of progressively higher concentrations of TNF in culture medium. Although the significant growth suppression on the MBT-2 tumor appears to be transient, further studies are warranted which may elucidate the immunologic and biologic behavior of TNF and this transplantable animal tumor.

In vivo induction of tumor variants by phorbol 12-myristate 13-acetate.

Malignant cells within solid tumors commonly exhibit phenotypic changes such as alterations in karyotype and acquisition of the ability to invade and to metastasize. We have used a fibrosarcoma, grown subcutaneously in C57BL/6 mice, to study the mechanisms underlying this phenotypic instability. Tumor-bearing animals were injected with phorbol myristate acetate (PMA) and then the tumors were transplanted to animals without further PMA treatment. These tumor cells were tum+, that is, unlike the parental tumors, they were able to grow in animals immunized against the parental tumors. This property was maintained for at least 6 tumor passages after the initial PMA injections. Thus, PMA appears to be able to induce an unstable tum+ phenotype in these cells at relatively high frequency.

Correlation of tumor specific delayed type hypersensitivity reaction and tumor protection to SV40-induced mKSA fibrosarcoma.

Mice immunized by excision of a primary, subcutaneously growing SV40-induced mKSA solid tumor which resisted challenge of homologous tumor cells administered at a contralateral site, were found to develop a specific DTH response to SV40 tumor associated transplantation antigens (TATA). In a two-way criss-cross experiment, this DTH response (assessed by direct challenge) was found to be one-way SV40 specific in that chemically induced, non SV40, MCA tumor failed to elicit a DTH response in mice primed by excision of mKSA tumor. These mice also showed a corresponding one-way specific protection against challenge with live homologous mKSA sarcoma cells. In contrast immunization and challenge of MCA-excised mice with either MCA or mKSA tumor cells, exhibited cross-reactivity in both DTH response and protection against either tumor. Unlike this cross-immunity by the direct challenge method, transfer of "immune" spleen cells from mKSA or MCA excision-primed mice demonstrated a specific DTH response and protection to the original immunizing, homologous but not heterologous tumor. Tumor resistant, DTH-primed mice remained DTH reactive to the primary tumor cells over a period of 4 weeks. Characterization of the splenic T-DTH cells in mice primed by excision of mKSA tumor, indicated a Lyt 1+2+ phenotype of cells conferring both the DTH response and the immune protection against mKSA sarcoma in a local (Winn) adoptive transfer assay, thus reinforcing the correlation between the DTH response and the antitumor protection.

The roles of two peritoneal T-lymphocyte populations in the in vivo rejection of methylcolanthrene-induced sarcoma.

Two phenotypically distinct T-lymphocyte populations infiltrating the peritoneal site of active tumor rejection were found to have specific reactivity against methylcolanthrene (MCA)-induced sarcoma(s) in two separate biological assays. One, expressing a Lyt 1+2- phenotype, mediates specific delayed type hypersensitivity (DTH) reaction to the immunizing MCA tumor transplantation antigen, and the other, expressing a Lyt 1+2+ phenotype, transfers in vivo protection against the MCA tumor in Winn assay. This latter antitumor immunity was specific for individually distinct transplantation antigens of each MCA sarcoma line. In contrast, standard transplantation tests by direct (whole animal) challenge demonstrated considerable tumor cross-reactivity. These findings and the relative contributions of the two T-cell populations are discussed in terms of effector mechanism.

Enhancement of tumor growth in mice: evidence for the involvement of host macrophages.

Intratumor host cells of methylcholanthrene-induced fibrosarcoma(s) were shown to enhance the in vivo outgrowth of syngeneic homologous tumors (MC1A, Mc2A, Mc2B) but not two heterologous T-lymphomas (EL4 and TLX9) in the Winn adoptive transfer assay. This enhancing activity was not restricted only to the latent period of tumor growth but was also observed during the period of active in vivo tumor proliferation. Tumor enhancement was mediated by a population of cells adherent to nylon wool and glass and insensitive to irradiation (with 850 rads) or to treatment with anti-Thy 1.2 serum and complement. Macrophages from peritoneal exudates of normal mice, used as control host cell population, showed similar tumor-enhancing activity. These findings suggest that tumor infiltrating host cells, predominantly macrophages appear to be the cell type responsible for tumor enhancement and active promotion of tumor growth (in vivo).