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Biomedical subjects

R Lafreniere

Publications and source records attributed to R Lafreniere.

At least 37 records · Page 2Linked to original sources
PubMed1989

Ocular melanoma in Alberta: a 38 year review pointing to the importance of tumor size and tumor histology as predictors of survival.

A large number of cases of ocular melanoma have been entered in The Provincial Cancer Registry of Alberta over the past 40 years. This study was undertaken in order to describe further the natural history of this disease and derive management recommendations for use at the provincial level. A retrospective chart review was carried out on all cases of ocular melanoma registered through The Alberta Provincial Cancer Registry between 1949 and 1987. Two hundred fifty-one cases were identified: 143 were males and 108 were females. The mean age of the patients at diagnosis was 60. The majority of the melanomas arose from the choroid of the eye (82%) with the remainder arising from the iris, conjunctiva and ciliary body, respectively. According to the Callender classification for ocular melanomas, the majority of the melanomas were of the spindle cell type (53%), the others being either mixed cell (23%), epithelioid (8%), or fascicular (1%). Survival rates differed depending on the cell type. Spindle cell tumors demonstrated a mean survival time of 5.2 years; epithelioid tumors 4.8 years and the mixed cell tumors appeared to be the most aggressive with a mean survival time of 2.7 years after diagnosis. The majority of deaths from ocular melanoma occurred within 5 years of diagnosis, although 14% of patients in this review presented with metastases more than 10 years after diagnosis. Some of the cases of ocular melanoma could be classified pathologically as small, medium, or large. Patients with large ocular melanomas had a 5 year survival rate of 33% compared to 70% and 66% for patients with small and medium sized tumors. Of note, 43% of patients with large ocular melanomas who were dead from their disease within 5 years of diagnosis were also found to have mixed cell tumors. These findings call for a longer follow-up period for ocular melanomas and point to the importance of cell type and tumor size as predictors of survival and as guides in planning prophylactic therapeutic interventions.

Alberta↗
PubMed1989

Induction of cytotoxicity from fresh splenocytes after in vivo administration of cyclophosphamide. Importance of long-term culture with high-dose recombinant interleukin-2.

Cyclophosphamide, combined with lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2), is known to mediate regression of tumors, but the effects of cyclophosphamide on the subsequent generation of LAK cells are unclear. It was the aim of the experiments in this paper to determine whether fresh splenocytes cultured with rIL-2 would maintain or regain their cytotoxicity in vitro after being exposed to the cytotoxic agent cyclophosphamide in vivo. Functional monitoring of splenocytes after in vitro incubation with rIL-2 was performed at various times through chromium-release assays, thymidine assays and cell-cycle analysis. Chromium-release assays determined that the cytotoxicity of cultured splenocytes returned to normal after 12 days of in vitro culture with rIL-2. The thymidine assays indicated a normal rate of uptake of thymidine after 7 days in culture, while the cell cycle was still abnormal by day 12 of culture. The growth and expansion of rIL-2-activated splenocytes after different times of in vitro culture indicated a return to normal compared to control animals after 7 days of continuous in vitro exposure to rIL-2. It is concluded that murine splenocytes can demonstrate cytotoxicity after exposure to cyclophosphamide, through prolonged continuous in vitro culture with rIL-2. Since cyclophosphamide did not jeopardize the production of splenocyte cytotoxic effectors generated with rIL-2, it appears to be a strong contender for use in chemoimmunotherapy protocols.

Animals↗
PubMed1989

Tumor-infiltrating lymphocytes cultured in recombinant interleukin-2: enhancement of growth, cytotoxicity, and phenotypic expression of cytotoxic T-cell antigens by cyclophosphamide given intravenously prior to tumor harvest.

Tumor-infiltrating lymphocytes (TILs) have potent antitumor effects in murine models of advanced disease. Although these cells are 50-100 times more potent than lymphokine-activated killer cells against micrometastases, their antitumor benefits are virtually nonexistent against large tumor burdens unless cyclophosphamide is added to the immunotherapy regimen. In an effort to determine the effects of cyclophosphamide on TILs obtained from tumor-bearing animals, we harvested tumors from animals having received either 0, 50, or 100 mg/kg cyclophosphamide intravenously and investigated the expansion, cytotoxicity, and phenotypic expression of these TILs co-cultured in vitro with recombinant interleukin-2. TILs obtained from animals given cyclophosphamide, demonstrated a greater fold expansion than TILs obtained from normal animals (mean fold expansion on day 59 of culture: 85, 400, and 150 for TILs obtained from animals given 0, 50, and 100 mg/kg cyclophosphamide, n = 3 consecutive experiments). In addition, these TILs demonstrated enhanced cytotoxicity compared to controls [effector to target ratio 4:1, day 16 TILs, % lysis: 24, 35, and 45%, cyclophosphamide 0, 50, and 100 mg/kg, respectively, against the MCA-102 sarcoma, natural killer (NK) insensitive tumor; 29, 38, and 56% against the YAC-1 lymphoma, NK sensitive tumor]. Similar results were seen with day 34 and day 59 TILs. When phenotypic analysis was performed, TILs obtained from animals given cyclophosphamide consistently demonstrated a greater percent expression of the Thy1.2 and Lyt-2 antigens up to day 59 of culture when the experiments were terminated. The NK cell marker 49H.8 was expressed on the majority of TILs and its expression did not change with respect to the cyclophosphamide concentration. The increase in TIL number and cytotoxicity seen with cyclophosphamide given intravenously before tumor harvest could have important ramifications for human immunotherapy with TILs.

Animals↗
PubMed1988

Antitumor effect of recombinant tumor necrosis factor-alpha against murine sarcomas at visceral sites: tumor size influences the response to therapy.

We examined the antitumor efficacy of rTNF-alpha administration on established tumor at two visceral sites, lungs and liver. Treatment of B6 mice harboring multiple (greater than 100 foci of less than or equal to 0.5 mm diameter) 10-day pulmonary macrometastases from the MCA-106 sarcoma, with dosages of rTNF-alpha (5-10 micrograms, single dose i.v.) that caused hemorrhagic necrosis and regression of a 6 mm MCA-106 s.c. tumor, had no impact on the number (or size) of lung nodules. Similarly, rTNF-alpha failed to show an antitumor effect in B6 mice with advanced day 8 or 10 multiple (greater than 100 foci of less than or equal to 0.5 mm diameter) hepatic metastases at single i.v. doses up to 20 micrograms, as measured by either enumeration of residual liver nodules or survival. B6 mice injected s.c. with MCA-106 sarcoma and treated with rTNF-alpha as a single i.v. dose on day 0, 3, 5, or 7 experienced marked tumor regression only after the day 7 rTNF-alpha injection, when the tumor had achieved a size of 5-6 mm in diameter. Since tumor size appeared important for rTNF-alpha susceptibility in vivo, we next induced a single hepatic tumor of the MCA-106 sarcoma by the direct injection of cells into the left lobe of the liver and treated these mice at day 10 when the nodule had achieved a size of 5-6 mm in diameter. Increasing doses of rTNF-alpha (up to 8 micrograms) given as a single i.v. injection resulted in increasingly greater reductions in hepatic tumor as well as significant survival benefit of the treated mice. Sites of regressing hepatic tumor exhibited central necrosis accompanied by polymorphonuclear leukocytes and lymphocytes. Collectively, these results show that rTNF-alpha administration can mediate a significant antitumor effect on visceral tumor and suggest that tumor size is an important factor in rTNF-alpha susceptibility not only for tumors growing at s.c. sites but also for those established at visceral sites.

Animals↗
PubMed1988

Punch biopsy for diagnosis of pigmented skin lesions.

Melanoma is a potentially fatal cancer with a relatively high incidence, but it can be cured if the lesions are removed at an early stage. Punch biopsy is a cosmetically acceptable, rapid method for removing small pigmented lesions to allow definitive pathologic diagnosis. The technique, which usually requires only a small amount of local anesthetic and no sutures, can be performed by a busy physician at the time the suspicious lesion is discovered.

Biopsy↗
PubMed1987

Effect of anti-B16 melanoma monoclonal antibody on established murine B16 melanoma liver metastases.

The administration of anti-B16 monoclonal antibody of the IgG2b isotype to mice bearing established B16 melanoma liver metastases caused a significant and consistent reduction of up to 90% in the number of these metastases. No reduction in the number of metastases was noted when antigenically unrelated tumor or nonspecific immunoglobulin were employed. The antibody-mediated antitumor effect was completely abrogated by total body irradiation of the host. Treatment of the tumor-bearing host with antiserum directed against asialo GM1 prior to anti B16 antibody administration, abrogated the therapeutic effect indicating the involvement of a radiosensitive, ASGM1-positive cell in the tumor regression. The antitumor effect of the antibody treatment could be augmented by the concomitant administration of recombinant interleukin-2. The effect seen may have possible application in the treatment of liver metastases in humans by combined immunotherapy using recombinant interleukin-2 and specific antitumor monoclonal antibodies.

Animals↗
PubMed1987

Breast carcinoma post-augmentation mammaplasty: therapy with limited surgery and radiation.

Due to the recent surgical and technical developments in aesthetic surgery and occasional dissatisfaction of women with their external contour, augmentation mammaplasty has become a common occurrence in the surgical practice of the aesthetic surgeon. Breast carcinomas, incidentally associated with augmentation mammaplasty, have been sporadically reported in the literature and have all been treated with a mastectomy when resection was possible. We present a case of breast carcinoma occurring 5 years after augmentation mammaplasty performed with silicone-gel-filled implants. Therapy of this carcinoma was achieved through a segmental mastectomy followed by postoperative radiation. The patient remains well 15 months postoperatively. A large number of breast implants are performed each year and the likelihood of a higher incidence of incidental breast carcinomas seen with implants is certainly possible as these patients become older; thought should be given to the notion that possibly not all of these cases need to be managed with radical surgery.

Adult↗
PubMed1987

Phlegmonous duodenitis complicating multiple myeloma: a successfully treated case.

A patient receiving chemotherapy for multiple myeloma suddenly developed an acute abdomen, fever, and neutrophil leukocytosis. At laparotomy, the distal two-thirds of the duodenum was swollen and hemorrhagic and was surgically excised. The specimen displayed an acute phlegmonous (suppurative) duodenitis with submucosal and transmural acute inflammation and edema despite an intact mucosa. Blood cultures grew Group B, beta-hemolytic streptococci and gram-positive cocci were present histologically. The patient recovered uneventfully following the surgery and a course of broad spectrum antibiotic therapy. This case illustrates that localized suppurative intestinal infection should be considered when immunosuppressed patients present with an acute abdomen, and that aggressive surgical and antibiotic therapy is warranted.

Cellulitis↗
PubMed1986

Optimal methods for generating expanded lymphokine activated killer cells capable of reducing established murine tumors in vivo.

The systemic administration of lymphokine activated killer (LAK) cells and recombinant interleukin-2 (RIL-2) is effective in reducing the number of established pulmonary and hepatic metastases from multiple murine tumors and has recently been shown to be effective in mediating the regression of metastatic cancer in humans as well. The generation of sufficient numbers of LAK cells for the effective therapy of human tumors remains a major obstacle to the widespread application of this immunotherapeutic approach. We have thus studied methods for the in vitro expansion of LAK cells effective in immunotherapy. Our previous studies used LAK cells generated in culture with RIL-2 for 3 days. LAK cells cultured in RIL-2 for 5 or 7 days were not significantly different from cells cultured for 3 days either in the number of cells obtained, their in vivo cytotoxicity or their in vivo therapeutic effectiveness. When day 3 LAK cells were transferred to fresh culture medium containing 1000 U/ml of RIL-2, a highly reproducible expansion of these cells was obtained. By day 5, cell numbers expanded 9.6 +/- 0.8-fold (mean +/- SEM; n = 36) and by day 8, cells expanded 15.1 +/- 1.0-fold (n = 19). In 4 h 51Cr release assays against fresh tumor target cells, day 3 LAK cells had a mean of 13 lytic units/10(6) cells in 24 experiments. Day 5 expanded LAK cells had a mean of 30 lytic units/10(6) cells in 13 experiments (P less than 0.05 compared to day 3 LAK cells) and day 8 expanded LAK cells had a mean of 11 lytic units/10(6) cells in 6 experiments (P = NS compared to day 3 LAK cells) When day 5 and day 8 expanded LAK cells were infused in vivo with RIL-2, they were found to significantly reduce the number of experimentally induced pulmonary metastases as effectively as non-expanded conventional day 3 LAK cells. Similar findings were documented in experiments against hepatic metastases. These experiments demonstrate that LAK cells could expand a mean of 15-fold in vitro in RIL-2 and maintain their anti-tumor therapeutic effectiveness when adoptively transferred. These experiments suggest methods for generating increased numbers of cells for use in the adoptive immunotherapy of human cancers and may substantially reduce the need for repeated leukophereses of cancer patients undergoing this therapy.

Animals↗
PubMed1986

A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes.

The adoptive transfer of tumor-infiltrating lymphocytes (TIL) expanded in interleukin-2 (IL-2) to mice bearing micrometastases from various types of tumors showed that TIL are 50 to 100 times more effective in their therapeutic potency than are lymphokine-activated killer (LAK) cells. Therefore the use of TIL was explored for the treatment of mice with large pulmonary and hepatic metastatic tumors that do not respond to LAK cell therapy. Although treatment of animals with TIL alone or cyclophosphamide alone had little impact, these two modalities together mediated the elimination of large metastatic cancer deposits in the liver and lung. The combination of TIL and cyclophosphamide was further potentiated by the simultaneous administration of IL-2. With the combination of cyclophosphamide, TIL, and IL-2, 100% of mice (n = 12) bearing the MC-38 colon adenocarcinoma were cured of advanced hepatic metastases, and up to 50% of mice were cured of advanced pulmonary metastases. Techniques have been developed to isolate TIL from human tumors. These experiments provide a rationale for the use of TIL in the treatment of humans with advanced cancer.

Adenocarcinoma↗
PubMed1986

Pure squamous cell carcinoma of the breast.

Pathological curiosities have always fascinated the surgical community, and management of breast cancer by the physician has, at times, revealed such rarities. A recent case of squamous cell carcinoma in a clear fluid breast cyst has prompted a review of our experience with this rare pathology, and allowed us to make the following statements: We propose that squamous cell carcinoma of the breast arises from ductal metaplasia. When the T.N.M. system is applied to the squamous cell lesion, the apparent poor prognosis that it is believed to carry may not be so apparent. If no other primaries are identified after extensive metastatic work-up, surgical therapy consisting of total mastectomy with complete axillary dissection, is very effective in local control of tumor progress. Nodal status will indicate the need for additional modalities of therapy.

Breast Neoplasms↗
PubMed1986

Squamous cell carcinoma of the rectum: a multimodality approach.

A 60-year-old homosexual male with a diagnosis of squamous cell carcinoma of the rectum, arising 7 cm from the dentate line, was treated with a rectal preserving multimodality approach consisting of excisional biopsy and chemotherapy with 5-fluorouracil (5-FU) and mitomycin-C with concomitant administration of radiation therapy to the tumor and pelvic nodal bearing areas. The patient has remained disease-free with full preservation of anorectal function on follow-up at 2 years. This approach to a difficult and unusual problem is recommended as a first line of therapy rather than surgical resection if it is deemed that the patient can tolerate a combination of chemo and radiation therapy and the patient will be able to participate in a long-term follow-up.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Differences in the effects of host suppression on the adoptive immunotherapy of subcutaneous and visceral tumors.

A syngeneic transplantable sarcoma induced in C57BL/6 mice, MCA 105, was used in studies to examine host suppression on the adoptive immunotherapy of established intradermal and experimentally induced pulmonary and hepatic metastases. Fresh immune splenocytes were generated from mice immunized to the MCA 105 tumor by a mixture of viable tumor cells and Corynebacterium parvum. The adoptive immunotherapy of intradermal MCA 105 tumor with immune cells required prior immunosuppression of the recipient by sublethal irradiation with 500 R or T-cell depletion. The effect of whole-body sublethal irradiation appeared to eliminate a systemic host suppression mechanism, since partialbody irradiation involving the tumor-bearing area did not permit successful immunotherapy. Host irradiation was not required to achieve successful immunotherapy of experimentally induced pulmonary or hepatic metastases. In nonirradiated recipients bearing both intradermal and pulmonary tumors, host suppression did not affect the function of transferred immune cells to induce regression of pulmonary metastases. Thus, suppression of adoptive immunotherapy appears to be relevant to tumors confined to the skin and subcutaneous tissue but not to tumor in visceral sites, such as the lung and liver.

Animals↗
PubMed1986

A novel approach to the generation and identification of experimental hepatic metastases in a murine model.

A reproducible model for the selective generation of liver metastases has been developed. The spleen is exteriorized by means of a small subcostal incision and is directly injected with a 1-ml suspension of tumor cells. Tumor cells flow out of the splenic vein into the portal vein and lodge in the liver. Splenectomy is performed approximately 1 minute after tumor cell injection. The procedure is simple, requires a single operative procedure, and is applicable to a wide variety of tumors. Over a 6-month period, more than 3,000 such procedures with the use of 5 different tumors were performed in C57BL/6 mice, resulting in a 1.9% mortality. For reliable enumeration of the number of hepatic metastatic deposits, a suspension of india ink was injected iv, and the liver was removed and bleached with Fekete's solution. Tumor nodules appeared as discrete white nodules against the black background of normal liver parenchyma. This model provides a useful tool for the study of the experimental therapy of hepatic metastases in mice.

Adenocarcinoma↗
PubMed1986

Effect of immunotherapy with allogeneic lymphokine-activated killer cells and recombinant interleukin 2 on established pulmonary and hepatic metastases in mice.

The adoptive transfer of lymphokine-activated killer (LAK) cells in conjunction with the systemic administration of recombinant interleukin 2 (RIL-2) results in the regression of established pulmonary and hepatic micrometastases from a variety of immunogenic and nonimmunogenic murine tumors in syngeneic C57BL/6 mice. Recent studies have shown that this therapeutic approach can mediate the regression of cancer in humans as well. Because of the practical difficulties in obtaining syngeneic or autologous LAK cells for the therapy of cancer in humans we have now evaluated the antitumor efficacy of allogeneic LAK cells generated from different strains of mice. The in vitro lysis of fresh tumor targets by LAK cells is not a major histocompatibility complex-restricted phenomenon since LAK cells of BALB/c-H-2d, DBA/2-H-2d, and C3H-H-2k origin all exhibited lytic activity when tested against allogeneic MCA-102-H-2b tumor cells in short term 51Cr release assays. In vivo, the i.v. transfer of allogeneic LAK cells combined with i.p. injections of RIL-2 reduced the number of established pulmonary metastases induced by either MCA-105 or MCA-101 tumors which are syngeneic to C57BL/6 hosts. The extent of reduction of these pulmonary metastases by the allogeneic LAK cells was directly dependent upon the dose of RIL-2 given; increasing doses of systemically administered RIL-2 resulted in increasingly greater reduction in the numbers of established 3-day pulmonary sarcoma metastases. In dose titration experiments, adoptive transfer of at least 2 doses of 10(8) allogeneic LAK cells was necessary to achieve significant antitumor effect in vivo. Allogeneic LAK cells were also successful in mediating significant regression of hepatic micrometastases. Again, the i.v. transfer of allogeneic LAK cells had a smaller therapeutic benefit compared to i.v. transfer of syngeneic LAK cells. When allogeneic LAK cells were injected intraportally, however, they were as effective as syngeneic LAK cells. Allogeneic LAK cells had little, if any, therapeutic effect on established pulmonary and hepatic metastases when administered to recipients previously immunized to the histocompatibility antigens on the donor cells. Taken together, our results indicate that allogeneic LAK cells from several strains of mice are effective in lysing fresh MCA-102 tumor in vitro and that when given i.v. in sufficient numbers, in conjunction with RIL-2, they can mediate significant reduction in the number of established pulmonary and hepatic micrometastases in nonalloimmunized C57BL/6 mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Infrared light scanning of the breast.

Transillumination and Infrared Light Scanning (I.L.S.) of the breast were evaluated in a high referral breast clinic over a 15-month period. Seven hundred (700) patients were examined and blindly transilluminated; 101 were biopsied, all had mammography. The study was conducted in two phases: Phase I evaluated transillumination without I.L.S. This included 22 biopsied patients out of 101, with eight carcinomas identified histologically, demonstrating 87 per cent sensitivity and 64 per cent specificity for transillumination, versus 87 per cent and 71 per cent for mammography, and 87 per cent and 57 per cent for examination. Phase II evaluated simple transillumination combined with I.L.S. This included 79 biopsied patients out of 101 with 26 carcinomas identified histologically, demonstrating 96 per cent sensitivity and 74 per cent specificity for transillumination combined with I.L.S. compared to 85 per cent and 72 per cent for mammography and 81 per cent and 73 per cent for examination. Of the 26 Phase II carcinomas identified, two were not felt by examination, and two were neither felt nor read correctly by mammography. I.L.S. of the breast has proven effective in the hands of trained personnel and should be used with routine breast examination or mammography to increase yield of breast pathology.

Adult↗
PubMed1985

Hartmann's pouch carcinoma.

Since 1921, when Henry Hartmann first described his procedure for rectal carcinoma, multiple modifications of the original technique have been proposed. However, the basic principle of a rectal pouch has always been retained. Two cases of carcinoma developing in such a pouch are described; both occurred years after creation of the pouch. One was managed by local resection through a transsacral approach; the other required an abdominoperineal resection. Consideration must be given to careful examination and sigmoidoscopy of these pouches as they tend to be forgotten by the physicians due to their hidden location.

Adenocarcinoma↗