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Biomedical subjects

M K Wallack

Publications and source records attributed to M K Wallack.

At least 73 records · Page 4Linked to original sources

Effect of splenectomy on the growth of murine colon tumors.

We have previously demonstrated a high incidence of splenomegaly in BALB/c mice bearing colon tumor C-C36, but not colon tumor C-C26. To characterize this difference, tumor development in mice splenectomized seven days before tumor inoculation was compared to that of unoperated control mice. Our findings indicate that during the early phase, tumor growth is enhanced for both C-C26 and C-C36 in the splenectomized animals. The lag period for tumor appearance was also somewhat shorter in these splenectomized animals as compared to the controls, and metastatic tendency to the lungs was unaffected by splenectomy. These findings may have useful implications for the role of the spleen in the tumor-bearing animal.

Adenocarcinoma↗

Characterization of in vivo cross-reactive tumor resistance between two cultured murine colon lines.

Previous comparative investigations of the in vivo biology of two cultured colon tumors of BALB/c origin, C-C26 and C-C36, demonstrated different biologic activities. To elucidate these differences, the immunogenicity of these lines in providing protection to a subsequent challenge with different doses of tumor cells was investigated. Furthermore, the specificity of this protection was evaluated with cross-protection experiments. The findings demonstrate these lines to be immunogenic and suggest the presence of cross-reactive tumor rejection type antigens on these two cultured colon tumor lines. BALB/c mice immunized with these tumors developed resistance to challenge with the same tumor as well as to challenge with the other colon tumor line. Unexpectedly, BALB/c mice immunized with C-C26 cells and challenged with a syngeneic methylcholanthrene-induced sarcoma, Meth A, exhibited partial resistance to this tumor compared to nonimmunized controls. However, mice immunized with C-C36 cells and challenged with Meth A cells supported the same rate of growth of this tumor as unimmunized controls. These results suggest the presence of at least two different cross-reactive tumor rejection antigens. The first antigen appears to be shared between C-C26 and C-C36 cells while the second antigen may be shared between C-C26 and Meth A. Further definition of these putative antigens could provide us with a better understanding for the diagnosis and treatment of colon tumors.

Animals↗

Gestational carcinoma of the female breast.

Few neoplastic diseases can equal the amazing complexity and sheer perversity of carcinoma of the breast. No doubt as many decades of research lie ahead in its study as already have passed. Clinicians have long appreciated the special relationship of the disease to gestation. Diagnosis and treatment of breast cancer during pregnancy represent only a small part of this fascinating relationship. Although indispensable as research tools, animal models pertain to the human disease only in limited, ill-defined ways. The etiology of human breast cancer remains unclear; chemical, viral, hormonal, genetic, and immunologic theories have all been put forward as possibilities. Although gestation clearly alters both the initiation and growth of mammary tumors, its exact role in the various theoretical considerations remains a mystery. The obstetrician-gynecologist holds an important front-line position in the war against breast cancer, as does any provider of primary care to women, and, indeed, as do women themselves. Rather than decrease vigilance during pregnancy, the physician should pursue with extra vigor any breast mass discovered in the gravid patient, when the clinical examination is even less reliable than usual. The finding of a breast mass usually necessitates biopsy. Except for the inclusion of specific pregnancy-related problems, such as galactocele, the diagnostic spectrum of breast masses removed during pregnancy does not differ from that in nonpregnant women. The discovery of a highly suspicious breast mass, or the confirmed biopsy diagnosis of malignancy, in a pregnant patient should indicate the need for referral to a surgical oncologist versed in this unusual problem. The best approach to gestational breast cancer continues to be the team approach, with consultation from specialists in obstetrics, surgical oncology, anesthesiology, nuclear medicine, radiology, radiation oncology, pathology, and medical oncology. The age and general condition of the patient, the extent of the tumor, the stage of gestation, and the informed opinions of the patient and her spouse help to determine the therapeutic strategy. Careful staging not only guides present therapy but also the therapy of future victims through continued investigation. Most surgeons favor operation without delay if cure seems within reach. Mastectomy, with or without cesarean section, can be accomplished without detriment in the hands of a knowledgeable surgeon-anesthesiologist team. By following certain guidelines, the search for metastasis can be conducted safely and appropriately. The clinical situation occasionally may require the initiation of adjuvant radiotherapy or chemotherapy during pregnancy, by experienced consultants. Ongoing studies of tissue hormone receptors and cell kinetics will continue to give insight into the effects of gestational hormones on breast cancer and can aid in the selection of treatment options for the individual patient...

Abortion, Therapeutic↗

Transplantation immunity and cross-protection of two cultured murine colon lines.

Previous comparative investigations of the in vivo biology of two cultured colon tumors of BALB/c origin, C-C26 and C-C36, demonstrated different biologic activities. For elucidation of these differences, this report investigated the immunogenicity of these lines in providing protection to a subsequent challenge with different doses of tumor cells. Furthermore, the specificity of this protection was evaluated with cross-protection experiments. Our findings demonstrated these lines to be immunogenic and suggested the presence of cross-reactive tumor rejection-type antigens on these 2 cultured colon tumor lines. BALB/c mice immunized with these tumors developed resistance to challenge with the same tumor as well as to challenge with the other colon tumor lines. Further definition of these putative antigens could provide us with a better understanding for the diagnosis and treatment of colon tumors.

Animals↗

A preliminary trial of vaccinia oncolysates in the treatment of recurrent melanoma with serologic responses to the treatment.

A preliminary trial was designed as a toxicity/feasibility study using a fixed dose of vaccinia melanoma oncolysates (VMO) to treat recurrent stage II and stage III (skin, subcutaneous, and nodal metastases only) melanoma. There were no adverse consequences of the therapy, and 4 of the 12 patients treated seemed to have responded to the treatment by the criteria of the study. Sera from the six patients with the longest survival showed immunoreactivity to human melanoma lines in a Staphylococcus protein A assay (SpA) after 3 months of therapy. While the specificity of this immunoreactivity remains to be determined, the discovery of posttreatment serologic activity in a SpA assay permits investigation of the degree of VMO immunostimulation at different dose levels of the biologic. This assay may provide the means to quantitate optimal biologic dose for future melanoma oncolysate trials. The Southeastern Cancer Study Group is now conducting a phase I/II trial with these vaccinia melanoma oncolysates using the SpA assay to monitor this trial.

Antibodies, Neoplasm↗

Inflammatory oncotaxis after testing the skin of the cancer patient.

A case is presented in which a patient with Dukes C adenocarcinoma of the sigmoid colon subsequently developed a soft tissue metastasis at the site of a marked delayed type hypersensitivity response to the commonly used skin test antigen Dinitrochlorobenzene (DNCB). A possible cause and the implications of this rare occurrence are discussed. It is concluded that the inflammatory response to DNCB and the subsequent metastasis in this patient were causally related. Physicians who utilize skin testing in cancer patients should be aware of the possibility of "inflammatory oncotaxis" with the development of metastatic lesions in unusual places.

Adenocarcinoma↗

Cancer to the inguinal nodes from an unknown primary site.

Three cases of metastatic cancer to inguinal lymph nodes from unknown primaries are presented. All three patients had exhaustive workups which produced no primary lesions. There were two cases of metastatic squamous cell carcinoma and one of melanoma. A review of the literature shows that it is unusual to have metastatic disease without detectable primary lesions to the inguinal lymph nodes. Furthermore, and more importantly, these cases open discussion of recent concepts of tumor biology. Based on these newer concepts, suggestions are made concerning the examination and treatment of these unusual lesions.

Aged↗

Characterization of tumorigenicity, mortality, metastasis, and splenomegaly of two cultured murine colon lines.

The murine colon tumors 26 and 36 have been adapted to culture in vitro from the parental, serially transplanted tumors. The biological activities of these cultured colon lines (C-C26 and C-C36) have been characterized in vivo by s.c. inoculation of serial doses of cells into syngeneic BALB/c mice. The C-C26 line is highly tumorigenic and has a low tendency (9.1%) for metastasis to the lungs. Moreover, mice inoculated with C-C26 exhibited high mortality and normal or atrophied spleens. In contrast, the C-C36 line is less tumorigenic and highly metastatic to the lungs (77.8%). Mortality was lower in animals inoculated with C-C36, and at autopsy, splenomegaly was frequently (72.2%) observed without any visible metastatic nodules in these spleens. Metastasis to the lungs was intimately associated with splenomegaly, and death followed closely. Our findings with the C-C26 and C-C36 lines agree with those reported for the parental tumors with respect to tumorigenicity, tumor growth, and mortality. However, they differ with respect to their metastatic potential, because previous reports showed this to be higher for the serially transplanted colon 26 than the colon 36 tumor cells. Furthermore, this work describes the remarkable splenomegaly observed in mice inoculated with C-C36 but not with C-C26. This finding may in turn provide us with the opportunity to compare the functional status of the spleen in these tumor-bearing animals.

Animals↗

A new approach in the immunotherapy of carcinoma of the colon and rectum.

Although the therapy of carcinoma of the colon and rectum has been investigated, little progress has been made in prolonging the survival in these patients. Specific active immunotherapy may provide the answer. Previous investigators have shown that colorectal cancer elicits an immune response and may be susceptible to immunologic manipulation. My laboratory has shown that a live vaccinia virus-augmented (vaccinia oncolysate) tumor cell vaccine is safe and may be worthwhile in the surgical adjuvant treatment of colorectal cancer. Nine patients with advanced cancer were treated. 0/9 showed adverse effect and 3/9 showed lack of progression of disease. Randomized prospective trials are now underway.

Aged↗

[The treatment of advanced malignant melanoma with vaccina oncolysates (author's transl)].

Ten patients with recurrent stage II or III malignant melanoma received a live vaccinia virus augmented malignant melanoma cell vaccine. No patient had adverse reactions. The 3 patients surviving (10, 18 and 19 months) had: positive skin reactions to the vaccine (as they had previous positive skin reactions to common recall antigens), elevated vaccinia antibody titers, and they showed lack of progression of the disease with immunotherapy.

Antibodies, Neoplasm↗

Serum fucose as a monitor for recurrent malignancy.

Serum fucose determinations were performed on 19 patients with "stable" or "inactive" malignancies, 33 patients with "active" malignancies, and 14 "normals." A significant difference in the values between "normal" and "stable" patients and those with "active" cancer is shown. A role for this relatively simple serological test for diagnosing and following metastatic cancer is suggested.

Adult↗

A new approach in specific, active immunotherapy.

A vaccinia virus-lysed autochthonous tumor cell vaccine (vaccinia oncolysate) is introduced as a new specific, active immunotherapeutic agent against human cancer. Mouse experiments showed the vaccine to be a safe and potent immune mechanism stimulator. Human experimentation was undertaken in the knowledge of relative safety of the components of the vaccine, i.e. vaccinia vaccine and lysed, autochthonous tumor cells. Vaccine-treated patients had advanced metastatic cancer but reacted to one or more common recall antigen skin tests. None of the 13 patients had untoward responses; 7/13 patients had classic delayed hypersensitivity reactions at the vaccine injection sites; and 2/7 patients with injection site reactions had significant reduction in tumor burden. These results indicate that this vaccine is a specific, active immune mechanism stimulator, and may prove to be a useful therapeutic agent in the treatment of human cancer.

Animals↗

Perfusion therapy for extremity melanoma.

Because of their initial appearance on extremities, malignant melanomas lend themselves to isolated chemotherapeutic perfusions. Perfusion is attractive because one can deliver effective cytotoxic drugs without systemic toxicity. We are reviewing 20 patients treated between 1960 and 1973 with isolated perfusion. Melphalan (L-phenylalanine mustard) was the drug of choice. Eleven of the 20 patients had previous surgical treatment. Three of the 11 patients are still alive from 27 to 72 months postperfusion. Eight died after an average survival time of 33 months. Of the seven patients who underwent perfusion as primary therapy, four patients are alive from 25 to 76 months postperfusion, and three died after an average survival time of 34 months. There is direct correlation between stages and levels of melanoma, and perfusion and prolonged survival time.

Adult↗

Neuraminidase immunotherapy: serum potentiation of lymphocyte cytotoxicity related to immunoglobulin levels.

Seven patients completed couses of immunotherapy using neuraminidase-altered autochthonous cells. Their response to therapy was monitored by a cytotoxicity assay using 3H-proline-tagged tumor cells from the patient's own cultured tumor in a strictly autologous system. Serum effects were measured by exposing the tumor target cells to serum to see whether this impeded (blocked) or augmented (potentiated) lymphocyte cytotoxicity. Three of the seven patients developed increasing degrees of serum blocking effect and all died within six months of completing therapy. Four of the seven showed rapidly decreasing blocking and three eventual potentiation. Three patients are living, improved, and free of evidence of tumor. There was an increase in average serum immunoglobulins in patients developing potentiation, and a decrease in those showing blocking. In any immunotherapy program attention must be given to in vitro monitoring studies, and such studies should include attention to the serum factors influencing host response.

Adult↗