Satya M. Murthy

The influence of surgical trauma on experimental metastasis

Influence of surgical trauma on experimental metastasis in healing wounds is investigated using a transplantable murine mammary carcinoma cell line, TA3Ha. Intravenous injection of 105, 106, and 2 × 106 TA3Ha cells into syngeneic Strain A mice led to liver or kidney tumor development in none of the 96, ten, and ten mice tested, respectively. In contrast, injection of 105 cells into mice immediately after hepatic wedge resection performed using milliwatt carbon dioxide laser and electrocautery resulted in tumor formation at the site of trauma in 21/37 (57%) and 25/52 (48%) mice, (P < 0.001) respectively. Similar results were obtained in mice subjected to partial nephrectomy using the laser (nine of 18) and electrocautery (eight of 13). These results clearly demonstrate that surgical trauma renders a nonprivileged organ susceptible to experimental metastasis formation, and that at least in this model both laser and electrocautery have similar effects. Tumor cell injection 1, 7, and 10 days posthepatic surgery resulted in 36%, 20%, and 0% tumor formation, respectively, indicating that the earlier events in wound healing support tumor implantation and/or growth better than those later on. Frequency of tumor formation at sites of trauma in the peritoneum induced by scalpel blade, laser, and electrocautery were 28%, 50% and 82%, respectively. Peritoneal tumors were seen in 33% of the nonsurgical mice. Skin incisions induced with the three above probes had little influence on experimental metastasis formation. Thus the influence of trauma on tumor formation is not uniform in every organ.

Tn, a carcinoma-associated antigen, reacts with anti-Tn of normal human sera

Tn antigen is the immediate precursor of the carcinoma (CA)‐associated T antigen; both are masked in non‐CA tissues. Tn antigen was detected by absorption of human anti‐Tn antibody in 46 of 50 primary breast CAs and in all 6 metastases originating from Tn‐positive primary CAs. Thirteen of 25 (52%) anaplastic CAs, but only 2 of 15 (13%) well differentiated CAs had more Tn than T; 1 anaplastic CA had neither antigen. Eighteen of 20 benign breast lesions had no Tn; the 2 positive lesions were premalignant. All 19 breast CAs, studied immunohistochemically, reacted strongly with human polyclonal anti‐Tn; benign or normal glandular tissues had minimal or no reactivity. Among live cancer cell lines, the most malignant sublines had more Tn than T on their cell surfaces. Preliminary studies with rodent monoclonal anti‐Tn and anti‐T antibodies gave immunohistochemical reactivity patterns similar to those of the polyclonal antibodies, but the former were less sensitive in absorption tests. Tn is a CA marker that promises to be useful in tumor detection.

Patients' immune response to breast and lung carcinoma-associated thomsen-friedenreich (T) specificity

SummaryWe report here sensitive and specific measurement of immune responses of patients with certain kinds of carcinoma toward the physically and chemically well defined T antigen isolated from healthy human erythrocytes. Over 90% of adenocarcinoma tissues tested possess T-specific immunoreactive structures as determined withhuman antisera, in contrast to healthy tissues and benign lesions. Adenocarcinoma patients recognize the carcinoma-associated T antigen as foreign. Delayed-type skin hypersensitivity reaction to T antigen (DTHR-T) was positive in all 25 lung adenocarcinoma patients tested, in 88% of 101 patients with ductal, in 43% of 30 patients with lobular or tubular breast carcinoma and in 9/9 patients with adenocarcinoma of body cavities. Patients of all Stages reacted positively. All 7 patients with small cell lung carcinoma and 3/5 with malignant melanoma had a positive DTHR-T. None of 17 patients with malignant brain tumors, leukemia or Hodgkins disease, sarcoma or thyroid carcinoma reacted. The DTHR-T was specific in that all 77 healthy persons and 48/49 with other diseases, including 23/24 with non-cancer lung disease were negative; one patient with organizing interstitial pneumonitis was positive. This points to a possible source of false positive reactions. 91% of 149 patients with histologically benign breast disease had a negative DTHR-T; the histology of some of the positive ones was reexamined, 2 proved to have carcinoma in situ. In vitro leukocyte migration inhibition and scoring of anti-T hemagglutinin titer using the T-anti-T system diagnosed many adenocarcinomata correctly, including 4 whose histology, while turning positive later, was negative at the time. However, these tests were generally less sensitive and specific than the DTHR-T.This system may also be of screening and monitoring value. Surgical removal of primary carcinoma led to a rebound of anti-T in breast carcinoma patients and its renewed decrease in some, prior to clinical recurrence of cancer. Also, the DTHR-T turned from positive to negative in some Stages I and II breast-and T1–2 N0–1 M0 lung adenocarcinoma patients who had no demonstrable relapse during the ensuing observation period.ZusammenfassungWir berichten hier über sensitive und spezifische Bestimmung der Immunatwort von Patienten mit Brust- und Lungenadenokarzinom gegen das physikalisch und chemische definierte T Antigen, isoliert von menschlichen Erythrozyten. Über 90% der untersuchten Adenokarzinomgewebe besaßen T-spezifische immunreactive Strukturen, gemessen mithuman-anti-T Seren, im Gegensatz zu gesunden und gutartig veränderten Geweben. Bei Adenokarzinomträgern wird das karzinom-assoziierte T Antigen vom Organismus als fremd erkannt. Die verzögerte Hautüberempfindlichkeitsreaktion gegen T Antigen (DTHR-T) war in allen 25 Patienten mit Lungenadenokarzinom positiv, in 88% von 101 Patienten mit ductulärem, in 43% von 30 mit lobulärem oder tubulärem Mammakarzinom sowie in 9/9 Patienten mit Körperhöhlen-Adenokarzinomen. Alle 7 Patienten mit kleinzelligem Lungenkarzinom und 3/5 mit malignem Melanom reagierten positiv. Die DTHR-T war negativ in allen 17 Patienten mit malignen Hirntumoren, Leukämien, Hodgkin, Sarkom und Schilddrüsenkrebs. Die DTHR-T war spezifisch: alle 77 gesunden und 48/49 Personen mit nichtkrebsigen Erkrankungen einschließlich 23/24 Lungenpatienten hatten eine negative DTHR-T; ein Patient mit organisierender interstitieller Pneumonitis reagierte positiv; dies deutet auf eine mögliche Fehlerquelle hin. 91% von 149 Patienten, histologisch als gutartige Brusterkrankung diagnostiziert, hatten eine negative DTHR-T; die Histologie einiger positiv reagierender Patienten wurde reexaminiert und erwies sich in 2 Fällen als in situ Karzinom.In vitro „Leukocyte migration inhibition“ und „scoring“ der anti-T Agglutinine ergaben eine korrekte Diagnose bei vielen Adenokarzinomen einschließlich 4 Fällen, die zur Zeit unserer positiven Resultate eine negative Histologie hatten, bei denen spätere Biopsien aber positiv ausfielen. Im allgemeinen waren die in vitro Teste weniger sensitiv und spezifisch als die DTHR-T.Das T-anti-T System könnte sich auch zum „screening“ und „monitoring“ eignen. Chirurgische Entfernung des Primärkarzinoms führte zu einem „rebound“ des anti-T Titers in Brustkrebspatienten, erneuter Abfall wurde in einigen Fällen vor klinischem Rückfall beobachtet. Positive DTHR-T wurde wieder negativ in mehreren Fällen von Brustkrebs Stage I und II bzw. Lungenadenokarzinom T1–2 N0–1 M0; diese Patienten hatten in der folgenden Beobachtungszeit keinen klinischen Rückfall.

Tyrosine kinase inhibitors as antiproliferative agents against an estrogen‐dependent breast cancer cell line in vitro

Receptor tyrosine kinase (RTK) activation is critical for growth factor‐mediated cell proliferation. Blockade of RTK activation inhibits growth factor‐induced cell proliferation. A panel of RTK inhibitors (tyrphostins) have been tested and compared for their antiproliferative effects on the hormone‐dependent human breast cancer cell line, MCF‐7, in vitro.

Perioperative stimulation of residual cancer cells promotes local and distant recurrence of breast cancer

In vivo animal research (1-3) has demons t ra ted that cancer cells can have a dramatic and clinically significant interact ion with a fresh surgical wound. We have demons t ra t ed that circulating carc inoma cells can be di rected to a site that was historically refractory for that cancer by surgically injuring that site just before the intravenous injection of carc inoma cells. We have demons t ra ted that tum o r cells would implant and grow at a surgically injured liver, spleen, cecum, bone, or kidney in 50 to 75% of animals compared with essentially no metastatic rate to these sites in an un in ju red animal (1, 4, 5). The cancer cells would be attracted not just to the in jured organ, but to exactly the in jured site. Fur thermore , the injured area t ended to be the single site of greatest tumor b u r d e n of all metastatic foci. Fisher and colleagues have shown that factors locally released by the surgical resection of a carc inoma can stimulate cancer cells at a distant site (6, 7). This interact ion between cancer cells and the surgical wound env i ronment has impor tan t implications on results of surgical therapy of malignancies. The attraction to and stimulation of mal ignant ceils by the growth substances released f rom the surgical wound are felt to be a major obstacle to our ability to cure cancer by surgery alone. To ascertain whe the r the surgical extirpation of breast cancer facilitates local and distant tumor

Precursors of the Blood Group NM Antigens Are Human Carcinoma-Associated

Publisher Summary This chapter explains the relationship of the precursors of the blood group NM antigens with human carcinoma. The Thomsen–Friedenreich (T) antigen is a direct precursor in the biosynthesis of the human N & M blood group. The immediate precursor of T antigen is the Tn antigen. Both antigens do not occur in reactive form in healthy humans. The T & Tn specificities are associated with breast carcinomata and also with those of gastrointestinal tract. In a study described in the chapter, the patients with breast carcinoma and persons without carcinoma showed shrinking cell mediated immunity to T antigen but not to NM antigens. The chapter discusses the way to enhance the immune system of patents of breast carcinoma of stage 2 and 3. It also discusses the diagnostic and therapeutic implications. It presents the percent absorption of anti-blood group m, n, and precursor agglutinins with human breast gland membrane-cytoplasm preparations and gastrointestinal carcinomata. The T antigen is a direct precursor in the biosynthesis of the human N and M blood group-specific immunodeterminant structures, which are synthesized by sialyltransferases.