Claus Gropp

Ectopic hormones in lung cancer patients at diagnosis and during therapy

In roughly 110 patients with lung cancer of various histologic types, the levels of hormones adrenocorticotropin (ACTH), calcitonin, parathormone, beta‐choriogonadotropin (HCG), human placental lactogen (HPL), growth hormone (HGH), and prolactin were determined by radioimmunoassay. The ACTH level was elevated in 30% of patients with oat cell carcinoma and in 26% of patients with large cell carcinoma. Calcitonin levels were increased in 48% of patients with oat cell carcinoma. Elevated levels of HCG were found in 33% of patients with oat cell carcinoma, in 26% of patients with large cell carcinoma, and in 19% of patients with squamous cell carcinoma. Parathormone was increased in 32% of patients with squamous cell carcinoma, in 27% of patients with oat cell carcinoma, and in a few patients with large cell carcinoma. Prolactin, HCG and HPL were present only in single cases. Elevated levels of at least one hormone were found in 65.2% of all patients, and in 78% of the patients with oat cell carcinoma. Serial determinations of ACTH and calcitonin showed that these hormones are useful for monitoring therapy in lung patients. There was no relation between hormone levels and the clinical stage of disease.

Establishment, growth properties, and morphological characteristics of permanent human small cell lung cancer cell lines

SummaryCell lines from SCLC were established with a success rate of 43% from different metastatic sites of treated and untreated patients. All 6 SCLC cell lines grew as floating cell aggregates without substrate adherence. The degree of aggregation ranged from very tight spheroids to very loose sheets and chains. This gross morphological property showed a striking correlation to the PDT, with short PDTs in loose growing cell lines and long PDTs in tight growing cell lines. Cell size and nuclear features, i.e., chromatin pattern and nucleolar prominence, also seemed to correlate with the PDT and gross morphology. All SCLC cell lines had dense core granules by electron microscopical examination. Several different serum-free and serum-supplemented growth media were tested for their feasibility in estabilishing and permanently growing SCLC. Serum-free SIT medium and SIT 2.5 medium provided the best results in liquid culture. For semisolid SCLC cultivation, R10 medium was suprior to all other media tested. These cell lines are currently under intensive biochemical, molecular biological, and cytogenetical investigation in different laboratories and thus provide a tool for studying the biology of lung cancer.

Carcinoembryonic antigen and ferritin in patients with lung cancer before and during therapy.

Carcinoembryonic antigen (CEA) levels were determined in 114 patients with confirmed lung cancer at the time of diagnosis using the CEA Ire‐Sorin radioimmunoassay. Elevated CEA values were found in 47%. Most of the patients with high CEA levels had clinically detectable metastases. Ferritin was detectable by the Laurell‐electrophoresis in the serum of 58 out of 81 (72%) of the patients with confirmed lung cancer at the time of diagnosis. Ferritin levels were significantly higher in patients with metastases. Serial measurements of CEA and ferritin during radio‐ and chemotherapy showed that the assay may be useful to evaluate the effects of therapy. Because of some false negative results both CEA and ferritin determinations should be used only in context with other clinical and laboratory findings. Cancer 42:2802–2808, 1978.

Alternating versus sequential chemotherapy in small cell lung cancer. A randomized german multicenter trial

A total of 306 patients with small cell lung cancer (SCLC) were randomized to receive chemotherapy in a sequential or alternating mode. Sequential chemotherapy consisted of eight cycles of cyclophosphamide, Adriamycin (doxorubicin), and vincristine (CAV) and alternating chemotherapy consisted of three cycles (1, 3, 5) of etoposide, vindesine, and ifosfamide (EVI); three cycles (2, 4, 6) of cisplatin, Adriamycin, and vincristine (PAV); and two cycles (7, 8) of cyclophosphamide, methotrexate, and CCNU (CMC). Responsive patients received prophylactic cranial irradiation after three cycles and chest irradiation after eight cycles of chemotherapy. No maintenance therapy was applied to patients achieving complete remission. Minimum follow‐up was 2 years. Of the 302 patients evaluable, overall response rate was 59% in the sequential arm and 70% in the alternating arm. Patients treated with CAV had a complete response rate of 21% in contrast to 36% for those receiving alternating therapy. The median survival for all patients was 9.8 versus 11.3 months, for limited disease 11.1 versus 13.4 months, and for extensive disease 8.9 versus 9.9 months, all in favor of the alternating treatment. Two‐year survival rate for all patients was 6% versus 9%, for limited disease 11% versus 14%, and for extensive disease 3% versus 6%, all preferring the alternating treatment mode. Progression‐free survival demonstrated a strong correlation to the extent of response irrespective of the treatment regimen applied. Toxicity included 11 lethal and 8 life‐threatening complications with a higher frequency in the alternating treatment arm. These results suggest that alternating treatment of SCLC with different drug combinations is more effective than sequential application of CAV. Cancer 59:1072‐1082, 1987.

Atypical mycosis fungoides with cerebral involvement

SummaryThis report concerns a 17-year-old male patient with atypical mycosis fungoides (m.f.). Initial examination revealed generalized lymphoma and uncharacteristic livid skin efflorescence. The patient developed bone marrow involvement and meningeal leukaemia 6 months later. Diagnosis was confirmed by immunohistochemistry and electron microscopy. Aggressive chemotherapy yielded no response.

Carcinoembryonic Antigen, α1-Fetoprotein, Ferritin and α2-Pregnancy Associated Glycoprotein in the Serum of Lung Cancer Patients and its Demonstration in Lung Tumor Tissues

Levels of carcinoembryonic antigen (CEA), alpha-feto-protein (AFP), ferritin and α2-pregnancy associated glycoprotein (Alpha-2-PAG) were determined in patients with confirmed lung cancer at

Acute Allergic Reaction Due to Vincristine Sulfate

A patient suffering from Hodgkin’s disease exhibiting acute allergic reaction to vincristine sulfate with mild to moderate dermatologic and cardiovascular signs is described. The change of therapy to vindesine sulfate led to relief of all symptoms. The therapeutic effectiveness of the altered protocol remained unchanged and no other or amplified side effects appeared.

Zirkulierende Immunkomplexe beim Bronchialkarzinom: Beziehungen zum Ausbreitungsstadium der Erkrankung und zur Therapie

SummaryIn sera of 72 patients with lung cancer, 20 patients with various benign lung diseases and 34 age matched controls circulating immune complexes were determined by column chromatography on Sepharose 6 B and subsequent testing of the eluate for macromolecular IgG as well as by inhibition of radiolabelled C1q binding to sensitized sheep erythrocytes. Whereas in both control and benign lung disease-sera complexes could be detected in less than 5%, sera of lung cancer patients showed macromolecular IgG in 83% and C1q reactive material in 53% at the time of diagnosis. Patients with metastases exhibited a significantly higher percentage of positive reactions than those without metastases (macromolecular IgG 93%/68%, C1q 71%/28%). The size of the complexes increased with the extent of disease. So far, no significant changes in circulating immune complexes could be demonstrated if pretherapeutic values were compared with those after X-ray-, chemo- or immunotherapy with one exception, which is an increase of C1q reactive material after radiotherapy.ZusammenfassungZirkulierende Immunkomplexe wurden im Serum von 72 Patienten mit Bronchialkarzinom, 20 Patienten mit verschiedenen gutartigen Lungenerkrankungen und 34 altersentsprechenden Kontrollen mit Hilfe der Säulenchromatographie (Sepharose 6 B) und dem C1q-Deviationstest (Hemmung der Bindung von radioaktiv markiertem C1q an sensibilisierte Schafserythrozyten) bestimmt. Während bei den Kontrollen und bei den Patienten mit nicht malignen Lungenerkrankungen zirkulierende Immunkomplexe in weniger als 5% nachgewiesen wurden, konnten mit der Säulenchromatographie in 83% und mit dem C1q-Deviationstest in 53% der Seren von Patienten mit Bronchialkarzinom makromolekulares IgG bzw. C1q reaktives Material zum Zeitpunkt der Diagnose bestimmt werden. Patienten mit Metastasen zeigten in einem signifikant höheren Prozentsatz einen positiven Komplexnachweis als Patienten ohne Metastasen (makromolekulares IgG 94%/68%, C1q 71%/28%). Mit fortschreitender Erkrankung stieg das Molekulargewicht der Immunkomplexe an. Der Nachweis zirkulierender Immunkomplexe vor und nach Strahlen-, Chemo- und Immuntherapie ergab keinen signifikanten Unterschied mit Ausnahme eines Anstiegs von C1q reaktivem Material nach Strahlentherapie.In sera of 72 patients with lung cancer, 20 patients with various benign lung diseases and 34 age matched controls circulating immune complexes were determined by column chromatography on Sepharose 6 B and subsequent testing of the eluate for macromolecular IgG as well as by inhibition of radiolabelled C1q binding to sensitized sheep erythrocytes. Whereas in both control and benign lung disease-sera complexes could be detected in less than 5%, sera of lung cancer patients showed macromolecular IgG in 83% and C1q reactive material in 53% at the time of diagnosis. Patients with metastases exhibited a significantly higher percentage of positive reactions than those without metastases (macromolecular IgG 93%/68%, C1q 71%/28%). The size of the complexes increased with the extent of disease. So far, no signficiant changes in circulating immune complexes could be demonstrated id pretherapeutic values were compared with those after X-ray-, chemo- or immunotherapy with one exception, which is an increase of C1q reactive material after radiotherapy.

[Factor XIII deficiency in adults with acute leukemia: results of a substitution therapy with factor XIII (author's transl)].

A decrease in fibrin stabilizing factor (Factor XIII) is the most frequent coagulation disorder seen in adults with acute leukemia. Patients with prominent reduction of factor XIII (FSF) (less than 50%) were substituted with a factor XIII concentrate from human placenta, and factor XIII plasma concentration and bleeding tendency were followed up during the course of the disease. After substitution plasma, factor XIII activity went up to normal levels in most of the patients. As compared to the course of 12 patients with distinct factor XIII reduction without factor XIII therapy, there were less bleeding complications in 13 courses of patients with prominent reduction of factor XIII substituted with factor XIII concentrate and in 11 with normal or only slightly reduced factor XIII levels.SummaryA decrease in fibrin stabilizing factor (factor XIII) is the most frequent coagulation disorder seen in adults with acute leukemia. Patients with prominent reduction of factor XIII (FSF) (<50%) were substituted with a factor XIII concentrate from human placenta, and factor XIII plasma concentration and bleeding tendency were followed up during the course of the disease.After substitution plasma, factor XIII activity went up to normal levels in most of the patients. As compared to the course of 12 patients with distinct factor XIII reduction without factor XIII therapy, there were less bleeding complications in 13 courses of patients with prominent reduction of factor XIII substituted with factor XIII concentrate and in 11 with normal or only slightly reduced factor XIII levels.ZusammenfassungDie häufigste Form der Koagulopathie bei akuter Erwachsenen-Leukämie ist eine Verminderung von Fibrin stabilisierendem Faktor (Faktor XIII). Patienten mit deutlichem Faktor XIII-Mangel (FSF) (<50%) wurden mit einem Faktor XIII-Konzentrat aus menschlicher Plazenta substituiert und die Plasmakonzentration von Faktor XIII im Verlauf bestimmt. Durch die Substitution war fast immer eine schnelle Normalisierung des Faktor XIII-Spiegels zu erzielen. 13 Verläufe von Patienten mit deutlichem Faktor XIII-Mangel mit Substitution und 11 mit normalem oder nur mäßig vermindertem Faktor XIII zeigten weniger Blutungskomplikationen als eine Vergleichsgruppe von 12 Verläufen von Patienten mit deutlichem Faktor XIII-Mangel ohne Substitution.

Ectopically Produced Calcitonin in Human Hemoblastoses

SummaryThe incidence of elevated serum levels of immunoreactive calcitonin (CT) in human myeloproliferative and lymphoproliferative disorders was investigated. On the basis of twice the normal range, about 45% of patients with acute leukemia and blast crisis of chronic myelocytic leukemia (CML) showed elevated serum levels of CT. Markedly elevated levels (> 1,000 pg/ml) were only found in this group. Since immunoreactive CT dropped to normal or only slightly elevated levels in remission and increased again before or during relapse, serum CT levels seem to reflect the activity of the disease. However, in patients with chronic leukemia, Hodgkins and non-Hodgkins lymphoma, a lower incidence and only slightly elevated serum values were found. In addition, the molecular weight of the proteohormone in serum specimen and cell extracts was investigated by gel chromatography. Besides physiological CT, different high-molecular weight forms of the hormone could be demonstrated in serum and in cell extracts. Extracts of leukemic cells revealed higher molecular forms only. It is suggested that the proteohormone is ectopically produced by leukemic cells.ZusammenfassungDas Vorkommen erhöhter Serumspiegel von immunreaktivem Calcitonin (CT) wurde bei menschlichen myeloproliferativen und lymphoproliferativen Erkrankungen untersucht. Unter Zugrundelegung des doppelten oberen Normalbereiches zeigten etwa 45% der Patienten mit akuter Leukämie und mit Blastenschub bei chronischer myeloischer Leukämie erhöhte Calcitonin-Serumspiegel. Extrem erhöhte Werte (> 1000 pg/ml) waren nur in dieser Patientengruppe nachweisbar. Mit dem Eintritt einer Remission kam es zu einem Abfall oder einer Normalisierung der CT-Werte, während bei Eintreten eines Rezidivs ein frühzeitiger Wiederanstieg beobachtet wurde. Dies läßt annehmen, daß die Serumspiegel die Aktivität der Erkrankung wiedergeben. Bei Patienten mit chronischen Leukämien, Morbus Hodgkin und Nicht-Hodgkin-Lymphomen war die Häufigkeit und das Ausmaß der Calcitoninerhöhung im Serum deutlich geringer. Darüber hinaus wurde die Molekulargewichtsverteilung des Proteohormons in Serumproben und Zellextrakten durch Gelchromatographie untersucht. Neben dem physiologischen Hormon fanden sich unterschiedliche hochmolekulare Formen im Serum und in Milzzellextrakten. In Leukämiezellextrakten war ausschließlich hochmolekulares Calcitonin nachweisbar. Es wird angenommen, daß Calcitonin ektop durch die leukämischen Zellen produziert wird.