Retrovirus particles with type C morphology were found in two T-cell lymphoblastoid cell lines, HUT 102 and CTCL-3, and in fresh peripheral blood lymphocytes obtained from a patient with a cutaneous T-cell lymphoma (mycosis fungoides). The cell lines continuously produce these viruses, which are collectively referred to as HTLV, strain CR(HTLVCR). Originally, the production of virus from HUT 102 cells required induction with 5-iodo-2′-deoxyuridine, but the cell line became a constitutive producer of virus at its 56th passage. Cell line CTCL-3 has been a constitutive producer of virus from its second passage in culture. Both mature and immature extracellular virus particles were seen in thin-section electron micrographs of fixed, pelleted cellular material; on occasion, typical type C budding virus particles were seen. No form of intracellular virus particle has been seen. Mature particles were 100-110 nm in diameter, consisted of an electron-dense core surrounded by an outer membrane separated by an electron-lucent region, banded at a density of 1.16 g/ml on a continuous 25-65% sucrose gradient, and contained 70S RNA and a DNA polymerase activity typical of viral reverse transcriptase (RT; RNA-dependent DNA nucleotidyltransferase). Under certain conditions of assay, HTLVCR RT showed cation preference for Mg2+ over Mn2+, distinct from the characteristics of cellular DNA polymerases purified from human lymphocytes and the RT from most type C viruses. Antibodies to cellular DNA polymerase γ and anti-bodies against RT purified from several animal retroviruses failed to detectably interact with HTLVCR RT under conditions that were positive for the respective homologous DNA polymerase, demonstrating a lack of close relationship of HTLVCR RT to cellular DNA polymerases γ or RT of these viruses. Six major proteins, with sizes of approximately 10,000, 13,000, 19,000, 24,000, 42,000, and 52,000 daltons, were apparent when doubly banded, disrupted HTLVCR particles were chromatographed on a NaDodSO4/polyacrylamide gel. The number of these particle-associated proteins is consistent with the expected proteins of a retrovirus, but the sizes of some are distinct from those of most known retroviruses of the primate subgroups.

https://www.pnas.org/content/pnas/77/12/7415.full.pdf

Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma

Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

https://www.unitypoint.org/desmoines/filesimages/Cancer%20Education/Oncology%20Nursing%20Conference/2015/2014%20NCCN%20Clin%20Pract%20Guidelines%20Male%20Sex%20Dysf.pdf

Clinical practice guidelines in oncology

A new international staging system for lung cancer

Δ9-Tetrahydrocannabinol (THC) is the main source of the pharmacological effects caused by the consumption of cannabis, both the marijuana-like action and the medicinal benefits of the plant. However, its acid metabolite THC-COOH, the non-psychotropic cannabidiol (CBD), several cannabinoid analogues and newly discovered modulators of the endogenous cannabinoid system are also promising candidates for clinical research and therapeutic uses. Cannabinoids exert many effects through activation of G-protein-coupled cannabinoid receptors in the brain and peripheral tissues. Additionally, there is evidence for nonreceptor-dependent mechanisms. Natural cannabis products and single cannabinoids are usually inhaled or taken orally; the rectal route, sublingual administration, transdermal delivery, eye drops and aerosols have only been used in a few studies and are of little relevance in practice today. The pharmacokinetics of THC vary as a function of its route of administration. Pulmonary assimilation of inhaled THC causes a maximum plasma concentration within minutes, psychotropic effects start within seconds to a few minutes, reach a maximum after 15–30 minutes, and taper off within 2–3 hours. Following oral ingestion, psychotropic effects set in with a delay of 30–90 minutes, reach their maximum after 2–3 hours and last for about 4–12 hours, depending on dose and specific effect. At doses exceeding the psychotropic threshold, ingestion of cannabis usually causes enhanced well-being and relaxation with an intensification of ordinary sensory experiences. The most important acute adverse effects caused by overdosing are anxiety and panic attacks, and with regard to somatic effects increased heart rate and changes in blood pressure. Regular use of cannabis may lead to dependency and to a mild withdrawal syndrome. The existence and the intensity of possible long-term adverse effects on psyche and cognition, immune system, fertility and pregnancy remain controversial. They are reported to be low in humans and do not preclude legitimate therapeutic use of cannabis-based drugs. Properties of cannabis that might be of therapeutic use include analgesia, muscle relaxation, immunosuppression, sedation, improvement of mood, stimulation of appetite, antiemesis, lowering of intraocular pressure, bronchodilation, neuroprotection and induction of apoptosis in cancer cells.

Pharmacokinetics and Pharmacodynamics of Cannabinoids

Small Cell Lung Cancer

Thirty-two patients (27, extensive disease; five, regional disease) with histologically documented small cell carcinoma entered a randomized study to determine the efficacy of intensive induction chemotherapy. The necessity of a protected environment (laminar air flow room) during this treatment was also evaluated. Patients received high-dose or standard-dose cyclophosphamide, methotrexate, and CCNU (CMC) during the first 6 weeks of treatment. Subsequent maintenance therapy consisted of standard-dose CMC until disease progression. In 23 patients treated with high-dose chemotherapy there were responses in 96% (30% complete). Standard-dose chemotherapy gave responses in 45%, none of which were complete. Median survival correlated with completeness of response and was 16+ months for the seven complete responders. Patients receiving high-dose CMC spent an average of 10 days with neutrophil counts less than 1000/mm3. There was only one documented, non-fatal infection. High-dose chemotherapy gives better responses and longer survival than previously utilized standard doses of the same drugs. Patients could safely be treated in the hospital ward.

Intensive chemotherapy of small cell bronchogenic carcinoma.

Biopsy specimens from 19 previously untreated lung cancer patients were prospectively diagnosed as small cell carcinoma with a large cell component. The patients were thoroughly staged and received intensive combination chemotherapy. They represented 12% of all small cell carcinoma cases eligible for aggressive chemotherapy protocols during a 5.5 year period. To determine whether the clinical behavior of this “mixed” histologic variant differed from the other histologic subtypes of small cell lung cancer, we compared these 19 patients to a concurrent group of 103 patients with only small cell cancer in their diagnostic biopsies given equivalent therapy. The “mixed” histology patients were comparable to the “pure” small cell group in age, performance status, extent of disease, and frequency of bone marrow, liver, bone, and central nervous system metastases. Their complete plus partial response rate (58%) was significantly less than the response rate for the “pure” small cell patients (91%), their complete response rate was also lower (16 versus 46%), and their overall survival was significantly shorter (median, 6 versus 10.5 months). Mixed histology small cell/large cell carcinoma represents a distinct pathologic variant of small cell carcinoma of the lung, associated with lower response rates and shorter survival than the “pure” small cell subtypes. Since combination chemotherapy yields some complete responses and long-term disease-free survival in these patients, however, aggressive treatment with potentially curative intent should be considered in their management. Cancer 50:2894-2902, 1982.

The clinical behavior of „mixed”︁ small cell/large cell bronchogenic carcinoma compared to „pure”︁ small cell subtypes

Sixty-one protocol-eligible patients with small cell bronchogenic carcinoma received cyclic alternating combination chemotherapy with two or three non-cross-resistant drug combinations. No chest or prophylactic brain radiation therapy was used. Twenty-eight months after starting treatment, disease-free survival was 23% for patients achieving a complete response (CR) and 13% overall. Initial treatment consisted of high-dose cyclophosphamide, methotrexate, and CCNU (CMC) for 6 weeks. Patients then received vincristine, adriamycin, and procarbazine (VAP) for 6 weeks. The addition of VAP increased the CR rate from 42% to 74% in limited-disease patients and from 24% to 36% in extensive-disease patients. Half of the patients were randomized to a third combination of VO-16-213 and ifosfamide. These patients were cycled at 6-week intervals through the three drug regimens while the remaining patients were cycled between CMC and VAP. The addition of VP-16-213 and ifosfamide did not increase the CR rate or prolong survival. Only complete responders survived beyond 24 months. Sequential use of non-cross-resistant drug combinations represents one method for increasing the CR rate.

Cyclic alternating combination chemotherapy for small cell bronchogenic carcinoma.

The prognostic implications of cigarette smoking were investigated in 112 patients with small cell lung cancer. Twenty had stopped smoking permanently before diagnosis (NS-Prior), 35 had stopped at diagnosis (NS-Dx), and 57 patients continued smoking (S). Therapies included chemotherapy alone or with radiation therapy, with or without thymosin fraction V. The survival difference among the three groups was statistically significant. The NS-Prior patients had the best survival, followed by NS-Dx patients and finally S patients. No S patient has survived, disease free, more than 96 weeks, while three NS-Prior and three NS-Dx patients are disease free 103 to 220 weeks after start of treatment. Thymosin, 60 mg/sq m, yielded survival benefits for the S group only. Continuation of smoking during the treatment of small cell lung cancer was associated with a poor prognosis, while discontinuation of smoking, even at diagnosis, may have beneficial effects on survival. ( JAMA 244:2175-2179, 1980)

Byron E. Fossieck

Papers

Intensive chemotherapy of small cell bronchogenic carcinoma.

The clinical behavior of „mixed”︁ small cell/large cell bronchogenic carcinoma compared to „pure”︁ small cell subtypes

Cyclic alternating combination chemotherapy for small cell bronchogenic carcinoma.

Smoking abstinence and small cell lung cancer survival. An association

Advances in small cell bronchogenic carcinoma.