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Biomedical subjects

S Villa

Publications and source records attributed to S Villa.

At least 127 records · Page 7Linked to original sources
PubMedDate not supplied

Rapid and complete hemopoietic reconstitution following combined transplantation of autologous blood and bone marrow cells. A changing role for high dose chemo-radiotherapy?

The role of high dose chemo-radiotherapy with autologous bone marrow transplantation in the treatment of neoplasia remains to be clearly defined. Because of the iatrogenic morbidity, mortality and high cost of the supportive care required during the post-transplantation period of prolonged marrow aplasia, intensive therapy remains a sophisticated procedure lacking proper evaluation in clinical trials. We report here that when autologous bone marrow cells are supplemented with a small number of peripheral blood nucleated cells collected after prior myelosuppressive chemotherapy, complete hematological recovery is so prompt that myeloid toxicity appears no longer the major limiting factor of high-dose chemo-radiotherapy. The increased therapeutic index made possible by the procedure will allow us to address the issue of whether intensive cytoreductive therapy can be useful as initial treatment of selected tumors with curative intent.

Adolescent↗
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Synthesis and mu-opioid receptor affinity of a new series of nitro substituted 3,8-diazabicyclo[3.2.1]octane derivatives.

A new series of analogues (1c-j; 2c-i) of the previously reported analgesic 3,8-diazabicyclo[3.2.1]octanes (1a,b; 2a,b) was synthesized and tested for their affinity towards mu-opioid receptors. Modifications were introduced either at the cinnamyl or the acyl side chains. The majority of the new compounds, with the exception of 1c,j and 2c, showed Ki values better or comparable with those of the models.

Animals↗
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Benzocondensed derivatives as rigid analogues of the mu-opioid agonist 3(8)-cinnamyl-8(3)-propionyl-3,8-diazabicyclo[3.2.1]octanes: synthesis, modeling, and affinity.

A new series of rigid analogues (1a-g, 2a-g) of the previously reported analgesic 3-cinnamyl-8-propionyl-3,8-diazabicyclo[3.2.1]octane (I) and its reverted isomer 3-propionyl-8-cinnamyl (II) were synthesized, in which the cinnamyl substituent is incorporated in benzocondensed bicyclic systems. Binding assays for the affinity towards mu receptors indicated that, while in the reverted series 2 the beta-naphthylmethyl (2d) and the benzocycloheptenylmethyl derivative (2g) favorably compared with II, all compounds 1 displayed a mu-affinity lower than that of the parent I. Modeling studies suggest that the flexibility of the cinnamyl side chain plays an important role for activity.

Analgesics, Opioid↗
PubMedDate not supplied

Utility fo gallium-67 in determining the radicality of lymph node dissections of the neck for metastatic lymph nodes with extranodal spread in patients affected by carcinoma of the head and neck.

AIMS AND BACKGROUND: Based on the fact that scintigraphy more readily reveals uptake of a radioisotope in a superficial position owing to incomplete surgical radicality, the authors examined by 67Ga scintigraphy a group of patients who had undergone dissection of lymph nodes of the neck from carcinoma with extranodal spread. They then checked the follow-up to ascertain the efficacy of 67Ga scintigraphy in relation to the eventual recurrences in the soft tissues of the neck. METHODS: A group of 136 patients were examined by 67Ga scintigraphy and followed for a minimum of 3 years after complementary radiotherapy. A group of 20 patients with no lymph node metastases was used as control to evaluate eventual false positives or false negatives. RESULTS: Recurrences in the soft tissues of the neck occurred in 35 (42.7%) of the 82 patients positive at 67Ga scintigraphy and in 6 (11.1%) of the 54 patients negative at the examination (P = 0.0001). All the patients in the control group were negative at 67Ga scintigraphy and without recurrences. CONCLUSIONS: 67Ga scintigraphy can give reliable information on the risk of recurrences in the soft tissues of the neck. Since in spite of postoperative radiotherapy the percentage of local recurrences in cases with positive 67Ga scintigraphy was rather high (42.7%), the authors propose a scheme of radiotherapy based on administration of a higher dose per fraction on the scintigraphically positive area.

Adult↗
PubMedDate not supplied

Second-line therapy with interferon-alpha plus vinblastine in metastatic renal cell cancer patients progressed under interleukin-2 subcutaneous immunotherapy.

AIMS AND BACKGROUND: Interferon (IFN) +/- vinblastine (VNB) has appeared to be effective as first-line therapy of metastatic renal cell cancer. This study was performed to establish the efficacy of IFN plus VNB in metastatic RCC previously treated with interleukin-2 (IL-2). METHODS: The study included 14 metastatic renal cell cancer patients who did not respond to IL-2 subcutaneous therapy or who relapsed after initial response or stable disease. IFN-alpha 2a was given subcutaneously at 3 million U thrice a week in association with VNB (0.1 mg/kg i.v. every 21 days) until progression or toxicity. Patients were considered as evaluable when they were treated for at least 1 month. RESULTS: Evaluable patients were 13/14. No patient had a complete response. Partial response was achieved in 2/13 (15%) patients. Stable disease was seen in 5/13 patients, and the last 6 progressed. CONCLUSIONS: This study, by showing a tumor response rate comparable to that reported with first-line therapy, suggests that previous IL-2 immunotherapy does not influence negatively the efficacy of IFN+VNB in metastatic renal cell cancer.

Aged↗
PubMedDate not supplied

Indications, results and techniques of radiotherapy in the treatment of small-cell lung cancer.

AIMS AND BACKGROUND: To define the role of radiotherapy in the treatment of small-cell lung cancer (SCLC) on the basis of clinical data reported in the medical literature. METHODS: Published reports are critically reviewed, with particular attention to randomized trials. RESULTS: Thoracic radiotherapy has an important role in improving local control and 3-year survival in limited-stage SCLC; radiation should be delivered early in the course of the chemotherapy program, avoiding large volumes and total doses exceeding 40-50 Gy. Thoracic radiotherapy probably has no role in resected patients treated with adjuvant chemotherapy and may even be detrimental in patients with extensive SCLC. Prophylactic cranial irradiation has been shown to reduce the risk of brain relapse, but it is not associated with a consistent increase in survival or cure rate: its use in clinical practice is therefore not advised. CONCLUSIONS: Survival rates approaching 50% at 2 years are now possible in limited SCLC with the integrated effort of the surgeon, the medical oncologist and the radiation oncologist; their strict cooperation appears to be of the utmost importance in the earliest phase of treatment planning.

Brain Neoplasms↗
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Altered fractionation radiotherapy in lung cancer.

Clinical trials on altered fractionation radiotherapy (RT) regimens currently play a significant role in lung cancer, due to the importance of local control and to the disappointing therapeutic results in this disease. In non-small-cell lung cancer (NSCLC) two strategies are being actively investigated: hyperfractionation with a "curative" aim, and hypofractionation with a palliative aim; in small-cell lung cancer (SCLC) altered fractionation seems to play a minor role at this moment. In this review paper the results of reported randomised trials are summarised and discussed. Conclusions may indicate that through hyperfractionation, particularly if accelerated, clinical outcome of non-metastatic NSCLC patients can be improved; data are however not sufficiently mature to advise its use outside controlled clinical trials. In the palliative setting, hypofractionation should be considered standard treatment.

Carcinoma, Non-Small-Cell Lung↗
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The role of radiotherapy in the treatment of carcinoma of the prostate: a survey of clinical practices in Lombardy, Italy, by the AIRO-Lombardia Cooperative Group. Italian Association for Radiation Oncology.

AIMS AND BACKGROUND: We report the results of a survey performed in 1994 by the AIRO-Lombardia Cooperative Group, on the clinical patterns of radiation treatment for prostatic carcinoma in Lombardy, Italy, involving all radiotherapy centers serving an overall local population of about 8,800,000 people. METHODS: A questionnaire was sent to all 13 radiotherapy centers throughout Lombardy, asking for demographic and treatment details concerning the local population of patients with a localized (T1-4, N0-1, M0) carcinoma of the prostate treated with radiotherapy; 12 centers responded, making the basis for the present report. RESULTS: Analysis of collected data showed that in Lombardy: a) approximately 400 patients per year are irradiated for a localized carcinoma of the prostate, accounting for less than 30% of the total expected number of patients with this disease presentation; b) a complete staging (with PSA, transrectal ultrasonography, abdomino-pelvic CT or MRI scan and total-body bone scan) is performed in over 95% of patients before initiating radiotherapy; c) significant differences exist between radiotherapy centers as regards treatment planning and delivery. CONCLUSIONS: An urgent need exists for implementing procedures aimed at standardizing radiotherapy procedures within Lombardy.

Carcinoma↗
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Minimal requirements in prostate cancer irradiation: a consensus document by the AIRO Lombardia Cooperative Group.

PURPOSE: With the aim of establishing clinical and technical criteria to homogenize radiotherapy practice, a working group of AIRO-Lombardia (Associazione Italiana di Radioterapia Oncologica--Gruppo regionale della Lombardia) has tried to define minimal requirements for radical and postoperative irradiation in prostate cancer. The document has been structured in such a way as to be also of interest to the urological and medical oncology communities. METHODS: The working group, composed of representatives of most of the regional radiotherapy departments in the Lombardy region, had monthly meetings during 1996 and 1997. The document on minimal requirements has been derived from the participants' combined experience and knowledge, from review of the literature, and from a 1995 regional survey on current practice of prostate irradiation. RESULTS: Minimal requirements for radical and postoperative irradiation of prostate cancer have been defined with respect to treatment strategies, pre-treatment diagnostic evaluation and staging, treatment prescription, preparation and execution, and quality assurance procedures. CONCLUSION: Standards of reference for minimal requirements in prostate cancer irradiation adapted to the regional structures and resources have been defined.

Humans↗
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A clinical study of taxotere versus taxotere plus the antiprolactinemic agent bromocriptine in metastatic breast cancer pretreated with anthracyclines.

Prolactin (PRL) constitutes a growth factor for breast cancer cell proliferation and abnormally elevated blood concentrations of PRL are associated with poor prognosis and reduced efficacy of antitumor therapies in metastatic breast carcinoma. It has already been demonstrated that low-dose bromocriptine, an antiprolactinemic long-acting dopaminergic drug, normalizes PRL blood concentrations in metastatic breast cancer patients with abnormally elevated PRL levels. In addition, previous clinical studies have already demonstrated a lower efficacy of chemotherapy with taxotere in metastatic breast cancer, with persistent hyperprolactinemia. We planned a controlled clinical study to evaluate the influence of a concomitant administration of the antiprolactinemic drug bromocriptine on the efficacy of chemotherapy with taxotere, in metastatic breast cancer patients progressing after chemotherapeutic combinations containing anthracyclines. The study included 30 randomized consecutive patients treated with taxotere alone or taxotere plus bromocriptine. Taxotere was given I.V. at 100 mg/m2 every 21 days for 3 cycles. Bromocriptine was given orally at 2.5 mg/day every day until the end of the chemotherapeutic treatment. Bromocriptine therapy induced a significant decline in PRL mean blood concentrations compared to patients treated by chemotherapy alone. No complete response was obtained. A partial response (PR) occurred in 5 out of 14 (36%) patients treated with taxotere plus bromocriptine and in only 2 out of 16 (13%) patients treated with taxotere alone. Moreover, a stable disease (SD) was obtained in 5 out of 16 patients treated with taxotere alone and in 7 out of 14 patients concomitantly treated with bromocriptine. Therefore, the percent of non-progressive disease (PR + SD) achieved in patients treated with taxotere plus bromocriptine was significantly higher with respect to that found in patients treated with taxotere alone (12 out of 14 vs 7 out of 16, p < 0.025). This preliminary clinical study would suggest that the inhibition of PRL secretion by antiprolactinemic drugs such as bromocriptine may enhance the efficacy of chemotherapy for metastatic breast cancer.

Aged↗
PubMedDate not supplied

Antiprolactinemic approach in the treatment of metastatic breast cancer: a phase II study of polyneuroendocrine therapy with LHRH-analogue, tamoxifen and the long-acting antiprolactinemic drug cabergoline.

Despite the well-demonstrated stimulatory role of prolactin (PRL) on breast cancer cell growth and the possible existence of a PRL-dependency in estrogen-independent mammary tumors, the therapeutic role of the antiprolactinemic drugs in the treatment of human breast cancer has still to be investigated and defined. Previous preliminary studies have already shown that the concomitant administration of antiprolactinemic agents may enhance the efficacy of cancer chemotherapy for breast carcinoma, whereas their impact on the efficacy of the endocrine therapy is still unknown. At present, the classic endocrine therapy for breast cancer consists of anti-estrogens plus LHRH-analogue. The concomitant administration of antiprolactinemic drugs could enhance the efficacy of treatment by blocking not only the action of estrogens, but also that of another growth factor for breast cancer, such as PRL. The present phase II study was performed to evaluate the efficacy and tolerability of a polyneuroendocrine approach for breast cancer, consisting of LHRH-analogue plus the anti-estrogen tamoxifen plus a long-acting antiprolactinemic agent, cabergoline. The study included 14 consecutive metastatic breast cancer women, heavily pretreated with the standard anticancer therapies and for whom no other conventional treatment was available. The LHRH-analogue, triptorelin, was given intramuscularly at a dose of 3.75 mg every 28 days, tamoxifen was given orally at 20 mg/day and cabergoline was given orally at 0.5 mg once/week. The clinical response consisted of partial response (PR) in 4 out of 14 (29%) patients, including one who had progressed on a previous treatment with triptorelin plus tamoxifen alone. A stable disease (SD) was achieved in another 5 patients, whereas the other 5 patients had a progressive disease (PD). Mean serum levels of PRL significantly decreased on treatment within the first month of therapy, and its decline was significantly more evident in patients with PR or SD than in those with PD. The treatment was well-tolerated in all patients, and in particular no cabergoline-related toxicity occurred. This preliminary study would suggest that the association of the long-acting antiprolactinemic drug cabergoline may further enhance the efficacy of the classical endocrine therapy for advanced breast cancer with anti-estrogens plus LHRH-analogues.

Adult↗
PubMedDate not supplied

Biomodulation of cancer chemotherapy for metastatic colorectal cancer: a randomized study of weekly low-dose irinotecan alone versus irinotecan plus the oncostatic pineal hormone melatonin in metastatic colorectal cancer patients progressing on 5-fluorouracil-containing combinations.

Recent advances in immunobiological knowledge have suggested the possibility of enhancing the therapeutic activity of various chemotherapeutic agents by a concomitant administration of anti-oxidant drugs and/or immunomodulating neurohormones. In particular, the pineal neurohormone melatonin (MLT), which is able to exert both antioxidant and immunomodulating effects, has been proven to enhance the efficacy of various chemotherapeutic drugs, namely cisplatin, anthracyclines and 5-fluorouracil, whereas at present there are no data about its possible influence on cytotoxic drugs effective in the treatment of colon cancer other than 5-fluorouracil, such as irinotecan (CPT-11). The present study was performed to evaluate the influence of a concomitant administration of MLT on CPT-11 therapeutic activity in metastatic colorectal cancer. The study included 30 metastatic colorectal cancer patients progressing after at least one previous chemotherapeutic line containing 5-fluorouracil, who were randomized to be treated with CPT-11 alone or CPT-11 plus MLT. According to a weekly low-dose schedule, CPT-11 was given i.v. at 125 mg/m2/week for 9 consecutive weeks. MLT was administered orally at 20 mg/day during the dark period of the day. No complete response was observed. A partial response (PR) was achieved in 2 out of 16 patients treated with CPT-11 alone and in 5 out of 14 patients concomitantly treated with MLT. Moreover, a stable disease (SD) was obtained in 5 out of 16 patients treated with CPT-11 alone and in 7 out of 14 patients treated with CPT-11 plus MLT. Therefore, the percent of disease-control achieved in patients concomitantly treated with MLT was significantly higher than that observed in those treated with chemotherapy alone (12 out of 14 vs 7 out of 16, p < 0.05). The only important toxicity was diarrhoea grade 3-4, which occurred in 6 out of 16 patients treated with CPT-11 alone and in 4 out of 14 patients treated with CPT-11 plus MLT, which required a 50% dose reduction. However, taken together, patients treated with CPT-11 at 50% of the planned dose showed a percent of disease control comparable to that achieved in patients who had no dose reduction (6 out of 10 vs 13 out of 20). This preliminary study shows that the efficacy of weekly low-dose CPT-11 in pretreated metastatic colorectal cancer patients may be enhanced by a concomitant daily administration of the pineal hormone MLT, according to the results previously reported for other chemotherapeutic agents. Moreover, since the dose reduction of CPT-11 does not influence its efficacy, the dose of CPT-11 for successive studies might be not greater than 70 mg/m2.

Adjuvants, Immunologic↗
PubMedDate not supplied

A psychoncological study of lymphocyte subpopulations in relation to pleasure-related neurobiochemistry and sexual and spiritual profile to Rorschach's test in early or advanced cancer patients.

According to recent advances in psychoneuroimmunology concerning the neurobiochemistry of emotions, the pshychological status of cancer patients should be investigated in relation to the function of the psychoneurodocrine system, in an attempt to put into evidence possible cancer progression-related alterations, particularly those involving the dopaminergic pathways, which play a fundamental role in the perception of pleasure. In fact, the decreased capacity of feeling pleasure is one of the most frequent psychic symptoms occurring in cancer patients. Rorschach's test has been proven to be an appropriate psychological tool to investigate psychic condition including sexual and spiritual profiles. On this basis, a study was planned to evaluate if a relation exists between psychological response to Rorschach's test and immunoneuroendocrine status of cancer patients. The immune status was investigated by measuring lymphocyte subsets and serum levels of IL-2 and IL-10. The neuroendocrine status was analyzed by evaluating the endocrine response of PRL, GH and cortisol to an oral administration of apomorphine (0.01 mg/kg b.w.), a dopaminergic agent able to explore dopaminergic sensitivity. The study included 40 cancer patients (breast cancer: 15; colorectal cancer: 14; lung cancer: 11), 21 of whom showed distant organ metastases. Rorschach's test demonstrated a simultaneous suppression of sexual and spiritual profiles in 31/40 (78%) patients, without significant differences in relation to either tumor histotype or disease state. A normal decline in PRL levels and a normal increase in those of GH and cortisol was observed in 29/40 (73%), 5/40 (13%) and 9/40 (23%) patients. The percent of normal responses of PRL, GH and cortisol was higher in patients with normal than in those with altered response to Rorschach's test, even though only the difference in PRL and cortisol response was statistically significant. Patients with normal sexual and spiritual expression at Rorschach's test showed a significantly higher number of total lymphocytes, T lymphocytes, T helper lymphocytes and NK cells with respect to the patients with altered psychological response, whereas no difference was found in T cytotoxic lymphocyte mean number. IL-2 and IL-10 mean serum concentrations were lower and higher, respectively, in patients with altered than in those with normal response to Rorschach's test, even though only the difference in IL-10 values was statitistically significant. This preliminary study, carried out to analyze the psychological status of cancer patients in relation to neuroendocrine and immune conditions, would suggest that neoplastic disease is characterized by a simultaneous suppression of sexual and spiritual profiles, and that this is associated with neuroendocrine alterations and immunosuppression.

Administration, Oral↗
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Detection of occult leukemic cells in the autologous bone marrow graft of a patient with T-cell acute lymphoblastic leukemia by a highly specific and sensitive assay.

A patient with T-cell acute lymphoblastic leukemia (T-ALL) in second remission was treated with high doses of chemotherapy and radiotherapy, followed by transplantation of autologous bone marrow purged ex-vivo with an anti-CD5-saporin immunotoxin (OKT1-SAP). Prior to transplantation the bone marrow graft had been considered in complete remission, as assessed by morphology and immunophenotyping. Twenty-two days after transplantation, the disease relapsed in the bone marrow with the same phenotype as at the onset. Retrospective analysis of the transplanted marrow cells by a recently developed high sensitivity and specificity assay (HSS assay), involving immunologic fractionation and T-cell receptor rearrangement analysis, revealed a graft contamination of approximately 0.5% malignant T-cells. This finding, together with the early post-transplant leukemic relapse, strongly suggests that the bone marrow was the source of the leukemic cells. The data are discussed for their implications on residual leukemia detection by gene rearrangement studies.

Adolescent↗