Effects of systemic acidification of mice with Sarcoma 180.

The effects of dietary-induced acidosis on the growth and rates of complete regression of Sarcoma 180 in mice have been studied. The experiments here reported have demonstrated that mineral acidification of laboratory food produces a late decrease in tumor growth and significantly increases the rates of complete tumor regression. Blood acid-base studies also demonstrate the effects of these diets in altering the acid-base balance, and seemingly, this is independent of starvation and/or ketosis. The relationships of such in vivo acid-base metabolic changes to the control of tumor metabolism are briefly discussed. A therapeutic potential for this preliminary approach is considered.

Undifferentiated epithelial-rich invasive malignant thymoma: complete response to cisplatin, vinblastine, and bleomycin therapy.

Two cases of complete remission plus one almost complete and another partial response of undifferentiated, invasive epithelial malignant thymoma using the combination of cisplatin, vinblastine, and bleomycin (PVB), are reported in four patients treated with this combination. Radiotherapy was instituted after completing the fourth course of chemotherapy in three patients. One patient died from intercurrent infection after the fourth cycle of combination chemotherapy. Three patients remain free of disease at the end of the treatment program. PVB appears to be highly active in this disease and deserves more extensive evaluation in multicenter clinical trials.

Mitogenic inhibition and effect on survival of mice bearing L1210 leukemia using a combination of dehydroascorbic acid and hydroxycobalamin.

The present study was designed to test the effect of a combination of dehydroascorbic acid (DHA) and hydroxycobalamin (vitamin B12) on the survival of mice bearing L1210 leukemia. Results showed a significant increase in survival of treated mice compared with controls (p less than or equal to 0.0001) (Student's t-test). This positive effect was significantly lost when DHA was substituted by ascorbic acid (AA) in the same experimental conditions. In vitro findings also revealed that the DHA-B12 combination specifically inhibited mitoses of L1210 cells while non-neoplastic L929 cells were not affected.

Intra-arterial and intravenous chemotherapy for the treatment of malignant glioma. Preliminary results.

Twenty-one patients with malignant glioma were treated with cis-diamminedichloroplatinum II (CDDP II) 60-90 mg/m2 intra-arterial (I.A.) bolus on day 1 and Carmustine (BCNU) 100 mg/m2 intravenously (I.V.) on days 1 and 2. Three patients received additional Aziridinylbenzoquinone (AZQ) 7 mg/m2 (I.V.) on days 1 and 2. At the time of this treatment, seven patients had local recurrence after previous surgery and radiotherapy. Nine patients had subtotal tumor resection or biopsy, one patient had macroscopic tumor resection, and four patients had no previous surgery because of medical contraindication. Six patients received five or more courses of I.A. and I.V. chemotherapy. Five of these patients showed complete remission (CR) and one had a partial remission (PR) by brain computerized tomography (CT scan). Another 15 patients treated with two to four courses of I.A., and I.V. chemotherapy showed eight partial responses (PR), and seven showed no changes (NC) by brain CT scan. Five patients died with disease. Patients who achieved CR also received radical radiotherapy for remission consolidation. Sixteen patients are still alive; five patients are off treatment, four of these with no evidence of disease (NED), one alive with disease (AWD); and the remaining 11 patients are still on treatment. Toxicity, symptomatic neurological recovery, disease stabilization, and causes of death will be discussed.

Integrating fields of cancer research through pivotal mechanisms and synthetic final pathways: a unifying and creative overview.

From cancer etiopathogenesis to selective apoptosis, from multiple drug resistance to oncogen activation and from the phenomena of spontaneous regression of cancer to certain aspects of cancer chemotherapy, all these subfields of biology and oncology research share some deep-seated, both basic and clinical, essential features and characteristics. Certain apoptosis-inducing agents of unrelated families, ranging from ether lipids to Na(+)/H(+)-antiporter inhibitors to Delta(9)-tetrahydrocannabinol all have been reported to induce selective cancer-cell death. Behind a wide array of intermediary factors and mechanisms involved in their activity, they seem to share common pivotal and/or final pathways in inducing cell death mediated by a 'pathological' accumulation of intracellular hydrogen ions as a mechanism underlying core changes in intracellular signaling pathways. An H(+)-concentration initial perspective indicates that from pathogenesis to apoptosis and multiple drug resistance, as well as oncogen activity, tumor progression and even the phenomenon of spontaneous regression, all can be interpreted from their deep (H(+))-related basic and clinical essential characteristics. This speculative review discusses the potential integration of these previously disparate subfields of cancer research, through a model which also seems to lead toward improving understanding of the fundamental nature of malignant processes. It is concluded that this synthetic and universal approach allows advancement toward a combining of different areas of oncology into deeper and more comprehensive forms of rational understanding, with the hope of paving the way towards more selective, effective and all-encompassing forms of treatment.

The Na+/H+ antiporter in oncology in the light of the spontaneous regression of cancer and cell metabolism.

Multiple metabolic and biochemical interrelationships, as well as the most recent views on mechanisms of malignant cell growth, proliferation, and oncogen activity mediated by the Na+/H+ antiporter, can be integrated from the unitarian point of view of the dynamics of the hydrogen ion to parallel pH-related mechanisms involved in the Spontaneous Regression (SR) of some malignant tumors. Also, pH-related growth inhibitors of the amiloride series are considered as possible agents to be used in the adjuvant and co-adjuvant treatment of some human tumors as well as in the control of the metastatic process and in overcoming cancer multidrug resistance (MDR).

Hierarchical organization, integrations in biology and cancer, balance loss, and a question on modernism.

The hierarchical organization of biological processes is considered in the light of universal interrelationships of each and every factor affecting open systems such as human life. The maintenance of health and/or the production of disease are viewed at different levels of biological organization as related to the dualistic concept. The relative effects of environmental versus genetic tendencies in the pathogenesis of "disease" are mathematically formulated as related to time and location. Psychological determinants are considered as cause and as consequence of the onset of somatic disease. The multifactorial aspects of chronic pathology are seen in relation to dominant tendencies in life and in medical sciences, as well as to individual factors. The "non-specificity" of some aspects of cancer as related to "Adaptation" is advanced. Doubts are raised regarding the ultimate value of modern technological achievements and overspecialization per se, as well as on the lines followed by modern trends in the organization of cancer research. Finally, the increasing need for progressive thoughtful integration versus increasing specialization is stressed.

[Homeostasis, diabetes and cancer]. / Homeostasis, diabetes y cáncer.

There is a large body of evidence to consider that the functional aspects of the metabolism of the cancer cell and hypoinsulinemic diabetes mellitus dwell at both ends of a biochemico-metabolic spectrum representing two opposite homeostatic and pathological tendencies. Furthermore, an initial homeostatic approach based up the acid-base balance and/or its hydrogen ion dynamics, systematically considered at multiple dimensions of knowledge and in different areas and fields of biomedical research, allows to reach a systematic vision and an all-comprehensive and hierarchically organized perspective for the integrated study of both malignant and non-malignant, as well as diabetic, metabolism, while at the same time opens new avenues reaching out towards a better understanding of both the etiopathogenesis of certain epithelial tumors and the chronic complications of diabetes mellitus. Besides, such a unitarian outlook may very well open new ways towards a more comprehensive understanding of the interrelationships among both degenerative processes, and from the bioenergetic to the clinical levels, hopefully leading to better preventive and treatment strategies.

[Combined strategy of cancerous cells: fat and protein metabolism. Conclusions (3rd of 3 parts)]. / Estrategia unitiva de las células cancerosas: metabolismo graso y proteínico. Conclusiones (tercera de tres partes).

The metabolic and biochemical program of neoplastic cells regarding carbohydrate metabolism can be extend to the rest of the metabolism. This gives a rational idea of the global strategy and thermodynamic advantages of malignant cells and of tumors in general as related to the host. A comprehensive, metaenzymatic and transbiochemical approach allows to understand some of the reasons for the limitations found along the last decades by the different chemotherapeutic attempts directed against particular enzymes overexpressed in tumor cells. This indicates that a new vision of the whole problem is preceptive. The overwhelming effects of the hydrogen ion at multiple levels indicates that an initial approach based upon this unifying principle and universal regulatory parameter may provide the initial codes, hints and hunches, of a new synthetic and unitive biological, biomedical and biophysical scientific paradigm. Initially, it already offers the possibility of a new multidisciplinary approach to the prevention and treatment of tumors such as cervical intraepitelial neoplasia.

[Unitary strategy of cancerous cells: hydrocarbon metabolism (1)]. / Estrategia unitiva de las células cancerosas: metabolismo hidrocarbonado (primera de tres partes).

A systematic outlook of metabolism regarding the strategy followed by cancer cells is necessary in order to understand the thermodynamic advantages of these cells and the difficulty found in the treatment of certain malignant diseases. These features show that the present-day vision, the biochemical-analytical-fragmentary-reductionistic approach, is not and it is not likely that it will never be sufficient. Thus, a new paradigm of a different dimension but a the same time complementary to the previous and actual one seems necessary. Therefore, a higher and more comprehensive and outreaching vision, transbiochemical and metaenzymatic, one ecologically and macro and microenvironmentally oriented and finally synthetic and unitive one, appears mandatory. The dynamics of the hydrogen ion as applied to biological processes seems to be able to offer the opportunity to arrive to such kind of unifyng comprehension through and integrated perceptive model at multiple levels of biological, biomedical and biophysical understanding.

[The unitary strategy of cancer cells: the hydrogen ion as a multidimensional unitary factor and carbohydrate metabolism (2)]. / Estrategia unitiva de las células cancerosas: ión de hidrógeno como factor unitario multidimensional y metabolismo hidrocarbonado (segunda de tres partes).

A systematic outlook of metabolism regarding the strategy followed by cancer cells is necessary in order to understand the thermodynamic advantages of these cells and the difficulty found in the treatment of certain malignant diseases. These features show that the present-day vision, the biochemical-analytical-fragmentary-reduccionistic approach, is not and it is not likely that it wil never be sufficient. Thus, a new paradigm of a different dimension but a the same time complementary to the previous and actual one seems necessary. Therefore, a higher and more comprehensive and outreaching vision, transbiochemical and metaenzymatic, one ecologically and macro and microenvironmentally oriented and finally synthetic and unitary one, appears mandatory. The dynamics of the hydrogen ion as applied to biological processes seems to be able to offer the opportunity to arrive to such kind of unifying comprehension through an integrated perceptive model at multiple levels of biological, biomedical and biophysical understanding.

[Lung cancer as a scar tumor: apropos a case and the possible etiopathogenetic mechanisms]. / Cáncer de pulmón como tumor de cicatriz: a propósito de un caso y posibles mecanismos etiopatogénicos.

The true existence of "scar tumors" is still being argued. A case of a 30 years old patient with an adenocarcinoma of the lung which grew on a scar secondary to a motorbike accident that happened 15 years earlier is here presented. The age of the patient, the pathology of the tumor, the radiological demonstration of the tumor progressively growing on and around a preexistent scar, as well as the long period of time that elapsed in between the initial etiological factor and the final diagnosis leave very few doubts about the "scar" origin of this neoplasia. Previously undescribed and possible etiopathogenetic mechanisms of these tumors are considered from the biochemical and energetic points of view.

[Original physiopathological integration and new treatment possibilities and approaches in breast cancer]. / Inéditas integraciones fisiopatológicas y nuevas posibilidades y aproximaciones terapéuticas al cáncer de mama.

The aim of this paper is unify the physiopathological mechanisms of breast cancer proliferation and its hormonal relations. A further objective is to determine a comprehensive integration of the different hormonal therapies, considering new alternatives which are at present in developing stages. We conclude, defining and recommending further ways to focus upon and treat this disease.

Hydrogen ion dynamics and cancer: an appraisal.

The concentration of hydrogen ions plays a critical role in all biochemical processes, including multiple enzymatic reactions, and in the regulation of metabolism. The acid-base aspects of metabolism as applied to cancer are considered. Preliminary data are presented. The primary concept of hydrogen ion dynamics is related to prevention, development, and etiology of carcinogenicity, as well as to the regression of certain malignant malignant tumors. The present overview summarizes, in terms of H+ dynamics, many related concepts in oncologic research and associates and integrates a variety of basic and clinical observations toward better understanding of cancer cell behavior, biology, and host-tumor relationships.

Integrated etiopathogenesis of cancer of mucosal surfaces with emphasis on the digestive tract: an appraisal.

The concept of hydrogen ion concentration [H+] may become the cornerstone of an integrated understanding of the mechanisms leading to cancer of the mucous membranes, mainly of the digestive tract. From basic research to the different situations preceding mucosal malignancies, there is considerable evidence to propose that chronic and deep-seated abnormalities in local pH may have both a direct and an indirect role in the etiology of epithelial human cancer. A high microenvironmental pH also appears to act as a universal mediator and activating factor of many different chemical and biological carcinogens.

Hydrogen ion dynamics and the Na+/H+ exchanger in cancer angiogenesis and antiangiogenesis.

Tumour angiogenesis and cellular pH regulation, mainly represented by Na(+)/H(+) antiporter exchange, have been heretofore considered unrelated subfields of cancer research. In this short review, the available experimental evidence relating these areas of modern cancer research is introduced. This perspective also helps to design a new approach that facilitates the opening and development of novel research lines oriented towards a rational incorporation of anticancer drugs into more selective and less toxic therapeutic protocols. The final aim of these efforts is to control cancer progression and dissemination through the control of tumour angiogenesis. Finally, different antiangiogenic drugs that can already be clinically used to this effect are briefly presented.

Hypercalcemia complicating childhood malignancies: a report of seven cases with some pathophysiological considerations.

A group of seven children with different malignant processes presenting with hypercalcemia was studied. Bone destruction, diffuse metabolic abnormalities, abnormal acid-base homeostasis and recurrent hypercalcemia characterized these patients. A different mechanism leading to the production of hypercalcemia and/or bone destruction by cancer cells is considered. The results of this report suggest that parathyroid hormone production (P.T.H.) by the parathyroid glands is normal and that ectopic secretion of PTH or PTH-like material is negligible in these cases.

Platinum-based combination chemotherapy in non-small cell lung carcinoma.

A series of 35 patients with advanced non-small cell lung cancer were treated with combination chemotherapy consisting of cis-diamminedichloro platinum (II), Adriamycin, 5-fluorouracil, methotrexate and vincristine. The objective response rate was 37.1% and the overall median survival 52.8 weeks. Notable toxicity was infrequent and reversible. Although the investigators have obtained higher response rates with other platinum-based combination chemotherapies, the present regimen appears superior in that other regimens fail to yield superior survival times while consistently inducing more severe toxicity.

Cervical mosaic and an integrated pathophysiological approach to early cervical neoplasia.

The increasing concern for the early detection and treatment of cervical intraepithelial neoplasia (CIN) set up the basis for this study, which also considers some epidemiological factors which seem to be related to the genesis of an abnormal uterine cervical colposcopic pattern, the mosaic pattern. We have observed that women with a mosaic pattern show an increasing frequency of premalignant and/or malignant histologic changes up to 40 years of age which then falls abruptly. Sterility and hirsutism were frequent associations, these features suggesting an abnormal hormonal status. An association with infection by Gardnerella vaginalis (15.3%) was noted, and dysplasia increased in frequency to 53% when G. vaginalis was associated with mosaic. Also, 67.25% of women with mosaic showed other concomitant diseases of allergic, immunologic, or infectious type. Based upon these observations, and in an attempt to explain further interrelationships among several factors in the pathogenesis of CIN, an integrated hypothesis which may lead to new therapeutic avenues, both in the prevention and treatment of early cervical cancer, is advanced.