The mediators and cellular effectors of inflammation are important constituents of the local environment of tumours. In some types of cancer, inflammatory conditions are present before a malignant change occurs. Conversely, in other types of cancer, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumours. Regardless of its origin, 'smouldering' inflammation in the tumour microenvironment has many tumour-promoting effects. It aids in the proliferation and survival of malignant cells, promotes angiogenesis and metastasis, subverts adaptive immune responses, and alters responses to hormones and chemotherapeutic agents. The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.

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Cancer-related inflammation.

http://aiocm.org/member/Immunity,%20Inflammation,%20and%20Cancer.pdf

Immunity, Inflammation, and Cancer

Macrophage Diversity Enhances Tumor Progression and Metastasis

Flavonoids are a class of secondary plant phenolics with significant antioxidant and chelating properties. In the human diet, they are most concentrated in fruits, vegetables, wines, teas and cocoa. Their cardioprotective effects stem from the ability to inhibit lipid peroxidation, chelate redox-active metals, and attenuate other processes involving reactive oxygen species. Flavonoids occur in foods primarily as glycosides and polymers that are degraded to variable extents in the digestive tract. Although metabolism of these compounds remains elusive, enteric absorption occurs sufficiently to reduce plasma indices of oxidant status. The propensity of a flavonoid to inhibit free-radical mediated events is governed by its chemical structure. Since these compounds are based on the flavan nucleus, the number, positions, and types of substitutions influence radical scavenging and chelating activity. The diversity and multiple mechanisms of flavonoid action, together with the numerous methods of initiation, detection and measurement of oxidative processes in vitro and in vivo offer plausible explanations for existing discrepancies in structure-activity relationships. Despite some inconsistent lines of evidence, several structure-activity relationships are well established in vitro. Multiple hydroxyl groups confer upon the molecule substantial antioxidant, chelating and prooxidant activity. Methoxy groups introduce unfavorable steric effects and increase lipophilicity and membrane partitioning. A double bond and carbonyl function in the heterocycle or polymerization of the nuclear structure increases activity by affording a more stable flavonoid radical through conjugation and electron delocalization. Further investigation of the metabolism of these phytochemicals is justified to extend structure-activity relationships (SAR) to preventive and therapeutic nutritional strategies.

Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships.

Metastasis is a multistage process that requires cancer cells to escape from the primary tumour, survive in the circulation, seed at distant sites and grow. Each of these processes involves rate-limiting steps that are influenced by non-malignant cells of the tumour microenvironment. Many of these cells are derived from the bone marrow, particularly the myeloid lineage, and are recruited by cancer cells to enhance their survival, growth, invasion and dissemination. This Review describes experimental data demonstrating the role of the microenvironment in metastasis, identifies areas for future research and suggests possible new therapeutic avenues.

/pdf/microenvironmental-regulation-of-metastasis-49v9l5nr6y.pdf

Microenvironmental regulation of metastasis

Phase II study of protracted irinotecan infusion and a low-dose cisplatin for metastatic gastric cancer

Immunological properties of Fc receptor on lymphocytes. 7. Suppression of mixed lymphocyte reaction by Fc receptor-bearing splenic lymphocytes.

Dehydropyrimidine dehydrogenase (DPD) is the initial key enzyme in the regulation of 5-fluorouracil catabolism and thus controls availability of 5-fluorouracil for anabolism. Modulation of DPD activity may increase the antitumor effect and avoid toxic side effects in 5-fluorouracil-based chemotherapy. We measured DPD activity in peripheral blood mononuclear cells from cancer patients and simultaneously monitored intracellular glutathione (GSH) and plasma GSH levels. There was a significant linear relationship between DPD activity and intracellular GSH levels in peripheral blood mononuclear cells obtained from cancer patients. Suppression of intracellular GSH level by buthionine sulfoximine decreased DPD activity, while enhancement of intracellular GSH level by 2-mercaptoethanol increased DPD activity. This study indicated that alteration of intracellular GSH concentration may modulate DPD activity.

Modulation of intracellular glutathione concentration alters dehydropyrimidine dehydrogenase activity in peripheral blood mononuclear cells.

9 Background: The Z9001 study revealed adjuvant imatinib for 1 year significantly improved RFS in GIST patients (pts). The SSGXVIII study compared 3 years with 1 year of adjuvant imatinib for high risk GIST pts, but there was no study to evaluate shorter period of imatinib administration than 1 year. We conducted a randomized phase II study to compare 6 months (6-mo) with 12 months (12-mo) adjuvant imatinib for intermediate or high risk GIST pts. Methods: Inclusion criteria included ECOG-PS of 0 or 1, age between 20 and 79 years, and primary KIT-positive GIST with intermediate or high risk according to the Fletcher criteria. Pts were randomized assigned to the 6-mo or 12-mo treatment of imatinib 400 mg/day after complete resection. The primary endpoint was recurrence-free survival (RFS). The study was designed as a randomized screening trial to evaluate non-inferiority with margin of hazard ratio 1.67, 1-sided alpha 0.2 and power 0.8. Results: Ninety-two pts were randomly allocated the 6-mo group (n=45) o...

Arimichi Takabayashi

Papers

Phase II study of protracted irinotecan infusion and a low-dose cisplatin for metastatic gastric cancer

Immunological properties of Fc receptor on lymphocytes. 7. Suppression of mixed lymphocyte reaction by Fc receptor-bearing splenic lymphocytes.

Modulation of intracellular glutathione concentration alters dehydropyrimidine dehydrogenase activity in peripheral blood mononuclear cells.

Randomized phase II study of 6 versus 12 months of adjuvant imatinib for patients with intermediate- or high-risk GIST.

Two cases of SIADH in patients with gastrointestinal cancer possibly induced by CDDP in FP chemotherapy