Combination Treatment of Intratumoral Vidutolimod, Radiosurgery, Nivolumab, and Ipilimumab for Microsatellite Stable Colorectal Carcinoma With Liver Metastases.

Introduction: Microsatellite stable metastatic colorectal cancer (MSS mCRC) is largely refractory to immune checkpoint inhibition. We hypothesized that a combination of intratumoral TLR9 agonist, radiosurgery and dual PD-1 and CTLA-4 blockade would induce a local focus of immune stimulation, evoking a systemic immune response.

Patients And Methods: In this phase I single-institution study, patients with MSS mCRC were treated with a priming dose of s.

Process of drug registration in Israel: the correlation between the number of discussions within the Ministry of Health and postapproval variations by EMA and/or FDA.

Objectives: US FDA and EMA allow facilitated regulatory pathways to expedite access to new treatments. Limited supportive data may result in major postapproval variations. In Israel, partly relying on Food and Drug Administration (FDA) and European Medicines Agency (EMA), clinical data are reviewed independently by the Advisory Committee of Drug Registration (ACDR).

Single-Fraction Celiac Plexus Radiosurgery: A Preliminary Proof-of-Concept Phase 2 Clinical Trial.

Background: Refractory epigastric/midback pain is associated with locally advanced abdominal malignancies, especially pancreatic cancer. The pain is caused by tumor infiltration of the celiac plexus, a nerve network attached to the abdominal aorta. Contemporary palliative approaches are often inadequate.

[GERIATRIC ONCOLOGY - CANCER TREATMENT IN OLDER ADULTS AND OLDEST-OLD].

Introduction: Geriatric oncology is the clinical field of cancer treatment in older adults (above 65 years) and in the oldest-old (above 80 years). As age is the most significant risk factor for cancer, and with the aging of the population, there is a vast increase in the number of older cancer patients.

Background: The cases highlight the unique challenges in geriatric oncology: disease goals may differ; treatment toxicities are higher; the extensive use of prescription medication increases the chances of harmful drug-drug interactions; finally, older adults have unique psychosocial needs.

KRAS Status as a Predictor of Chemotherapy Activity in Patients With Metastatic Colorectal Cancer.

Background: KRAS mutations occur in 40% of colorectal cancers (CRCs), affecting the efficacy of agents targeting the epidermal growth factor receptor. However, the effect of KRAS mutation status on the activity of non-epidermal growth factor receptor-targeting chemotherapy has not been fully elucidated. The aim of the present study is to evaluate the effect of KRAS status on the activity of different chemotherapeutic regimens.

Topical doxycycline foam 4% for prophylactic management of epidermal growth factor receptor inhibitor skin toxicity: an exploratory phase 2, randomized, double-blind clinical study.

Purpose: Acneiform rash, a common toxicity of epidermal growth factor receptor inhibitors (EGFRIs), can cause patient discomfort, warranting changes in treatment. This study investigated the safety, tolerability, and efficacy of a novel doxycycline foam, FDX104 4%, for managing EGFRI-related skin toxicity.

Methods: This was an exploratory phase 2, randomized, double-blind, placebo-controlled study.

D1 versus D2 Gastrectomy for Gastric Adenocarcinoma.

Background: Despite the ongoing decrease in the incidence of gastric cancer, this disease is still a major cause of death. It is still debatable whether D2 lymphadenectomy improves survival and whether this procedure should be performed routinely or selectively.

Objectives: To compare the pathological and short-term results following radical D2-type gastric resection and lymphadenectomy versus the more limited D1 type resection and lymphadenectomy.

A comparative study on two different pathological methods to retrieve lymph nodes following gastrectomy.

Background: The number of lymph nodes harvested during gastrectomy depends on the extension of lymphadenectomy and the method of lymph node retrieval.

Aim: The objective of this study was to evaluate two methods of lymph node retrieval in specimens of gastric cancer.

Methods: The number of lymph nodes was compared using two different techniques.

Phase I clinical trial of Exherin (ADH-1) in patients with advanced solid tumors.

Unlabelled: ADH-1 (Exherin™) is a pentapeptide, which competitively inhibits N-cadherin, resulting in vascular disruptive effect of tumor vasculature in preclinical models. This study was designed to assess the toxicity of ADH-1 and to determine the maximal tolerated dose (MTD).

Patients And Methods: Adult patients with advanced measurable solid tumors were stratified according to their tumor N-cadherin status.

Stage-dependent differential expression of microRNAs in colorectal cancer: potential role as markers of metastatic disease.

MicroRNAs (miRs) are short non-coding RNAs that bind complementary sequences in mRNA resulting in translation repression and/or mRNA degradation. We investigated expression of the reported metastasis-associated miRs-335, 206, 135a, 146a, 146b, 10b, 21, let7a and let7b in normal mucosa, non-metastatic and metastatic colorectal cancer (CRC). Expression of target miRs in micro-dissected paraffin embedded tissues was evaluated in 15 primary tumours with adjacent normal tissue from patients that were disease-free at 4 years (cohort A) and 19 paired primary tumours with corresponding liver metastases (cohort B) by quantitative real-time PCR.

ADH-1 in the treatment of metastatic adrenocortical carcinoma--case report.

Adrenocortical Carcinoma (ACC) is rare with an annual incidence of 0.5-2 cases per million worldwide. Some ACC tumors over express N-cadherin, which correlates with metastatic potential.

The role of the epidermal growth factor receptor in the mechanism and treatment of colorectal cancer.

The epidermal growth factor receptor is a member of the receptor tyrosine kinase family whose members play a critical role in oncogenesis. In particular, EGFR has been shown to participate in colon cancer development. Due to its role in the progression of colon cancer, EGFR has become an attractive target for therapy and two different classes of biologic agents have been evaluated: the EGFR monoclonal antibodies and the tyrosine kinase inhibitors.

EGFR expression variance in paired colorectal cancer primary and metastatic tumors.

Background: Previous studies indicate that drugs targeting the Epidermal Growth Factor Receptor (EGFR) signaling pathways can induce objective responses, prolong time to progression and improve survival of patients with metastatic colorectal cancer (mCRC). EGFR expression in the primary tumour may not predict response to these agents and data is conflicting regarding the correlation of EGFR expression in the primary tumour with the metastatic site. In other tumour sites, the presence of EGFR mutations was associated with efficacy in a subset of patients.

A similar cell-specific pattern of HOXA methylation in normal and in cancer tissues.

HOX genes are developmental genes that determine anterior-posterior embryonic pattern and govern the process of differentiation. Inappropriate expression of HOX genes has been implicated in developmental abnormalities and hematopoietic malignancies. In addition, HOX genes silencing by DNA methylation has been reported in cancers and related to disease aggressiveness and outcome.

Epistaxis during treatment with paclitaxel.

The purpose of this study was to determine the incidence and severity of epistaxis in patients treated with paclitaxel. Patients who were treated with paclitaxel filled a questionnaire regarding their general health, medications and incidents of epistaxis. Relevant clinical information was obtained from the patients' charts.

Neoadjuvant chemohormonal therapy in poor-prognosis localized prostate cancer.

Objectives: To conduct a trial of neoadjuvant chemohormonal therapy and radical prostatectomy for patients with poor-prognosis localized prostate cancer (prostate-specific antigen [PSA] value 20 ng/mL or greater, Gleason score 8 or higher, and clinical stage T2c or greater), who are at high risk for local and systemic relapse.

Methods: Complete androgen blockage and four cycles of docetaxel (70 mg/m2) on day 2 and estramustine (280 mg three times daily) on days 1 to 5 every 21 days were given to 22 patients before radical prostatectomy and nerve preservation.

Results: Patient characteristics, as median (range), were as follows: age 61 (49 to 70) years, PSA value 21.

Progression after docetaxel-based chemotherapy in androgen-independent prostate cancer.

Objective: To assess the clinical pattern of progression and prostate-specific antigen doubling time (PSA-DT) after exposure to docetaxel-based chemotherapy in patients with androgen-independent prostate cancer (AIPC).

Patients And Methods: Fifty-five patients received docetaxel-based chemotherapy; data were collected retrospectively from three different departments. Progression was known in 44 (79%) and the PSA-DT was available in 33 patients.

[Taxotere-based chemotherapy in androgen-independent prostate cancer].

Objective: Taxotere-based chemotherapy is the only approach which has recently demonstrated prolongation of survival in patients with androgen-independent prostate cancer. This article presents our experience with this therapy.

Methods: Since August 1999 we treated 49 patients with Taxotere/Estramustine or Taxotere/Prednisone combinations.

Extracellular signal-regulated kinase 1c (ERK1c), a novel 42-kilodalton ERK, demonstrates unique modes of regulation, localization, and function.

Extracellular signal-regulated kinases (ERKs) are signaling molecules that regulate many cellular processes. We have previously identified an alternatively spliced 46-kDa form of ERK1 that is expressed in rats and mice and named ERK1b. Here we report that the same splicing event in humans and monkeys causes, due to sequence differences in the inserted introns, the production of an ERK isoform that migrates together with the 42-kDa ERK2.