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Garber, Jeffrey

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Garber

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Garber, Jeffrey

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2011 - 20183

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Author's Publications: search.filters.isAuthorOfPublication.d26e9e91-9496-4967-ad57-c19393c2b2a1

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    Palladium-catalysed electrophilic aromatic C–H fluorination
    (Springer Nature, 2018) Yamamoto, Kumiko; Li, Jiakun; Garber, Jeffrey; Rolfes, Julian D.; Boursalian, Gregory B.; Borghs, Jannik C.; Genicot, Christophe; Jacq, Jérôme; van Gastel, Maurice; Neese, Frank; Ritter, Tobias
    Aryl fluorides are widely used in the pharmaceutical and agrochemical industries1,2, and recent advances have enabled their synthesis through the conversion of various functional groups. However, there is a lack of general methods for direct aromatic carbon–hydrogen (C–H) fluorination3. Conventional methods require the use of either strong fluorinating reagents, which are often unselective and difficult to handle, such as elemental fluorine, or less reactive reagents that attack only the most activated arenes, which reduces the substrate scope. A method for the direct fluorination of aromatic C–H bonds could facilitate access to fluorinated derivatives of functional molecules that would otherwise be difficult to produce. For example, drug candidates with improved properties, such as increased metabolic stability or better blood–brain-barrier penetration, may become available. Here we describe an approach to catalysis and the resulting development of an undirected, palladium-catalysed method for aromatic C–H fluorination using mild electrophilic fluorinating reagents. The reaction involves a mode of catalysis that is unusual in aromatic C–H functionalization because no organometallic intermediate is formed; instead, a reactive transition-metal-fluoride electrophile is generated catalytically for the fluorination of arenes that do not otherwise react with mild fluorinating reagents. The scope and functional-group tolerance of this reaction could provide access to functional fluorinated molecules in pharmaceutical and agrochemical development that would otherwise not be readily accessible.
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    Long-term, treatment-free survival in select patients with distant metastatic papillary thyroid cancer
    (Bioscientifica Ltd, 2014) Kwong, Norra; Marqusee, Ellen; Gordon, Michael; Larsen, P Reed; Garber, Jeffrey; Kim, Matthew; Alexander, Erik
    Well-differentiated thyroid carcinoma (WDTC) generally has a favorable prognosis. However, patients with distant metastatic disease experience progression of disease with a higher mortality. A subset of patients not previously described may challenge the conventional dogma regarding the progressive nature of all metastatic WDTC. Through analysis of our database, we identified patients with distant metastatic WDTC and persistent, minimally progressive disease. In all patients, persistent metastatic disease was confirmed via tissue biopsy, abnormal PET scan, and/or biochemical elevations in thyroglobulin or antibody levels. Progression of disease was monitored clinically and with repeat imaging. We describe five patients with WDTC and pulmonary metastases, aged 8–43 years at diagnosis. All patients underwent initial surgery and radioactive iodine (RAI) ablation, with some receiving multiple treatments. Persistent pulmonary metastatic disease was confirmed over decades (mean 22 years, range 8–42 years) with minimal progression despite no further treatment beyond thyroid hormone suppression. Persistent disease was biopsy-proven in all patients at a mean of 9.6 years from last RAI treatment. All patients had elevated thyroglobulin or anti-thyroglobulin antibody levels, while three demonstrated metabolically active disease with positive FDG uptake on PET scan, and one patient with persistent radioactive iodine avid pulmonary metastasis 36 years after her last RAI treatment. This case series demonstrates that some patients with distant metastases, even if metabolically active and radioactive iodine resistant, remain stable for decades without further treatment. Clinical awareness of such patients and continual reassessment of disease risk following initial therapy are crucial as aggressive treatment may not be necessary.
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    Factors Determining the Persistence or Recurrence of Well-Differentiated Thyroid Cancer Treated by Thyroidectomy and/or Radioiodine in the Boston, Massachusetts Area: A Retrospective Chart Review
    (BioMed Central, 2011) Leung, Angela M.; Dave, Shalini; Lee, Stephanie L.; Campion, Francis; Garber, Jeffrey; Pearce, Elizabeth N.
    Objective: To assess predictors of well-differentiated thyroid cancer (WDTC) persistence/recurrence. Design: This was a retrospective chart review of thyroid carcinoma patients seen 1979-2007 in a Boston, Massachusetts-area multispecialty group. Of 1,025 patients, 431 met eligibility criteria. Cox proportional hazards models were used to assess predictors (gender, age, ethnicity, tumor size, surgical histology) of WDTC persistence/recurrence (elevated thyroglobulin levels with negative thyroglobulin-antibodies; or positive imaging). Local extension of disease and lymph node involvement could not be assessed. Results: Mean age at initial surgery (n = 431, 74% women, 79% Caucasian) was 45.8 \(\pm\) 13.5(SD) years. Mean tumor (papillary, 91%; follicular, 5%; Hurthle cell, 2%; \(\ge\)1 type, 2%) size was 2.5 \(\pm\) 1.6(SD) cm. Most tumors were unifocal (57%) and \(\ge\)1 cm (89%). Over 2,600 person-years of follow-up, persistence/recurrence occurred in 52 patients (12%) 4.3 years (median; range 0.2-23.2 years) after surgery. Gender, ethnicity, tumor size, multifocality, and histology were not predictive of persistence/recurrence, while older age was predictive in some models. Conclusions: In WDTC patients treated by total and near total thyroidectomy and radioiodine and analyzed without consideration of local, locoregional, and distant extent of disease, neither size of tumor nor male gender contribute to disease persistence/recurrence. Age at diagnosis seems to have some positive prognostic value even if only patients older than 21 years at diagnosis are considered. Due to the rare occurrence of follicular (also oxyphilic) histotype, this conclusion refers mainly to patients with papillary thyroid cancer.